MATN3

Functionⁱ

Major component of the extracellular matrix of cartilage and may play a role in the formation of extracellular filamentous networks.

GO - Molecular functionⁱ

calcium ion binding Source: InterPro
extracellular matrix structural constituent
Source: ProtInc
Traceable author statementⁱ
- 9350998

GO - Biological processⁱ

extracellular matrix organization Source: Reactome
skeletal system development
Source: ProtInc
Traceable author statementⁱ
- 9350998

Complete GO annotation...

Enzyme and pathway databases

Reactomeⁱ	R-HSA-3000178. ECM proteoglycans.

Reactomeⁱ

R-HSA-3000178. ECM proteoglycans.

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Matrilin-3
Gene namesⁱ	Name:MATN3
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 2

Organism-specific databases

HGNCⁱ	HGNC:6909. MATN3.

HGNCⁱ

HGNC:6909. MATN3.

Subcellular locationⁱ

Secreted

GO - Cellular componentⁱ

extracellular region Source: Reactome
proteinaceous extracellular matrix
Source: ProtInc
Traceable author statementⁱ
- 9350998

Complete GO annotation...

Keywords - Cellular componentⁱ

Secreted

Pathology & Biotechⁱ

Involvement in diseaseⁱ

Multiple epiphyseal dysplasia 5 (EDM5)7 Publications
Manual assertion based on experiment inⁱ
Ref.10
"Mutations in the region encoding the von Willebrand factor A domain of matrilin-3 are associated with multiple epiphyseal dysplasia."
Chapman K.L., Mortier G.R., Chapman K., Loughlin J., Grant M.E., Briggs M.D.
Nat. Genet. 28:393-396(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS EDM5 TRP-121 AND ASP-194.
Ref.12
"Familial multiple epiphyseal dysplasia due to a matrilin-3 mutation: further delineation of the phenotype including 40 years follow-up."
Mostert A.K., Dijkstra P.F., Jansen B.R.H., van Horn J.R., de Graaf B., Heutink P., Lindhout D.
Am. J. Med. Genet. A 120:490-497(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT EDM5 PRO-128.
Ref.13
"Novel and recurrent mutations clustered in the von Willebrand factor A domain of MATN3 in multiple epiphyseal dysplasia."
Mabuchi A., Haga N., Maeda K., Nakashima E., Manabe N., Hiraoka H., Kitoh H., Kosaki R., Nishimura G., Ohashi H., Ikegawa S.
Hum. Mutat. 24:439-440(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS EDM5 SER-105; MET-120 AND TRP-121, VARIANTS SER-11; LYS-252 AND MET-303.
Ref.14
"Missense mutations in the beta strands of the single A-domain of matrilin-3 result in multiple epiphyseal dysplasia."
Jackson G.C., Barker F.S., Jakkula E., Czarny-Ratajczak M., Maekitie O., Cole W.G., Wright M.J., Smithson S.F., Suri M., Rogala P., Mortier G.R., Baldock C., Wallace A., Elles R., Ala-Kokko L., Briggs M.D.
J. Med. Genet. 41:52-59(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS EDM5 MET-120; TRP-121; LYS-134; ASN-192 AND ASP-219, VARIANTS LYS-252 AND MET-303.
Ref.16
"Mutation in the von Willebrand factor-A domain is not a prerequisite for the MATN3 mutation in multiple epiphyseal dysplasia."
Maeda K., Nakashima E., Horikoshi T., Mabuchi A., Ikegawa S.
Am. J. Med. Genet. A 136:285-286(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT EDM5 HIS-70.
Ref.17
"Multiple epiphyseal dysplasia mutations in MATN3 cause misfolding of the A-domain and prevent secretion of mutant matrilin-3."
Cotterill S.L., Jackson G.C., Leighton M.P., Wagener R., Maekitie O., Cole W.G., Briggs M.D.
Hum. Mutat. 26:557-565(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS EDM5 TRP-121; LYS-195 AND ASN-218, VARIANT LYS-252, CHARACTERIZATION OF VARIANTS MET-120; TRP-121; LYS-134; ASN-192; ASP-194 AND ASP-219, CHARACTERIZATION OF VARIANT LYS-252.
Ref.18
"Pseudoachondroplasia and multiple epiphyseal dysplasia: A 7-year comprehensive analysis of the known disease genes identify novel and recurrent mutations and provides an accurate assessment of their relative contribution."
Jackson G.C., Mittaz-Crettol L., Taylor J.A., Mortier G.R., Spranger J., Zabel B., Le Merrer M., Cormier-Daire V., Hall C.M., Offiah A., Wright M.J., Savarirayan R., Nishimura G., Ramsden S.C., Elles R., Bonafe L., Superti-Furga A., Unger S., Zankl A., Briggs M.D.
Hum. Mutat. 33:144-157(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS EDM5 MET-120; TRP-121; 171-ASP--VAL-176 DEL; ASP-173; LYS-195; PRO-209; ASN-218; ASP-219; ASN-231 AND MET-245.

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA generalized skeletal dysplasia associated with significant morbidity. Joint pain, joint deformity, waddling gait, and short stature are the main clinical signs and symptoms. Radiological examination of the skeleton shows delayed, irregular mineralization of the epiphyseal ossification centers and of the centers of the carpal and tarsal bones. Multiple epiphyseal dysplasia is broadly categorized into the more severe Fairbank and the milder Ribbing types. The Fairbank type is characterized by shortness of stature, short and stubby fingers, small epiphyses in several joints, including the knee, ankle, hand, and hip. The Ribbing type is confined predominantly to the hip joints and is characterized by hands that are normal and stature that is normal or near-normal. Multiple epiphyseal dysplasia type 5 is relatively mild and clinically variable. It is primarily characterized by delayed and irregular ossification of the epiphyses and early-onset osteoarthritis.

See also OMIM:607078

Feature key	Position(s)	Length	Description	Feature identifier
Natural variantⁱ	70 – 70	1	R → H in EDM5. 1 Publication Manual assertion based on experiment inⁱ Ref.16 "Mutation in the von Willebrand factor-A domain is not a prerequisite for the MATN3 mutation in multiple epiphyseal dysplasia." Maeda K., Nakashima E., Horikoshi T., Mabuchi A., Ikegawa S. Am. J. Med. Genet. A 136:285-286(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT EDM5 HIS-70. Corresponds to variant rs104893640 [ dbSNP \| Ensembl ].	VAR_054807
Natural variantⁱ	105 – 105	1	F → S in EDM5. 1 Publication Manual assertion based on experiment inⁱ Ref.13 "Novel and recurrent mutations clustered in the von Willebrand factor A domain of MATN3 in multiple epiphyseal dysplasia." Mabuchi A., Haga N., Maeda K., Nakashima E., Manabe N., Hiraoka H., Kitoh H., Kosaki R., Nishimura G., Ohashi H., Ikegawa S. Hum. Mutat. 24:439-440(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 SER-105; MET-120 AND TRP-121, VARIANTS SER-11; LYS-252 AND MET-303.	VAR_020844
Natural variantⁱ	120 – 120	1	T → M in EDM5; retained and accumulates within the cell. 4 Publications Manual assertion based on experiment inⁱ Ref.13 "Novel and recurrent mutations clustered in the von Willebrand factor A domain of MATN3 in multiple epiphyseal dysplasia." Mabuchi A., Haga N., Maeda K., Nakashima E., Manabe N., Hiraoka H., Kitoh H., Kosaki R., Nishimura G., Ohashi H., Ikegawa S. Hum. Mutat. 24:439-440(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 SER-105; MET-120 AND TRP-121, VARIANTS SER-11; LYS-252 AND MET-303. Ref.14 "Missense mutations in the beta strands of the single A-domain of matrilin-3 result in multiple epiphyseal dysplasia." Jackson G.C., Barker F.S., Jakkula E., Czarny-Ratajczak M., Maekitie O., Cole W.G., Wright M.J., Smithson S.F., Suri M., Rogala P., Mortier G.R., Baldock C., Wallace A., Elles R., Ala-Kokko L., Briggs M.D. J. Med. Genet. 41:52-59(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 MET-120; TRP-121; LYS-134; ASN-192 AND ASP-219, VARIANTS LYS-252 AND MET-303. Ref.17 "Multiple epiphyseal dysplasia mutations in MATN3 cause misfolding of the A-domain and prevent secretion of mutant matrilin-3." Cotterill S.L., Jackson G.C., Leighton M.P., Wagener R., Maekitie O., Cole W.G., Briggs M.D. Hum. Mutat. 26:557-565(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 TRP-121; LYS-195 AND ASN-218, VARIANT LYS-252, CHARACTERIZATION OF VARIANTS MET-120; TRP-121; LYS-134; ASN-192; ASP-194 AND ASP-219, CHARACTERIZATION OF VARIANT LYS-252. Ref.18 "Pseudoachondroplasia and multiple epiphyseal dysplasia: A 7-year comprehensive analysis of the known disease genes identify novel and recurrent mutations and provides an accurate assessment of their relative contribution." Jackson G.C., Mittaz-Crettol L., Taylor J.A., Mortier G.R., Spranger J., Zabel B., Le Merrer M., Cormier-Daire V., Hall C.M., Offiah A., Wright M.J., Savarirayan R., Nishimura G., Ramsden S.C., Elles R., Bonafe L., Superti-Furga A., Unger S., Zankl A., Briggs M.D. Hum. Mutat. 33:144-157(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 MET-120; TRP-121; 171-ASP--VAL-176 DEL; ASP-173; LYS-195; PRO-209; ASN-218; ASP-219; ASN-231 AND MET-245. Corresponds to variant rs397515546 [ dbSNP \| Ensembl ].	VAR_019882
Natural variantⁱ	121 – 121	1	R → W in EDM5; retained and accumulates within the cell. 5 Publications Manual assertion based on experiment inⁱ Ref.10 "Mutations in the region encoding the von Willebrand factor A domain of matrilin-3 are associated with multiple epiphyseal dysplasia." Chapman K.L., Mortier G.R., Chapman K., Loughlin J., Grant M.E., Briggs M.D. Nat. Genet. 28:393-396(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 TRP-121 AND ASP-194. Ref.13 "Novel and recurrent mutations clustered in the von Willebrand factor A domain of MATN3 in multiple epiphyseal dysplasia." Mabuchi A., Haga N., Maeda K., Nakashima E., Manabe N., Hiraoka H., Kitoh H., Kosaki R., Nishimura G., Ohashi H., Ikegawa S. Hum. Mutat. 24:439-440(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 SER-105; MET-120 AND TRP-121, VARIANTS SER-11; LYS-252 AND MET-303. Ref.14 "Missense mutations in the beta strands of the single A-domain of matrilin-3 result in multiple epiphyseal dysplasia." Jackson G.C., Barker F.S., Jakkula E., Czarny-Ratajczak M., Maekitie O., Cole W.G., Wright M.J., Smithson S.F., Suri M., Rogala P., Mortier G.R., Baldock C., Wallace A., Elles R., Ala-Kokko L., Briggs M.D. J. Med. Genet. 41:52-59(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 MET-120; TRP-121; LYS-134; ASN-192 AND ASP-219, VARIANTS LYS-252 AND MET-303. Ref.17 "Multiple epiphyseal dysplasia mutations in MATN3 cause misfolding of the A-domain and prevent secretion of mutant matrilin-3." Cotterill S.L., Jackson G.C., Leighton M.P., Wagener R., Maekitie O., Cole W.G., Briggs M.D. Hum. Mutat. 26:557-565(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 TRP-121; LYS-195 AND ASN-218, VARIANT LYS-252, CHARACTERIZATION OF VARIANTS MET-120; TRP-121; LYS-134; ASN-192; ASP-194 AND ASP-219, CHARACTERIZATION OF VARIANT LYS-252. Ref.18 "Pseudoachondroplasia and multiple epiphyseal dysplasia: A 7-year comprehensive analysis of the known disease genes identify novel and recurrent mutations and provides an accurate assessment of their relative contribution." Jackson G.C., Mittaz-Crettol L., Taylor J.A., Mortier G.R., Spranger J., Zabel B., Le Merrer M., Cormier-Daire V., Hall C.M., Offiah A., Wright M.J., Savarirayan R., Nishimura G., Ramsden S.C., Elles R., Bonafe L., Superti-Furga A., Unger S., Zankl A., Briggs M.D. Hum. Mutat. 33:144-157(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 MET-120; TRP-121; 171-ASP--VAL-176 DEL; ASP-173; LYS-195; PRO-209; ASN-218; ASP-219; ASN-231 AND MET-245. Corresponds to variant rs104893637 [ dbSNP \| Ensembl ].	VAR_013691
Natural variantⁱ	128 – 128	1	A → P in EDM5; bilateral hereditary microepiphyseal dysplasia. 1 Publication Manual assertion based on experiment inⁱ Ref.12 "Familial multiple epiphyseal dysplasia due to a matrilin-3 mutation: further delineation of the phenotype including 40 years follow-up." Mostert A.K., Dijkstra P.F., Jansen B.R.H., van Horn J.R., de Graaf B., Heutink P., Lindhout D. Am. J. Med. Genet. A 120:490-497(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT EDM5 PRO-128. Corresponds to variant rs104893641 [ dbSNP \| Ensembl ].	VAR_019883
Natural variantⁱ	134 – 134	1	E → K in EDM5; retained and accumulates within the cell. 2 Publications Manual assertion based on experiment inⁱ Ref.14 "Missense mutations in the beta strands of the single A-domain of matrilin-3 result in multiple epiphyseal dysplasia." Jackson G.C., Barker F.S., Jakkula E., Czarny-Ratajczak M., Maekitie O., Cole W.G., Wright M.J., Smithson S.F., Suri M., Rogala P., Mortier G.R., Baldock C., Wallace A., Elles R., Ala-Kokko L., Briggs M.D. J. Med. Genet. 41:52-59(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 MET-120; TRP-121; LYS-134; ASN-192 AND ASP-219, VARIANTS LYS-252 AND MET-303. Ref.17 "Multiple epiphyseal dysplasia mutations in MATN3 cause misfolding of the A-domain and prevent secretion of mutant matrilin-3." Cotterill S.L., Jackson G.C., Leighton M.P., Wagener R., Maekitie O., Cole W.G., Briggs M.D. Hum. Mutat. 26:557-565(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 TRP-121; LYS-195 AND ASN-218, VARIANT LYS-252, CHARACTERIZATION OF VARIANTS MET-120; TRP-121; LYS-134; ASN-192; ASP-194 AND ASP-219, CHARACTERIZATION OF VARIANT LYS-252.	VAR_019884
Natural variantⁱ	171 – 176	6	Missing in EDM5. 1 Publication Manual assertion based on experiment inⁱ Ref.18 "Pseudoachondroplasia and multiple epiphyseal dysplasia: A 7-year comprehensive analysis of the known disease genes identify novel and recurrent mutations and provides an accurate assessment of their relative contribution." Jackson G.C., Mittaz-Crettol L., Taylor J.A., Mortier G.R., Spranger J., Zabel B., Le Merrer M., Cormier-Daire V., Hall C.M., Offiah A., Wright M.J., Savarirayan R., Nishimura G., Ramsden S.C., Elles R., Bonafe L., Superti-Furga A., Unger S., Zankl A., Briggs M.D. Hum. Mutat. 33:144-157(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 MET-120; TRP-121; 171-ASP--VAL-176 DEL; ASP-173; LYS-195; PRO-209; ASN-218; ASP-219; ASN-231 AND MET-245.	VAR_066830
Natural variantⁱ	173 – 173	1	A → D in EDM5. 1 Publication Manual assertion based on experiment inⁱ Ref.18 "Pseudoachondroplasia and multiple epiphyseal dysplasia: A 7-year comprehensive analysis of the known disease genes identify novel and recurrent mutations and provides an accurate assessment of their relative contribution." Jackson G.C., Mittaz-Crettol L., Taylor J.A., Mortier G.R., Spranger J., Zabel B., Le Merrer M., Cormier-Daire V., Hall C.M., Offiah A., Wright M.J., Savarirayan R., Nishimura G., Ramsden S.C., Elles R., Bonafe L., Superti-Furga A., Unger S., Zankl A., Briggs M.D. Hum. Mutat. 33:144-157(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 MET-120; TRP-121; 171-ASP--VAL-176 DEL; ASP-173; LYS-195; PRO-209; ASN-218; ASP-219; ASN-231 AND MET-245.	VAR_066831
Natural variantⁱ	192 – 192	1	I → N in EDM5; retained and accumulates within the cell. 2 Publications Manual assertion based on experiment inⁱ Ref.14 "Missense mutations in the beta strands of the single A-domain of matrilin-3 result in multiple epiphyseal dysplasia." Jackson G.C., Barker F.S., Jakkula E., Czarny-Ratajczak M., Maekitie O., Cole W.G., Wright M.J., Smithson S.F., Suri M., Rogala P., Mortier G.R., Baldock C., Wallace A., Elles R., Ala-Kokko L., Briggs M.D. J. Med. Genet. 41:52-59(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 MET-120; TRP-121; LYS-134; ASN-192 AND ASP-219, VARIANTS LYS-252 AND MET-303. Ref.17 "Multiple epiphyseal dysplasia mutations in MATN3 cause misfolding of the A-domain and prevent secretion of mutant matrilin-3." Cotterill S.L., Jackson G.C., Leighton M.P., Wagener R., Maekitie O., Cole W.G., Briggs M.D. Hum. Mutat. 26:557-565(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 TRP-121; LYS-195 AND ASN-218, VARIANT LYS-252, CHARACTERIZATION OF VARIANTS MET-120; TRP-121; LYS-134; ASN-192; ASP-194 AND ASP-219, CHARACTERIZATION OF VARIANT LYS-252.	VAR_019885
Natural variantⁱ	194 – 194	1	V → D in EDM5; retained and accumulates within the cell. 2 Publications Manual assertion based on experiment inⁱ Ref.10 "Mutations in the region encoding the von Willebrand factor A domain of matrilin-3 are associated with multiple epiphyseal dysplasia." Chapman K.L., Mortier G.R., Chapman K., Loughlin J., Grant M.E., Briggs M.D. Nat. Genet. 28:393-396(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 TRP-121 AND ASP-194. Ref.17 "Multiple epiphyseal dysplasia mutations in MATN3 cause misfolding of the A-domain and prevent secretion of mutant matrilin-3." Cotterill S.L., Jackson G.C., Leighton M.P., Wagener R., Maekitie O., Cole W.G., Briggs M.D. Hum. Mutat. 26:557-565(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 TRP-121; LYS-195 AND ASN-218, VARIANT LYS-252, CHARACTERIZATION OF VARIANTS MET-120; TRP-121; LYS-134; ASN-192; ASP-194 AND ASP-219, CHARACTERIZATION OF VARIANT LYS-252. Corresponds to variant rs104893645 [ dbSNP \| Ensembl ].	VAR_013692
Natural variantⁱ	195 – 195	1	T → K in EDM5. 2 Publications Manual assertion based on experiment inⁱ Ref.17 "Multiple epiphyseal dysplasia mutations in MATN3 cause misfolding of the A-domain and prevent secretion of mutant matrilin-3." Cotterill S.L., Jackson G.C., Leighton M.P., Wagener R., Maekitie O., Cole W.G., Briggs M.D. Hum. Mutat. 26:557-565(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 TRP-121; LYS-195 AND ASN-218, VARIANT LYS-252, CHARACTERIZATION OF VARIANTS MET-120; TRP-121; LYS-134; ASN-192; ASP-194 AND ASP-219, CHARACTERIZATION OF VARIANT LYS-252. Ref.18 "Pseudoachondroplasia and multiple epiphyseal dysplasia: A 7-year comprehensive analysis of the known disease genes identify novel and recurrent mutations and provides an accurate assessment of their relative contribution." Jackson G.C., Mittaz-Crettol L., Taylor J.A., Mortier G.R., Spranger J., Zabel B., Le Merrer M., Cormier-Daire V., Hall C.M., Offiah A., Wright M.J., Savarirayan R., Nishimura G., Ramsden S.C., Elles R., Bonafe L., Superti-Furga A., Unger S., Zankl A., Briggs M.D. Hum. Mutat. 33:144-157(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 MET-120; TRP-121; 171-ASP--VAL-176 DEL; ASP-173; LYS-195; PRO-209; ASN-218; ASP-219; ASN-231 AND MET-245.	VAR_054808
Natural variantⁱ	209 – 209	1	R → P in EDM5. 1 Publication Manual assertion based on experiment inⁱ Ref.18 "Pseudoachondroplasia and multiple epiphyseal dysplasia: A 7-year comprehensive analysis of the known disease genes identify novel and recurrent mutations and provides an accurate assessment of their relative contribution." Jackson G.C., Mittaz-Crettol L., Taylor J.A., Mortier G.R., Spranger J., Zabel B., Le Merrer M., Cormier-Daire V., Hall C.M., Offiah A., Wright M.J., Savarirayan R., Nishimura G., Ramsden S.C., Elles R., Bonafe L., Superti-Furga A., Unger S., Zankl A., Briggs M.D. Hum. Mutat. 33:144-157(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 MET-120; TRP-121; 171-ASP--VAL-176 DEL; ASP-173; LYS-195; PRO-209; ASN-218; ASP-219; ASN-231 AND MET-245. Corresponds to variant rs749845872 [ dbSNP \| Ensembl ].	VAR_066832
Natural variantⁱ	218 – 218	1	Y → N in EDM5. 2 Publications Manual assertion based on experiment inⁱ Ref.17 "Multiple epiphyseal dysplasia mutations in MATN3 cause misfolding of the A-domain and prevent secretion of mutant matrilin-3." Cotterill S.L., Jackson G.C., Leighton M.P., Wagener R., Maekitie O., Cole W.G., Briggs M.D. Hum. Mutat. 26:557-565(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 TRP-121; LYS-195 AND ASN-218, VARIANT LYS-252, CHARACTERIZATION OF VARIANTS MET-120; TRP-121; LYS-134; ASN-192; ASP-194 AND ASP-219, CHARACTERIZATION OF VARIANT LYS-252. Ref.18 "Pseudoachondroplasia and multiple epiphyseal dysplasia: A 7-year comprehensive analysis of the known disease genes identify novel and recurrent mutations and provides an accurate assessment of their relative contribution." Jackson G.C., Mittaz-Crettol L., Taylor J.A., Mortier G.R., Spranger J., Zabel B., Le Merrer M., Cormier-Daire V., Hall C.M., Offiah A., Wright M.J., Savarirayan R., Nishimura G., Ramsden S.C., Elles R., Bonafe L., Superti-Furga A., Unger S., Zankl A., Briggs M.D. Hum. Mutat. 33:144-157(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 MET-120; TRP-121; 171-ASP--VAL-176 DEL; ASP-173; LYS-195; PRO-209; ASN-218; ASP-219; ASN-231 AND MET-245.	VAR_054809
Natural variantⁱ	219 – 219	1	A → D in EDM5; retained and accumulates within the cell. 3 Publications Manual assertion based on experiment inⁱ Ref.14 "Missense mutations in the beta strands of the single A-domain of matrilin-3 result in multiple epiphyseal dysplasia." Jackson G.C., Barker F.S., Jakkula E., Czarny-Ratajczak M., Maekitie O., Cole W.G., Wright M.J., Smithson S.F., Suri M., Rogala P., Mortier G.R., Baldock C., Wallace A., Elles R., Ala-Kokko L., Briggs M.D. J. Med. Genet. 41:52-59(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 MET-120; TRP-121; LYS-134; ASN-192 AND ASP-219, VARIANTS LYS-252 AND MET-303. Ref.17 "Multiple epiphyseal dysplasia mutations in MATN3 cause misfolding of the A-domain and prevent secretion of mutant matrilin-3." Cotterill S.L., Jackson G.C., Leighton M.P., Wagener R., Maekitie O., Cole W.G., Briggs M.D. Hum. Mutat. 26:557-565(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 TRP-121; LYS-195 AND ASN-218, VARIANT LYS-252, CHARACTERIZATION OF VARIANTS MET-120; TRP-121; LYS-134; ASN-192; ASP-194 AND ASP-219, CHARACTERIZATION OF VARIANT LYS-252. Ref.18 "Pseudoachondroplasia and multiple epiphyseal dysplasia: A 7-year comprehensive analysis of the known disease genes identify novel and recurrent mutations and provides an accurate assessment of their relative contribution." Jackson G.C., Mittaz-Crettol L., Taylor J.A., Mortier G.R., Spranger J., Zabel B., Le Merrer M., Cormier-Daire V., Hall C.M., Offiah A., Wright M.J., Savarirayan R., Nishimura G., Ramsden S.C., Elles R., Bonafe L., Superti-Furga A., Unger S., Zankl A., Briggs M.D. Hum. Mutat. 33:144-157(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 MET-120; TRP-121; 171-ASP--VAL-176 DEL; ASP-173; LYS-195; PRO-209; ASN-218; ASP-219; ASN-231 AND MET-245. Corresponds to variant rs28939677 [ dbSNP \| Ensembl ].	VAR_019886
Natural variantⁱ	231 – 231	1	K → N in EDM5. 1 Publication Manual assertion based on experiment inⁱ Ref.18 "Pseudoachondroplasia and multiple epiphyseal dysplasia: A 7-year comprehensive analysis of the known disease genes identify novel and recurrent mutations and provides an accurate assessment of their relative contribution." Jackson G.C., Mittaz-Crettol L., Taylor J.A., Mortier G.R., Spranger J., Zabel B., Le Merrer M., Cormier-Daire V., Hall C.M., Offiah A., Wright M.J., Savarirayan R., Nishimura G., Ramsden S.C., Elles R., Bonafe L., Superti-Furga A., Unger S., Zankl A., Briggs M.D. Hum. Mutat. 33:144-157(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 MET-120; TRP-121; 171-ASP--VAL-176 DEL; ASP-173; LYS-195; PRO-209; ASN-218; ASP-219; ASN-231 AND MET-245. Corresponds to variant rs773642745 [ dbSNP \| Ensembl ].	VAR_066833
Natural variantⁱ	245 – 245	1	V → M in EDM5. 1 Publication Manual assertion based on experiment inⁱ Ref.18 "Pseudoachondroplasia and multiple epiphyseal dysplasia: A 7-year comprehensive analysis of the known disease genes identify novel and recurrent mutations and provides an accurate assessment of their relative contribution." Jackson G.C., Mittaz-Crettol L., Taylor J.A., Mortier G.R., Spranger J., Zabel B., Le Merrer M., Cormier-Daire V., Hall C.M., Offiah A., Wright M.J., Savarirayan R., Nishimura G., Ramsden S.C., Elles R., Bonafe L., Superti-Furga A., Unger S., Zankl A., Briggs M.D. Hum. Mutat. 33:144-157(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 MET-120; TRP-121; 171-ASP--VAL-176 DEL; ASP-173; LYS-195; PRO-209; ASN-218; ASP-219; ASN-231 AND MET-245. Corresponds to variant rs182164052 [ dbSNP \| Ensembl ].	VAR_066834

Spondyloepimetaphyseal dysplasia MATN3-related (SEMD-MATN3)1 Publication
Manual assertion based on experiment inⁱ
Ref.15
"Spondylo-epi-metaphyseal dysplasia (SEMD) matrilin 3 type: homozygote matrilin 3 mutation in a novel form of SEMD."
Borochowitz Z.U., Scheffer D., Adir V., Dagoneau N., Munnich A., Cormier-Daire V.
J. Med. Genet. 41:366-372(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SEMD-MATN3 SER-304.

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA bone disease characterized by disproportionate early-onset dwarfism, bowing of the lower limbs, lumbar lordosis and normal hands. Skeletal abnormalities include short, wide and stocky long bones with severe epiphyseal and metaphyseal changes, hypoplastic iliac bones and flat, ovoid vertebral bodies.

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
Natural variantⁱ	304 – 304	1	C → S in SEMD-MATN3. 1 Publication Manual assertion based on experiment inⁱ Ref.15 "Spondylo-epi-metaphyseal dysplasia (SEMD) matrilin 3 type: homozygote matrilin 3 mutation in a novel form of SEMD." Borochowitz Z.U., Scheffer D., Adir V., Dagoneau N., Munnich A., Cormier-Daire V. J. Med. Genet. 41:366-372(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT SEMD-MATN3 SER-304. Corresponds to variant rs104893639 [ dbSNP \| Ensembl ].		VAR_019888

Osteoarthritis 2 (OS2)1 Publication
Manual assertion based on experiment inⁱ
Ref.11
"Genomewide scan for hand osteoarthritis: a novel mutation in matrilin-3."
Stefansson S.E., Jonsson H., Ingvarsson T., Manolescu I., Jonsson H.H., Olafsdottir G., Palsdottir E., Stefansdottir G., Sveinbjornsdottir G., Frigge M.L., Kong A., Gulcher J.R., Stefansson K.
Am. J. Hum. Genet. 72:1448-1459(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MET-303, INVOLVEMENT IN OS2.

Disease susceptibility is associated with variations affecting the gene represented in this entry.

Disease descriptionA degenerative disease of the joints characterized by degradation of the hyaline articular cartilage and remodeling of the subchondral bone with sclerosis. Clinical symptoms include pain and joint stiffness often leading to significant disability and joint replacement. In the hand, osteoarthritis can develop in the distal interphalangeal and the first carpometacarpal (base of thumb) and proximal interphalangeal joints. Patients with osteoarthritis may have one, a few, or all of these sites affected.

Keywords - Diseaseⁱ

Disease mutation, Dwarfism

Organism-specific databases

MalaCardsⁱ	MATN3.
MIMⁱ	140600. phenotype. 607078. phenotype. 608728. phenotype.
Orphanetⁱ	93311. Multiple epiphyseal dysplasia type 5. 156728. Spondyloepimetaphyseal dysplasia, matrilin-3 type.
PharmGKBⁱ	PA30652.

Polymorphism and mutation databases

BioMutaⁱ	MATN3.

BioMutaⁱ

MATN3.

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
Signal peptideⁱ	1 – 28	28	Sequence analysis			Add BLAST
Chainⁱ	29 – 486	458	Matrilin-3		PRO_0000007657	Add BLAST

Amino acid modifications

Feature key	Position(s)	Length	Description
Disulfide bondⁱ	268 ↔ 279		PROSITE-ProRule annotation Manual assertion according to rulesⁱ PROSITE-ProRule:PRU00076
Disulfide bondⁱ	275 ↔ 289		PROSITE-ProRule annotation Manual assertion according to rulesⁱ PROSITE-ProRule:PRU00076
Disulfide bondⁱ	291 ↔ 304		PROSITE-ProRule annotation Manual assertion according to rulesⁱ PROSITE-ProRule:PRU00076
Disulfide bondⁱ	310 ↔ 321		PROSITE-ProRule annotation Manual assertion according to rulesⁱ PROSITE-ProRule:PRU00076
Disulfide bondⁱ	317 ↔ 331		PROSITE-ProRule annotation Manual assertion according to rulesⁱ PROSITE-ProRule:PRU00076
Disulfide bondⁱ	333 ↔ 346		PROSITE-ProRule annotation Manual assertion according to rulesⁱ PROSITE-ProRule:PRU00076
Disulfide bondⁱ	352 ↔ 363		PROSITE-ProRule annotation Manual assertion according to rulesⁱ PROSITE-ProRule:PRU00076
Disulfide bondⁱ	359 ↔ 373		PROSITE-ProRule annotation Manual assertion according to rulesⁱ PROSITE-ProRule:PRU00076
Disulfide bondⁱ	375 ↔ 388		PROSITE-ProRule annotation Manual assertion according to rulesⁱ PROSITE-ProRule:PRU00076
Disulfide bondⁱ	394 ↔ 405		PROSITE-ProRule annotation Manual assertion according to rulesⁱ PROSITE-ProRule:PRU00076
Disulfide bondⁱ	401 ↔ 415		PROSITE-ProRule annotation Manual assertion according to rulesⁱ PROSITE-ProRule:PRU00076
Disulfide bondⁱ	417 ↔ 430		PROSITE-ProRule annotation Manual assertion according to rulesⁱ PROSITE-ProRule:PRU00076
Modified residueⁱ	441 – 441	1	Phosphoserine; by FAM20C1 Publication Manual assertion based on experiment inⁱ Ref.9 "A single kinase generates the majority of the secreted phosphoproteome." Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J., Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N., Pinna L.A., Pagliarini D.J., Dixon J.E. Cell 161:1619-1632(2015) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-441 AND THR-442.
Modified residueⁱ	442 – 442	1	Phosphothreonine; by FAM20C1 Publication Manual assertion based on experiment inⁱ Ref.9 "A single kinase generates the majority of the secreted phosphoproteome." Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J., Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N., Pinna L.A., Pagliarini D.J., Dixon J.E. Cell 161:1619-1632(2015) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-441 AND THR-442.

Keywords - PTMⁱ

Disulfide bond, Phosphoprotein

Proteomic databases

MaxQBⁱ	O15232.
PaxDbⁱ	O15232.
PeptideAtlasⁱ	O15232.
PRIDEⁱ	O15232.

PTM databases

iPTMnetⁱ	O15232.
PhosphoSiteⁱ	O15232.

Miscellaneous databases

PMAP-CutDB	O15232.

PMAP-CutDB

O15232.

Expressionⁱ

Tissue specificityⁱ

Expressed only in cartilaginous tissues, such as vertebrae, ribs and shoulders.

Gene expression databases

Bgeeⁱ	ENSG00000132031.
CleanExⁱ	HS_MATN3.
Genevisibleⁱ	O15232. HS.

Interactionⁱ

Subunit structureⁱ

Can form homooligomers (monomers, dimers, trimers and tetramers) and heterooligomers with matrilin-1 (By similarity). Interacts with COMP.By similarity1 Publication

Binary interactionsⁱ

With	Entry	#Exp.	IntAct
KRTAP10-8	P60410	3	EBI-6262458,EBI-10171774
NOTCH2NL	Q7Z3S9	3	EBI-6262458,EBI-945833
TCF4	P15884	3	EBI-6262458,EBI-533224

With

Entry

#Exp.

IntAct

Notes

KRTAP10-8

P60410

3

EBI-6262458,EBI-10171774

NOTCH2NL

Q7Z3S9

3

EBI-6262458,EBI-945833

TCF4

P15884

3

EBI-6262458,EBI-533224

Protein-protein interaction databases

BioGridⁱ	110318. 7 interactions.
IntActⁱ	O15232. 4 interactions.
STRINGⁱ	9606.ENSP00000383894.

Structureⁱ

3D structure databases

ProteinModelPortalⁱ	O15232.
SMRⁱ	O15232. Positions 82-245, 255-432.
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	Length	Description	Actions
Domainⁱ	83 – 258	176	VWFAPROSITE-ProRule annotation Manual assertion according to rulesⁱ PROSITE-ProRule:PRU00219	Add BLAST
Domainⁱ	264 – 305	42	EGF-like 1PROSITE-ProRule annotation Manual assertion according to rulesⁱ PROSITE-ProRule:PRU00076	Add BLAST
Domainⁱ	306 – 347	42	EGF-like 2PROSITE-ProRule annotation Manual assertion according to rulesⁱ PROSITE-ProRule:PRU00076	Add BLAST
Domainⁱ	348 – 389	42	EGF-like 3PROSITE-ProRule annotation Manual assertion according to rulesⁱ PROSITE-ProRule:PRU00076	Add BLAST
Domainⁱ	390 – 431	42	EGF-like 4PROSITE-ProRule annotation Manual assertion according to rulesⁱ PROSITE-ProRule:PRU00076	Add BLAST

Coiled coil

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
Coiled coilⁱ	456 – 480	25	By similarity			Add BLAST

Sequence similaritiesⁱ

Contains 4 EGF-like domains.PROSITE-ProRule annotation

Contains 1 VWFA domain.PROSITE-ProRule annotation

Keywords - Domainⁱ

Coiled coil, EGF-like domain, Repeat, Signal

Phylogenomic databases

eggNOGⁱ	KOG1217. Eukaryota. ENOG4111IJ5. LUCA.
GeneTreeⁱ	ENSGT00760000119000.
HOGENOMⁱ	HOG000263415.
HOVERGENⁱ	HBG056906.
InParanoidⁱ	O15232.
KOⁱ	K19467.
OMAⁱ	RFQETFC.
OrthoDBⁱ	EOG091G04O4.
PhylomeDBⁱ	O15232.
TreeFamⁱ	TF330078.

Family and domain databases

Gene3Dⁱ	1.20.5.30. 1 hit. 3.40.50.410. 1 hit.
InterProⁱ	IPR001881. EGF-like_Ca-bd_dom. IPR013032. EGF-like_CS. IPR000742. EGF-like_dom. IPR009030. Growth_fac_rcpt_. IPR030765. Matrilin-3/4. IPR019466. Matrilin_coiled-coil_trimer. IPR002035. VWF_A. [Graphical view]
PANTHERⁱ	PTHR11132:SF50. PTHR11132:SF50. 1 hit.
Pfamⁱ	PF07645. EGF_CA. 1 hit. PF10393. Matrilin_ccoil. 1 hit. PF00092. VWA. 1 hit. [Graphical view]
SMARTⁱ	SM00181. EGF. 4 hits. SM00179. EGF_CA. 4 hits. SM01279. Matrilin_ccoil. 1 hit. SM00327. VWA. 1 hit. [Graphical view]
SUPFAMⁱ	SSF53300. SSF53300. 1 hit. SSF57184. SSF57184. 1 hit.
PROSITEⁱ	PS01186. EGF_2. 4 hits. PS50026. EGF_3. 4 hits. PS50234. VWFA. 1 hit. [Graphical view]

Sequences (2)ⁱ

Sequence statusⁱ: Complete.

Sequence processingⁱ: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsⁱ produced by alternative splicing. Align Add to basket Added to basket

Isoform 1 (identifier: O15232-1) [UniParc]FASTA Add to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MPRPAPARRL PGLLLLLWPL LLLPSAAPDP VARPGFRRLE TRGPGGSPGR 
        60         70         80         90        100
RPSPAAPDGA PASGTSEPGR ARGAGVCKSR PLDLVFIIDS SRSVRPLEFT 
       110        120        130        140        150
KVKTFVSRII DTLDIGPADT RVAVVNYAST VKIEFQLQAY TDKQSLKQAV 
       160        170        180        190        200
GRITPLSTGT MSGLAIQTAM DEAFTVEAGA REPSSNIPKV AIIVTDGRPQ 
       210        220        230        240        250
DQVNEVAARA QASGIELYAV GVDRADMASL KMMASEPLEE HVFYVETYGV 
       260        270        280        290        300
IEKLSSRFQE TFCALDPCVL GTHQCQHVCI SDGEGKHHCE CSQGYTLNAD 
       310        320        330        340        350
KKTCSALDRC ALNTHGCEHI CVNDRSGSYH CECYEGYTLN EDRKTCSAQD 
       360        370        380        390        400
KCALGTHGCQ HICVNDRTGS HHCECYEGYT LNADKKTCSV RDKCALGSHG 
       410        420        430        440        450
CQHICVSDGA ASYHCDCYPG YTLNEDKKTC SATEEARRLV STEDACGCEA 
       460        470        480 
TLAFQDKVSS YLQRLNTKLD DILEKLKINE YGQIHR

Length:486

Mass (Da):52,817

Last modified:May 1, 1999 - v2

Checksum:ⁱ688847BCC791B331

GO

Isoform 2 (identifier: O15232-2) [UniParc]FASTA Add to basket

The sequence of this isoform differs from the canonical sequence as follows:
266-307: Missing.

« Hide

        10         20         30         40         50
MPRPAPARRL PGLLLLLWPL LLLPSAAPDP VARPGFRRLE TRGPGGSPGR 
        60         70         80         90        100
RPSPAAPDGA PASGTSEPGR ARGAGVCKSR PLDLVFIIDS SRSVRPLEFT 
       110        120        130        140        150
KVKTFVSRII DTLDIGPADT RVAVVNYAST VKIEFQLQAY TDKQSLKQAV 
       160        170        180        190        200
GRITPLSTGT MSGLAIQTAM DEAFTVEAGA REPSSNIPKV AIIVTDGRPQ 
       210        220        230        240        250
DQVNEVAARA QASGIELYAV GVDRADMASL KMMASEPLEE HVFYVETYGV 
       260        270        280        290        300
IEKLSSRFQE TFCALDRCAL NTHGCEHICV NDRSGSYHCE CYEGYTLNED 
       310        320        330        340        350
RKTCSAQDKC ALGTHGCQHI CVNDRTGSHH CECYEGYTLN ADKKTCSVRD 
       360        370        380        390        400
KCALGSHGCQ HICVSDGAAS YHCDCYPGYT LNEDKKTCSA TEEARRLVST 
       410        420        430        440 
EDACGCEATL AFQDKVSSYL QRLNTKLDDI LEKLKINEYG QIHR

Show »

Length:444

Mass (Da):48,317

Checksum:ⁱ86E2198CA1627B15

GO

Natural variant

Feature key	Position(s)	Length	Description	Feature identifier
Natural variantⁱ	11 – 11	1	P → S.1 Publication Manual assertion based on experiment inⁱ Ref.13 "Novel and recurrent mutations clustered in the von Willebrand factor A domain of MATN3 in multiple epiphyseal dysplasia." Mabuchi A., Haga N., Maeda K., Nakashima E., Manabe N., Hiraoka H., Kitoh H., Kosaki R., Nishimura G., Ohashi H., Ikegawa S. Hum. Mutat. 24:439-440(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 SER-105; MET-120 AND TRP-121, VARIANTS SER-11; LYS-252 AND MET-303.	VAR_019881
Natural variantⁱ	70 – 70	1	R → H in EDM5. 1 Publication Manual assertion based on experiment inⁱ Ref.16 "Mutation in the von Willebrand factor-A domain is not a prerequisite for the MATN3 mutation in multiple epiphyseal dysplasia." Maeda K., Nakashima E., Horikoshi T., Mabuchi A., Ikegawa S. Am. J. Med. Genet. A 136:285-286(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT EDM5 HIS-70. Corresponds to variant rs104893640 [ dbSNP \| Ensembl ].	VAR_054807
Natural variantⁱ	105 – 105	1	F → S in EDM5. 1 Publication Manual assertion based on experiment inⁱ Ref.13 "Novel and recurrent mutations clustered in the von Willebrand factor A domain of MATN3 in multiple epiphyseal dysplasia." Mabuchi A., Haga N., Maeda K., Nakashima E., Manabe N., Hiraoka H., Kitoh H., Kosaki R., Nishimura G., Ohashi H., Ikegawa S. Hum. Mutat. 24:439-440(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 SER-105; MET-120 AND TRP-121, VARIANTS SER-11; LYS-252 AND MET-303.	VAR_020844
Natural variantⁱ	120 – 120	1	T → M in EDM5; retained and accumulates within the cell. 4 Publications Manual assertion based on experiment inⁱ Ref.13 "Novel and recurrent mutations clustered in the von Willebrand factor A domain of MATN3 in multiple epiphyseal dysplasia." Mabuchi A., Haga N., Maeda K., Nakashima E., Manabe N., Hiraoka H., Kitoh H., Kosaki R., Nishimura G., Ohashi H., Ikegawa S. Hum. Mutat. 24:439-440(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 SER-105; MET-120 AND TRP-121, VARIANTS SER-11; LYS-252 AND MET-303. Ref.14 "Missense mutations in the beta strands of the single A-domain of matrilin-3 result in multiple epiphyseal dysplasia." Jackson G.C., Barker F.S., Jakkula E., Czarny-Ratajczak M., Maekitie O., Cole W.G., Wright M.J., Smithson S.F., Suri M., Rogala P., Mortier G.R., Baldock C., Wallace A., Elles R., Ala-Kokko L., Briggs M.D. J. Med. Genet. 41:52-59(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 MET-120; TRP-121; LYS-134; ASN-192 AND ASP-219, VARIANTS LYS-252 AND MET-303. Ref.17 "Multiple epiphyseal dysplasia mutations in MATN3 cause misfolding of the A-domain and prevent secretion of mutant matrilin-3." Cotterill S.L., Jackson G.C., Leighton M.P., Wagener R., Maekitie O., Cole W.G., Briggs M.D. Hum. Mutat. 26:557-565(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 TRP-121; LYS-195 AND ASN-218, VARIANT LYS-252, CHARACTERIZATION OF VARIANTS MET-120; TRP-121; LYS-134; ASN-192; ASP-194 AND ASP-219, CHARACTERIZATION OF VARIANT LYS-252. Ref.18 "Pseudoachondroplasia and multiple epiphyseal dysplasia: A 7-year comprehensive analysis of the known disease genes identify novel and recurrent mutations and provides an accurate assessment of their relative contribution." Jackson G.C., Mittaz-Crettol L., Taylor J.A., Mortier G.R., Spranger J., Zabel B., Le Merrer M., Cormier-Daire V., Hall C.M., Offiah A., Wright M.J., Savarirayan R., Nishimura G., Ramsden S.C., Elles R., Bonafe L., Superti-Furga A., Unger S., Zankl A., Briggs M.D. Hum. Mutat. 33:144-157(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 MET-120; TRP-121; 171-ASP--VAL-176 DEL; ASP-173; LYS-195; PRO-209; ASN-218; ASP-219; ASN-231 AND MET-245. Corresponds to variant rs397515546 [ dbSNP \| Ensembl ].	VAR_019882
Natural variantⁱ	121 – 121	1	R → W in EDM5; retained and accumulates within the cell. 5 Publications Manual assertion based on experiment inⁱ Ref.10 "Mutations in the region encoding the von Willebrand factor A domain of matrilin-3 are associated with multiple epiphyseal dysplasia." Chapman K.L., Mortier G.R., Chapman K., Loughlin J., Grant M.E., Briggs M.D. Nat. Genet. 28:393-396(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 TRP-121 AND ASP-194. Ref.13 "Novel and recurrent mutations clustered in the von Willebrand factor A domain of MATN3 in multiple epiphyseal dysplasia." Mabuchi A., Haga N., Maeda K., Nakashima E., Manabe N., Hiraoka H., Kitoh H., Kosaki R., Nishimura G., Ohashi H., Ikegawa S. Hum. Mutat. 24:439-440(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 SER-105; MET-120 AND TRP-121, VARIANTS SER-11; LYS-252 AND MET-303. Ref.14 "Missense mutations in the beta strands of the single A-domain of matrilin-3 result in multiple epiphyseal dysplasia." Jackson G.C., Barker F.S., Jakkula E., Czarny-Ratajczak M., Maekitie O., Cole W.G., Wright M.J., Smithson S.F., Suri M., Rogala P., Mortier G.R., Baldock C., Wallace A., Elles R., Ala-Kokko L., Briggs M.D. J. Med. Genet. 41:52-59(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 MET-120; TRP-121; LYS-134; ASN-192 AND ASP-219, VARIANTS LYS-252 AND MET-303. Ref.17 "Multiple epiphyseal dysplasia mutations in MATN3 cause misfolding of the A-domain and prevent secretion of mutant matrilin-3." Cotterill S.L., Jackson G.C., Leighton M.P., Wagener R., Maekitie O., Cole W.G., Briggs M.D. Hum. Mutat. 26:557-565(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 TRP-121; LYS-195 AND ASN-218, VARIANT LYS-252, CHARACTERIZATION OF VARIANTS MET-120; TRP-121; LYS-134; ASN-192; ASP-194 AND ASP-219, CHARACTERIZATION OF VARIANT LYS-252. Ref.18 "Pseudoachondroplasia and multiple epiphyseal dysplasia: A 7-year comprehensive analysis of the known disease genes identify novel and recurrent mutations and provides an accurate assessment of their relative contribution." Jackson G.C., Mittaz-Crettol L., Taylor J.A., Mortier G.R., Spranger J., Zabel B., Le Merrer M., Cormier-Daire V., Hall C.M., Offiah A., Wright M.J., Savarirayan R., Nishimura G., Ramsden S.C., Elles R., Bonafe L., Superti-Furga A., Unger S., Zankl A., Briggs M.D. Hum. Mutat. 33:144-157(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 MET-120; TRP-121; 171-ASP--VAL-176 DEL; ASP-173; LYS-195; PRO-209; ASN-218; ASP-219; ASN-231 AND MET-245. Corresponds to variant rs104893637 [ dbSNP \| Ensembl ].	VAR_013691
Natural variantⁱ	128 – 128	1	A → P in EDM5; bilateral hereditary microepiphyseal dysplasia. 1 Publication Manual assertion based on experiment inⁱ Ref.12 "Familial multiple epiphyseal dysplasia due to a matrilin-3 mutation: further delineation of the phenotype including 40 years follow-up." Mostert A.K., Dijkstra P.F., Jansen B.R.H., van Horn J.R., de Graaf B., Heutink P., Lindhout D. Am. J. Med. Genet. A 120:490-497(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT EDM5 PRO-128. Corresponds to variant rs104893641 [ dbSNP \| Ensembl ].	VAR_019883
Natural variantⁱ	134 – 134	1	E → K in EDM5; retained and accumulates within the cell. 2 Publications Manual assertion based on experiment inⁱ Ref.14 "Missense mutations in the beta strands of the single A-domain of matrilin-3 result in multiple epiphyseal dysplasia." Jackson G.C., Barker F.S., Jakkula E., Czarny-Ratajczak M., Maekitie O., Cole W.G., Wright M.J., Smithson S.F., Suri M., Rogala P., Mortier G.R., Baldock C., Wallace A., Elles R., Ala-Kokko L., Briggs M.D. J. Med. Genet. 41:52-59(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 MET-120; TRP-121; LYS-134; ASN-192 AND ASP-219, VARIANTS LYS-252 AND MET-303. Ref.17 "Multiple epiphyseal dysplasia mutations in MATN3 cause misfolding of the A-domain and prevent secretion of mutant matrilin-3." Cotterill S.L., Jackson G.C., Leighton M.P., Wagener R., Maekitie O., Cole W.G., Briggs M.D. Hum. Mutat. 26:557-565(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 TRP-121; LYS-195 AND ASN-218, VARIANT LYS-252, CHARACTERIZATION OF VARIANTS MET-120; TRP-121; LYS-134; ASN-192; ASP-194 AND ASP-219, CHARACTERIZATION OF VARIANT LYS-252.	VAR_019884
Natural variantⁱ	171 – 176	6	Missing in EDM5. 1 Publication Manual assertion based on experiment inⁱ Ref.18 "Pseudoachondroplasia and multiple epiphyseal dysplasia: A 7-year comprehensive analysis of the known disease genes identify novel and recurrent mutations and provides an accurate assessment of their relative contribution." Jackson G.C., Mittaz-Crettol L., Taylor J.A., Mortier G.R., Spranger J., Zabel B., Le Merrer M., Cormier-Daire V., Hall C.M., Offiah A., Wright M.J., Savarirayan R., Nishimura G., Ramsden S.C., Elles R., Bonafe L., Superti-Furga A., Unger S., Zankl A., Briggs M.D. Hum. Mutat. 33:144-157(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 MET-120; TRP-121; 171-ASP--VAL-176 DEL; ASP-173; LYS-195; PRO-209; ASN-218; ASP-219; ASN-231 AND MET-245.	VAR_066830
Natural variantⁱ	173 – 173	1	A → D in EDM5. 1 Publication Manual assertion based on experiment inⁱ Ref.18 "Pseudoachondroplasia and multiple epiphyseal dysplasia: A 7-year comprehensive analysis of the known disease genes identify novel and recurrent mutations and provides an accurate assessment of their relative contribution." Jackson G.C., Mittaz-Crettol L., Taylor J.A., Mortier G.R., Spranger J., Zabel B., Le Merrer M., Cormier-Daire V., Hall C.M., Offiah A., Wright M.J., Savarirayan R., Nishimura G., Ramsden S.C., Elles R., Bonafe L., Superti-Furga A., Unger S., Zankl A., Briggs M.D. Hum. Mutat. 33:144-157(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 MET-120; TRP-121; 171-ASP--VAL-176 DEL; ASP-173; LYS-195; PRO-209; ASN-218; ASP-219; ASN-231 AND MET-245.	VAR_066831
Natural variantⁱ	192 – 192	1	I → N in EDM5; retained and accumulates within the cell. 2 Publications Manual assertion based on experiment inⁱ Ref.14 "Missense mutations in the beta strands of the single A-domain of matrilin-3 result in multiple epiphyseal dysplasia." Jackson G.C., Barker F.S., Jakkula E., Czarny-Ratajczak M., Maekitie O., Cole W.G., Wright M.J., Smithson S.F., Suri M., Rogala P., Mortier G.R., Baldock C., Wallace A., Elles R., Ala-Kokko L., Briggs M.D. J. Med. Genet. 41:52-59(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 MET-120; TRP-121; LYS-134; ASN-192 AND ASP-219, VARIANTS LYS-252 AND MET-303. Ref.17 "Multiple epiphyseal dysplasia mutations in MATN3 cause misfolding of the A-domain and prevent secretion of mutant matrilin-3." Cotterill S.L., Jackson G.C., Leighton M.P., Wagener R., Maekitie O., Cole W.G., Briggs M.D. Hum. Mutat. 26:557-565(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 TRP-121; LYS-195 AND ASN-218, VARIANT LYS-252, CHARACTERIZATION OF VARIANTS MET-120; TRP-121; LYS-134; ASN-192; ASP-194 AND ASP-219, CHARACTERIZATION OF VARIANT LYS-252.	VAR_019885
Natural variantⁱ	194 – 194	1	V → D in EDM5; retained and accumulates within the cell. 2 Publications Manual assertion based on experiment inⁱ Ref.10 "Mutations in the region encoding the von Willebrand factor A domain of matrilin-3 are associated with multiple epiphyseal dysplasia." Chapman K.L., Mortier G.R., Chapman K., Loughlin J., Grant M.E., Briggs M.D. Nat. Genet. 28:393-396(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 TRP-121 AND ASP-194. Ref.17 "Multiple epiphyseal dysplasia mutations in MATN3 cause misfolding of the A-domain and prevent secretion of mutant matrilin-3." Cotterill S.L., Jackson G.C., Leighton M.P., Wagener R., Maekitie O., Cole W.G., Briggs M.D. Hum. Mutat. 26:557-565(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 TRP-121; LYS-195 AND ASN-218, VARIANT LYS-252, CHARACTERIZATION OF VARIANTS MET-120; TRP-121; LYS-134; ASN-192; ASP-194 AND ASP-219, CHARACTERIZATION OF VARIANT LYS-252. Corresponds to variant rs104893645 [ dbSNP \| Ensembl ].	VAR_013692
Natural variantⁱ	195 – 195	1	T → K in EDM5. 2 Publications Manual assertion based on experiment inⁱ Ref.17 "Multiple epiphyseal dysplasia mutations in MATN3 cause misfolding of the A-domain and prevent secretion of mutant matrilin-3." Cotterill S.L., Jackson G.C., Leighton M.P., Wagener R., Maekitie O., Cole W.G., Briggs M.D. Hum. Mutat. 26:557-565(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 TRP-121; LYS-195 AND ASN-218, VARIANT LYS-252, CHARACTERIZATION OF VARIANTS MET-120; TRP-121; LYS-134; ASN-192; ASP-194 AND ASP-219, CHARACTERIZATION OF VARIANT LYS-252. Ref.18 "Pseudoachondroplasia and multiple epiphyseal dysplasia: A 7-year comprehensive analysis of the known disease genes identify novel and recurrent mutations and provides an accurate assessment of their relative contribution." Jackson G.C., Mittaz-Crettol L., Taylor J.A., Mortier G.R., Spranger J., Zabel B., Le Merrer M., Cormier-Daire V., Hall C.M., Offiah A., Wright M.J., Savarirayan R., Nishimura G., Ramsden S.C., Elles R., Bonafe L., Superti-Furga A., Unger S., Zankl A., Briggs M.D. Hum. Mutat. 33:144-157(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 MET-120; TRP-121; 171-ASP--VAL-176 DEL; ASP-173; LYS-195; PRO-209; ASN-218; ASP-219; ASN-231 AND MET-245.	VAR_054808
Natural variantⁱ	209 – 209	1	R → P in EDM5. 1 Publication Manual assertion based on experiment inⁱ Ref.18 "Pseudoachondroplasia and multiple epiphyseal dysplasia: A 7-year comprehensive analysis of the known disease genes identify novel and recurrent mutations and provides an accurate assessment of their relative contribution." Jackson G.C., Mittaz-Crettol L., Taylor J.A., Mortier G.R., Spranger J., Zabel B., Le Merrer M., Cormier-Daire V., Hall C.M., Offiah A., Wright M.J., Savarirayan R., Nishimura G., Ramsden S.C., Elles R., Bonafe L., Superti-Furga A., Unger S., Zankl A., Briggs M.D. Hum. Mutat. 33:144-157(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 MET-120; TRP-121; 171-ASP--VAL-176 DEL; ASP-173; LYS-195; PRO-209; ASN-218; ASP-219; ASN-231 AND MET-245. Corresponds to variant rs749845872 [ dbSNP \| Ensembl ].	VAR_066832
Natural variantⁱ	218 – 218	1	Y → N in EDM5. 2 Publications Manual assertion based on experiment inⁱ Ref.17 "Multiple epiphyseal dysplasia mutations in MATN3 cause misfolding of the A-domain and prevent secretion of mutant matrilin-3." Cotterill S.L., Jackson G.C., Leighton M.P., Wagener R., Maekitie O., Cole W.G., Briggs M.D. Hum. Mutat. 26:557-565(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 TRP-121; LYS-195 AND ASN-218, VARIANT LYS-252, CHARACTERIZATION OF VARIANTS MET-120; TRP-121; LYS-134; ASN-192; ASP-194 AND ASP-219, CHARACTERIZATION OF VARIANT LYS-252. Ref.18 "Pseudoachondroplasia and multiple epiphyseal dysplasia: A 7-year comprehensive analysis of the known disease genes identify novel and recurrent mutations and provides an accurate assessment of their relative contribution." Jackson G.C., Mittaz-Crettol L., Taylor J.A., Mortier G.R., Spranger J., Zabel B., Le Merrer M., Cormier-Daire V., Hall C.M., Offiah A., Wright M.J., Savarirayan R., Nishimura G., Ramsden S.C., Elles R., Bonafe L., Superti-Furga A., Unger S., Zankl A., Briggs M.D. Hum. Mutat. 33:144-157(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 MET-120; TRP-121; 171-ASP--VAL-176 DEL; ASP-173; LYS-195; PRO-209; ASN-218; ASP-219; ASN-231 AND MET-245.	VAR_054809
Natural variantⁱ	219 – 219	1	A → D in EDM5; retained and accumulates within the cell. 3 Publications Manual assertion based on experiment inⁱ Ref.14 "Missense mutations in the beta strands of the single A-domain of matrilin-3 result in multiple epiphyseal dysplasia." Jackson G.C., Barker F.S., Jakkula E., Czarny-Ratajczak M., Maekitie O., Cole W.G., Wright M.J., Smithson S.F., Suri M., Rogala P., Mortier G.R., Baldock C., Wallace A., Elles R., Ala-Kokko L., Briggs M.D. J. Med. Genet. 41:52-59(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 MET-120; TRP-121; LYS-134; ASN-192 AND ASP-219, VARIANTS LYS-252 AND MET-303. Ref.17 "Multiple epiphyseal dysplasia mutations in MATN3 cause misfolding of the A-domain and prevent secretion of mutant matrilin-3." Cotterill S.L., Jackson G.C., Leighton M.P., Wagener R., Maekitie O., Cole W.G., Briggs M.D. Hum. Mutat. 26:557-565(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 TRP-121; LYS-195 AND ASN-218, VARIANT LYS-252, CHARACTERIZATION OF VARIANTS MET-120; TRP-121; LYS-134; ASN-192; ASP-194 AND ASP-219, CHARACTERIZATION OF VARIANT LYS-252. Ref.18 "Pseudoachondroplasia and multiple epiphyseal dysplasia: A 7-year comprehensive analysis of the known disease genes identify novel and recurrent mutations and provides an accurate assessment of their relative contribution." Jackson G.C., Mittaz-Crettol L., Taylor J.A., Mortier G.R., Spranger J., Zabel B., Le Merrer M., Cormier-Daire V., Hall C.M., Offiah A., Wright M.J., Savarirayan R., Nishimura G., Ramsden S.C., Elles R., Bonafe L., Superti-Furga A., Unger S., Zankl A., Briggs M.D. Hum. Mutat. 33:144-157(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 MET-120; TRP-121; 171-ASP--VAL-176 DEL; ASP-173; LYS-195; PRO-209; ASN-218; ASP-219; ASN-231 AND MET-245. Corresponds to variant rs28939677 [ dbSNP \| Ensembl ].	VAR_019886
Natural variantⁱ	231 – 231	1	K → N in EDM5. 1 Publication Manual assertion based on experiment inⁱ Ref.18 "Pseudoachondroplasia and multiple epiphyseal dysplasia: A 7-year comprehensive analysis of the known disease genes identify novel and recurrent mutations and provides an accurate assessment of their relative contribution." Jackson G.C., Mittaz-Crettol L., Taylor J.A., Mortier G.R., Spranger J., Zabel B., Le Merrer M., Cormier-Daire V., Hall C.M., Offiah A., Wright M.J., Savarirayan R., Nishimura G., Ramsden S.C., Elles R., Bonafe L., Superti-Furga A., Unger S., Zankl A., Briggs M.D. Hum. Mutat. 33:144-157(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 MET-120; TRP-121; 171-ASP--VAL-176 DEL; ASP-173; LYS-195; PRO-209; ASN-218; ASP-219; ASN-231 AND MET-245. Corresponds to variant rs773642745 [ dbSNP \| Ensembl ].	VAR_066833
Natural variantⁱ	245 – 245	1	V → M in EDM5. 1 Publication Manual assertion based on experiment inⁱ Ref.18 "Pseudoachondroplasia and multiple epiphyseal dysplasia: A 7-year comprehensive analysis of the known disease genes identify novel and recurrent mutations and provides an accurate assessment of their relative contribution." Jackson G.C., Mittaz-Crettol L., Taylor J.A., Mortier G.R., Spranger J., Zabel B., Le Merrer M., Cormier-Daire V., Hall C.M., Offiah A., Wright M.J., Savarirayan R., Nishimura G., Ramsden S.C., Elles R., Bonafe L., Superti-Furga A., Unger S., Zankl A., Briggs M.D. Hum. Mutat. 33:144-157(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 MET-120; TRP-121; 171-ASP--VAL-176 DEL; ASP-173; LYS-195; PRO-209; ASN-218; ASP-219; ASN-231 AND MET-245. Corresponds to variant rs182164052 [ dbSNP \| Ensembl ].	VAR_066834
Natural variantⁱ	252 – 252	1	E → K Secreted normally as the wild-type. 3 Publications Manual assertion based on experiment inⁱ Ref.13 "Novel and recurrent mutations clustered in the von Willebrand factor A domain of MATN3 in multiple epiphyseal dysplasia." Mabuchi A., Haga N., Maeda K., Nakashima E., Manabe N., Hiraoka H., Kitoh H., Kosaki R., Nishimura G., Ohashi H., Ikegawa S. Hum. Mutat. 24:439-440(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 SER-105; MET-120 AND TRP-121, VARIANTS SER-11; LYS-252 AND MET-303. Ref.14 "Missense mutations in the beta strands of the single A-domain of matrilin-3 result in multiple epiphyseal dysplasia." Jackson G.C., Barker F.S., Jakkula E., Czarny-Ratajczak M., Maekitie O., Cole W.G., Wright M.J., Smithson S.F., Suri M., Rogala P., Mortier G.R., Baldock C., Wallace A., Elles R., Ala-Kokko L., Briggs M.D. J. Med. Genet. 41:52-59(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 MET-120; TRP-121; LYS-134; ASN-192 AND ASP-219, VARIANTS LYS-252 AND MET-303. Ref.17 "Multiple epiphyseal dysplasia mutations in MATN3 cause misfolding of the A-domain and prevent secretion of mutant matrilin-3." Cotterill S.L., Jackson G.C., Leighton M.P., Wagener R., Maekitie O., Cole W.G., Briggs M.D. Hum. Mutat. 26:557-565(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 TRP-121; LYS-195 AND ASN-218, VARIANT LYS-252, CHARACTERIZATION OF VARIANTS MET-120; TRP-121; LYS-134; ASN-192; ASP-194 AND ASP-219, CHARACTERIZATION OF VARIANT LYS-252. Corresponds to variant rs52826764 [ dbSNP \| Ensembl ].	VAR_019887
Natural variantⁱ	303 – 303	1	T → M.3 Publications Manual assertion based on experiment inⁱ Ref.11 "Genomewide scan for hand osteoarthritis: a novel mutation in matrilin-3." Stefansson S.E., Jonsson H., Ingvarsson T., Manolescu I., Jonsson H.H., Olafsdottir G., Palsdottir E., Stefansdottir G., Sveinbjornsdottir G., Frigge M.L., Kong A., Gulcher J.R., Stefansson K. Am. J. Hum. Genet. 72:1448-1459(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MET-303, INVOLVEMENT IN OS2. Ref.13 "Novel and recurrent mutations clustered in the von Willebrand factor A domain of MATN3 in multiple epiphyseal dysplasia." Mabuchi A., Haga N., Maeda K., Nakashima E., Manabe N., Hiraoka H., Kitoh H., Kosaki R., Nishimura G., Ohashi H., Ikegawa S. Hum. Mutat. 24:439-440(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 SER-105; MET-120 AND TRP-121, VARIANTS SER-11; LYS-252 AND MET-303. Ref.14 "Missense mutations in the beta strands of the single A-domain of matrilin-3 result in multiple epiphyseal dysplasia." Jackson G.C., Barker F.S., Jakkula E., Czarny-Ratajczak M., Maekitie O., Cole W.G., Wright M.J., Smithson S.F., Suri M., Rogala P., Mortier G.R., Baldock C., Wallace A., Elles R., Ala-Kokko L., Briggs M.D. J. Med. Genet. 41:52-59(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EDM5 MET-120; TRP-121; LYS-134; ASN-192 AND ASP-219, VARIANTS LYS-252 AND MET-303. Corresponds to variant rs28939676 [ dbSNP \| Ensembl ].	VAR_015852
Natural variantⁱ	304 – 304	1	C → S in SEMD-MATN3. 1 Publication Manual assertion based on experiment inⁱ Ref.15 "Spondylo-epi-metaphyseal dysplasia (SEMD) matrilin 3 type: homozygote matrilin 3 mutation in a novel form of SEMD." Borochowitz Z.U., Scheffer D., Adir V., Dagoneau N., Munnich A., Cormier-Daire V. J. Med. Genet. 41:366-372(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT SEMD-MATN3 SER-304. Corresponds to variant rs104893639 [ dbSNP \| Ensembl ].	VAR_019888

Alternative sequence

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
Alternative sequenceⁱ	266 – 307	42	Missing in isoform 2. 1 Publication Manual assertion based on opinion inⁱ Ref.2 "Matrilin-3 increases not only upon osteoarthritis but also in cartilage-forming tumors and down-regulates SOX9 via EGF domain 1-dependent signaling." Vincourt J.-B., Takigawa M. Submitted (MAR-2008) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).		VSP_054374	Add BLAST

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	AJ224741 mRNA. Translation: CAA12110.1. EU541440 mRNA. Translation: ACB29772.1. AC079145 Genomic DNA. Translation: AAX88937.1. CH471053 Genomic DNA. Translation: EAX00837.1. BC139907 mRNA. Translation: AAI39908.1. AJ001047 mRNA. Translation: CAA04501.1. Y13341 mRNA. Translation: CAA73785.1.
CCDSⁱ	CCDS46226.1. [O15232-1]
RefSeqⁱ	NP_002372.1. NM_002381.4. [O15232-1]
UniGeneⁱ	Hs.656199.

Genome annotation databases

Ensemblⁱ	ENST00000407540; ENSP00000383894; ENSG00000132031. [O15232-1] ENST00000421259; ENSP00000398753; ENSG00000132031. [O15232-2]
GeneIDⁱ	4148.
KEGGⁱ	hsa:4148.
UCSCⁱ	uc002rdl.4. human. [O15232-1]

Keywords - Coding sequence diversityⁱ

Alternative splicing, Polymorphism

Cross-referencesⁱ

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	AJ224741 mRNA. Translation: CAA12110.1. EU541440 mRNA. Translation: ACB29772.1. AC079145 Genomic DNA. Translation: AAX88937.1. CH471053 Genomic DNA. Translation: EAX00837.1. BC139907 mRNA. Translation: AAI39908.1. AJ001047 mRNA. Translation: CAA04501.1. Y13341 mRNA. Translation: CAA73785.1.
CCDSⁱ	CCDS46226.1. [O15232-1]
RefSeqⁱ	NP_002372.1. NM_002381.4. [O15232-1]
UniGeneⁱ	Hs.656199.

3D structure databases

ProteinModelPortalⁱ	O15232.
SMRⁱ	O15232. Positions 82-245, 255-432.
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	110318. 7 interactions.
IntActⁱ	O15232. 4 interactions.
STRINGⁱ	9606.ENSP00000383894.

PTM databases

iPTMnetⁱ	O15232.
PhosphoSiteⁱ	O15232.

Polymorphism and mutation databases

BioMutaⁱ	MATN3.

BioMutaⁱ

MATN3.

Proteomic databases

MaxQBⁱ	O15232.
PaxDbⁱ	O15232.
PeptideAtlasⁱ	O15232.
PRIDEⁱ	O15232.

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

Genome annotation databases

Ensemblⁱ	ENST00000407540; ENSP00000383894; ENSG00000132031. [O15232-1] ENST00000421259; ENSP00000398753; ENSG00000132031. [O15232-2]
GeneIDⁱ	4148.
KEGGⁱ	hsa:4148.
UCSCⁱ	uc002rdl.4. human. [O15232-1]

Organism-specific databases

CTDⁱ	4148.
GeneCardsⁱ	MATN3.
GeneReviewsⁱ	MATN3.
HGNCⁱ	HGNC:6909. MATN3.
MalaCardsⁱ	MATN3.
MIMⁱ	140600. phenotype. 602109. gene. 607078. phenotype. 608728. phenotype.
neXtProtⁱ	NX_O15232.
Orphanetⁱ	93311. Multiple epiphyseal dysplasia type 5. 156728. Spondyloepimetaphyseal dysplasia, matrilin-3 type.
PharmGKBⁱ	PA30652.
GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	KOG1217. Eukaryota. ENOG4111IJ5. LUCA.
GeneTreeⁱ	ENSGT00760000119000.
HOGENOMⁱ	HOG000263415.
HOVERGENⁱ	HBG056906.
InParanoidⁱ	O15232.
KOⁱ	K19467.
OMAⁱ	RFQETFC.
OrthoDBⁱ	EOG091G04O4.
PhylomeDBⁱ	O15232.
TreeFamⁱ	TF330078.

Enzyme and pathway databases

Reactomeⁱ	R-HSA-3000178. ECM proteoglycans.

Reactomeⁱ

R-HSA-3000178. ECM proteoglycans.

Miscellaneous databases

GeneWikiⁱ	MATN3.
GenomeRNAiⁱ	4148.
PMAP-CutDB	O15232.
PROⁱ	O15232.
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000132031.
CleanExⁱ	HS_MATN3.
Genevisibleⁱ	O15232. HS.

Family and domain databases

Gene3Dⁱ	1.20.5.30. 1 hit. 3.40.50.410. 1 hit.
InterProⁱ	IPR001881. EGF-like_Ca-bd_dom. IPR013032. EGF-like_CS. IPR000742. EGF-like_dom. IPR009030. Growth_fac_rcpt_. IPR030765. Matrilin-3/4. IPR019466. Matrilin_coiled-coil_trimer. IPR002035. VWF_A. [Graphical view]
PANTHERⁱ	PTHR11132:SF50. PTHR11132:SF50. 1 hit.
Pfamⁱ	PF07645. EGF_CA. 1 hit. PF10393. Matrilin_ccoil. 1 hit. PF00092. VWA. 1 hit. [Graphical view]
SMARTⁱ	SM00181. EGF. 4 hits. SM00179. EGF_CA. 4 hits. SM01279. Matrilin_ccoil. 1 hit. SM00327. VWA. 1 hit. [Graphical view]
SUPFAMⁱ	SSF53300. SSF53300. 1 hit. SSF57184. SSF57184. 1 hit.
PROSITEⁱ	PS01186. EGF_2. 4 hits. PS50026. EGF_3. 4 hits. PS50234. VWFA. 1 hit. [Graphical view]
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ

MATN3_HUMAN

Accessionⁱ

Primary (citable) accession number: O15232
Secondary accession number(s): B2CPU0, Q4ZG02

Entry historyⁱ

Integrated into UniProtKB/Swiss-Prot:	June 20, 2001
Last sequence update:	May 1, 1999
Last modified:	September 7, 2016
This is version 162 of the entry and version 2 of the sequence. [Complete history]

Entry statusⁱ

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousⁱ

Keywords - Technical termⁱ

Complete proteome, Reference proteome

Documents

Human chromosome 2
Human chromosome 2: entries, gene names and cross-references to MIM
Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations
Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations
MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
SIMILARITY comments
Index of protein domains and families

Similar proteinsⁱ

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:

100%	UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%	UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%	UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

UniProtKB

UniParc

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UniRef

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Supporting data

UniProtKB - O15232 (MATN3_HUMAN)

UniProt

O15232 - MATN3_HUMAN

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Matrilin-3

Select a section on the left to see content.

<p>Provides any useful information about the protein, mostly biological knowledge.</p><p><a href='../manual/function_section' target='_top'>More...</a></p>Functioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:</p><p><a href='../manual/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:</p><p><a href='../manual/gene_ontology' target='_top'>More...</a></p>GO - Biological processi

Enzyme and pathway databases

<p>Provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.</p><p><a href='../manual/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>Provides information on the location and the topology of the mature protein in the cell.</p><p><a href='../manual/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:</p><p><a href='../manual/gene_ontology' target='_top'>More...</a></p>GO - Cellular componenti

<p>Provides information on the disease(s) and phenotype(s) associated with a protein.</p><p><a href='../manual/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Organism-specific databases

Polymorphism and mutation databases

<p>Describes post-translational modifications (PTMs) and/or processing events.</p><p><a href='../manual/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Proteomic databases

PTM databases

Miscellaneous databases

<p>Provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.</p><p><a href='../manual/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

<p>Provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.</p><p><a href='../manual/interaction_section' target='_top'>More...</a></p>Interactioni

Protein-protein interaction databases

<p>Provides information on the tertiary and secondary structure of a protein.</p><p><a href='../manual/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

<p>Provides information on sequence similarities with other proteins and the domain(s) present in a protein.</p><p><a href='../manual/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Coiled coil

<p>Provides information about the sequence similarity with other proteins.</p><p><a href='../manual/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Phylogenomic databases

Family and domain databases

<p>Displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including length and molecular weight.</p><p><a href='../manual/sequences_section' target='_top'>More...</a></p>Sequences (2)i

Natural variant

Alternative sequence

Sequence databases

Genome annotation databases

<p>Is used to point to information related to entries and found in data collections other than UniProtKB.</p><p><a href='../manual/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Polymorphism and mutation databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>Provides general information on the entry.</p><p><a href='../manual/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>Contains any relevant information that doesn’t fit in any other defined sections</p><p><a href='../manual/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Documents

Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

GO - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Expressionⁱ

Interactionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Sequences (2)ⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ