ID   TRPM3_HUMAN             Reviewed;        1732 AA.
AC   Q9HCF6; A2A3F6; A9Z1Y7; Q5VW02; Q5VW03; Q5VW04; Q5W5T7; Q86SH0; Q86SH6;
AC   Q86UL0; Q86WK1; Q86WK2; Q86WK3; Q86WK4; Q86YZ9; Q86Z00; Q86Z01; Q9H0X2;
DT   10-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT   08-FEB-2011, sequence version 4.
DT   27-MAR-2024, entry version 167.
DE   RecName: Full=Transient receptor potential cation channel subfamily M member 3;
DE   AltName: Full=Long transient receptor potential channel 3;
DE            Short=LTrpC-3;
DE            Short=LTrpC3;
DE   AltName: Full=Melastatin-2;
DE            Short=MLSN2;
GN   Name=TRPM3; Synonyms=KIAA1616, LTRPC3;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 10), FUNCTION, AND TISSUE
RP   SPECIFICITY.
RC   TISSUE=Fetal brain;
RX   PubMed=12672799; DOI=10.1074/jbc.m300945200;
RA   Grimm C., Kraft R., Sauerbruch S., Schultz G., Harteneck C.;
RT   "Molecular and functional characterization of the melastatin-related cation
RT   channel TRPM3.";
RL   J. Biol. Chem. 278:21493-21501(2003).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15164053; DOI=10.1038/nature02465;
RA   Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA   Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA   Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA   Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA   Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA   Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA   Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA   Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA   Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA   Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA   Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA   Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA   Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA   Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA   Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA   Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA   Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA   Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA   McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA   Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA   Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA   Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA   Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA   West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA   Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA   Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA   Dunham I.;
RT   "DNA sequence and analysis of human chromosome 9.";
RL   Nature 429:369-374(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 12).
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-324 (ISOFORM 11).
RC   TISSUE=Amygdala;
RX   PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA   Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA   Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA   Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA   Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA   Klein M., Poustka A.;
RT   "Towards a catalog of human genes and proteins: sequencing and analysis of
RT   500 novel complete protein coding human cDNAs.";
RL   Genome Res. 11:422-435(2001).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 154-1732 (ISOFORMS 1; 2; 3; 4; 5 AND 6),
RP   VARIANT THR-1732, FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=12672827; DOI=10.1074/jbc.m211232200;
RA   Lee N., Chen J., Sun L., Wu S., Gray K.R., Rich A., Huang M., Lin J.-H.,
RA   Feder J.N., Janovitz E.B., Levesque P.C., Blanar M.A.;
RT   "Expression and characterization of human transient receptor potential
RT   melastatin 3 (hTRPM3).";
RL   J. Biol. Chem. 278:20890-20897(2003).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 154-1732 (ISOFORMS 1; 2; 4; 7 AND
RP   8), AND VARIANT THR-1732.
RC   TISSUE=Brain;
RA   Okabayashi K., Hirano K., Sano M., Murahashi Y., Miyauchi A., Gonoi T.;
RT   "ProX human full-length cDNA cloning project.";
RL   Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 716-1732 (ISOFORMS
RP   1/2/3/4/5/7/8), AND VARIANTS LYS-1717 AND THR-1732.
RC   TISSUE=Brain;
RX   PubMed=10997877; DOI=10.1093/dnares/7.4.271;
RA   Nagase T., Kikuno R., Nakayama M., Hirosawa M., Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. XVIII. The
RT   complete sequences of 100 new cDNA clones from brain which code for large
RT   proteins in vitro.";
RL   DNA Res. 7:273-281(2000).
RN   [8]
RP   FUNCTION, IDENTIFICATION IN COMPLEX WITH TRPM3, AND SUBCELLULAR LOCATION.
RX   PubMed=21278253; DOI=10.1074/jbc.m110.202945;
RA   Lambert S., Drews A., Rizun O., Wagner T.F., Lis A., Mannebach S.,
RA   Plant S., Portz M., Meissner M., Philipp S.E., Oberwinkler J.;
RT   "Transient receptor potential melastatin 1 (TRPM1) is an ion-conducting
RT   plasma membrane channel inhibited by zinc ions.";
RL   J. Biol. Chem. 286:12221-12233(2011).
RN   [9]
RP   VARIANT CTRCT50 MET-65, AND INVOLVEMENT IN CTRCT50.
RX   PubMed=25090642; DOI=10.1371/journal.pone.0104000;
RA   Bennett T.M., Mackay D.S., Siegfried C.J., Shiels A.;
RT   "Mutation of the melastatin-related cation channel, TRPM3, underlies
RT   inherited cataract and glaucoma.";
RL   PLoS ONE 9:e104000-e104000(2014).
RN   [10]
RP   VARIANTS NEDFSS MET-1015 AND GLN-1115, AND INVOLVEMENT IN NEDFSS.
RX   PubMed=31278393; DOI=10.1038/s41431-019-0462-x;
RA   Dyment D.A., Terhal P.A., Rustad C.F., Tveten K., Griffith C., Jayakar P.,
RA   Shinawi M., Ellingwood S., Smith R., van Gassen K., McWalter K.,
RA   Innes A.M., Lines M.A.;
RT   "De novo substitutions of TRPM3 cause intellectual disability and
RT   epilepsy.";
RL   Eur. J. Hum. Genet. 27:1611-1618(2019).
RN   [11]
RP   CHARACTERIZATION OF VARIANTS NEDFSS MET-1015 AND GLN-1115.
RX   PubMed=32427099; DOI=10.7554/elife.57190;
RA   Van Hoeymissen E., Held K., Nogueira Freitas A.C., Janssens A., Voets T.,
RA   Vriens J.;
RT   "Gain of channel function and modified gating properties in TRPM3 mutants
RT   causing intellectual disability and epilepsy.";
RL   Elife 9:0-0(2020).
RN   [12]
RP   CHARACTERIZATION OF VARIANTS NEDFSS MET-1015 AND GLN-1115.
RX   PubMed=32343227; DOI=10.7554/elife.55634;
RA   Zhao S., Yudin Y., Rohacs T.;
RT   "Disease-associated mutations in the human TRPM3 render the channel
RT   overactive via two distinct mechanisms.";
RL   Elife 9:0-0(2020).
RN   [13]
RP   VARIANT NEDFSS MET-1015.
RX   PubMed=32439617; DOI=10.1016/j.ejmg.2020.103942;
RA   de Sainte Agathe J.M., Van-Gils J., Lasseaux E., Arveiler B., Lacombe D.,
RA   Pfirrmann C., Raclet V., Gaston L., Plaisant C., Aupy J., Trimouille A.;
RT   "Confirmation and Expansion of the Phenotype Associated with the Recurrent
RT   p.Val837Met Variant in TRPM3.";
RL   Eur. J. Med. Genet. 63:103942-103942(2020).
RN   [14]
RP   VARIANT NEDFSS THR-1380.
RX   PubMed=34074259; DOI=10.1186/s12887-021-02719-8;
RA   Kang Q., Yang L., Liao H., Yang S., Kuang X., Ning Z., Liao C., Chen B.;
RT   "A Chinese patient with developmental and epileptic encephalopathies (DEE)
RT   carrying a TRPM3 gene mutation: a paediatric case report.";
RL   BMC Pediatr. 21:256-256(2021).
RN   [15]
RP   VARIANT NEDFSS MET-1015.
RX   PubMed=34438093; DOI=10.1016/j.ejmg.2021.104320;
RA   Gauthier L.W., Chatron N., Cabet S., Labalme A., Carneiro M., Poirot I.,
RA   Delvert C., Gleizal A., Lesca G., Putoux A.;
RT   "Description of a novel patient with the TRPM3 recurrent p.Val837Met
RT   variant.";
RL   Eur. J. Med. Genet. 64:104320-104320(2021).
RN   [16]
RP   VARIANT NEDFSS MET-1015.
RX   PubMed=35146895; DOI=10.1002/ajmg.a.62673;
RG   TUDP Study Group;
RA   Lines M.A., Goldenberg P., Wong A., Srivastava S., Bayat A., Hove H.,
RA   Karstensen H.G., Anyane-Yeboa K., Liao J., Jiang N., May A., Guzman E.,
RA   Morleo M., D'Arrigo S., Ciaccio C., Pantaleoni C., Castello R., McKee S.,
RA   Ong J., Zibdeh-Lough H., Tran-Mau-Them F., Gerasimenko A., Heron D.,
RA   Keren B., Margot H., de Sainte Agathe J.M., Burglen L., Voets T.,
RA   Vriens J., Innes A.M., Dyment D.A.;
RT   "Phenotypic spectrum of the recurrent TRPM3 p.(Val837Met) substitution in
RT   seven individuals with global developmental delay and hypotonia.";
RL   Am. J. Med. Genet. A 188:1667-1675(2022).
CC   -!- FUNCTION: Calcium channel mediating constitutive calcium ion entry. Its
CC       activity is increased by reduction in extracellular osmolarity, by
CC       store depletion and muscarinic receptor activation. In addition, forms
CC       heteromultimeric ion channels with TRPM1 which are permeable for
CC       calcium and zinc ions (PubMed:21278253). {ECO:0000269|PubMed:12672799,
CC       ECO:0000269|PubMed:12672827, ECO:0000269|PubMed:21278253}.
CC   -!- SUBUNIT: Interacts with TRPM1; the interaction results in the formation
CC       of a heteromultimeric cation channel complex.
CC       {ECO:0000269|PubMed:21278253}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12672827,
CC       ECO:0000305|PubMed:21278253}; Multi-pass membrane protein
CC       {ECO:0000269|PubMed:12672827}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=11;
CC       Name=1; Synonyms=TRPM3f;
CC         IsoId=Q9HCF6-1; Sequence=Displayed;
CC       Name=2; Synonyms=TRPM3a;
CC         IsoId=Q9HCF6-2; Sequence=VSP_012826;
CC       Name=3; Synonyms=TRPM3b;
CC         IsoId=Q9HCF6-3; Sequence=VSP_012826, VSP_012828;
CC       Name=4; Synonyms=TRPM3d;
CC         IsoId=Q9HCF6-4; Sequence=VSP_012826, VSP_012829;
CC       Name=5; Synonyms=TRPM3e;
CC         IsoId=Q9HCF6-5; Sequence=VSP_012826, VSP_012828, VSP_012829;
CC       Name=6; Synonyms=TRPM3c;
CC         IsoId=Q9HCF6-6; Sequence=VSP_012826, VSP_012830;
CC       Name=7;
CC         IsoId=Q9HCF6-7; Sequence=VSP_012829;
CC       Name=8;
CC         IsoId=Q9HCF6-8; Sequence=VSP_012826, VSP_012827, VSP_012829;
CC       Name=10;
CC         IsoId=Q9HCF6-10; Sequence=VSP_012826, VSP_012831, VSP_012832;
CC       Name=11;
CC         IsoId=Q9HCF6-11; Sequence=VSP_039107;
CC       Name=12;
CC         IsoId=Q9HCF6-12; Sequence=VSP_043515, VSP_012826, VSP_043516;
CC   -!- TISSUE SPECIFICITY: Expressed primarily in the kidney and, at lower
CC       levels, in brain, testis, ovary, pancreas and spinal cord. Expression
CC       in the brain and kidney was determined at protein level. In the kidney,
CC       expressed predominantly in the collecting tubular epithelium in the
CC       medulla, medullary rays, and periglomerular regions; in the brain,
CC       highest levels are found in the cerebellum, choroid plexus, the locus
CC       coeruleus, the posterior thalamus and the substantia nigra. Down-
CC       regulated in renal tumors compared to normal kidney. Expressed in the
CC       lens (PubMed:25090642). {ECO:0000269|PubMed:12672799,
CC       ECO:0000269|PubMed:12672827, ECO:0000269|PubMed:25090642}.
CC   -!- DISEASE: Neurodevelopmental disorder with hypotonia, dysmorphic facies,
CC       and skeletal anomalies, with or without seizures (NEDFSS) [MIM:620224]:
CC       An autosomal dominant disorder characterized by global developmental
CC       delay, moderate to severely impaired intellectual development, poor or
CC       absent speech, congenital hypotonia, dysmorphic facial features,
CC       exotropia, and musculoskeletal issues such as hip dysplasia, hip
CC       dislocation and scoliosis. About half of patients develop various types
CC       of seizures. {ECO:0000269|PubMed:31278393, ECO:0000269|PubMed:32343227,
CC       ECO:0000269|PubMed:32427099, ECO:0000269|PubMed:32439617,
CC       ECO:0000269|PubMed:34074259, ECO:0000269|PubMed:34438093,
CC       ECO:0000269|PubMed:35146895}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- DISEASE: Cataract 50 with or without glaucoma (CTRCT50) [MIM:620253]: A
CC       form of cataract, an opacification of the crystalline lens of the eye
CC       that frequently results in visual impairment or blindness. Opacities
CC       vary in morphology, are often confined to a portion of the lens, and
CC       may be static or progressive. In general, the more posteriorly located
CC       and dense an opacity, the greater the impact on visual function.
CC       CTRCT50 is an autosomal dominant form characterized by early onset.
CC       Affected individuals may also exhibit high-tension glaucoma and
CC       variable anterior segment defects. {ECO:0000269|PubMed:25090642}.
CC       Note=The disease is caused by variants affecting the gene represented
CC       in this entry.
CC   -!- SIMILARITY: Belongs to the transient receptor (TC 1.A.4) family. LTrpC
CC       subfamily. TRPM3 sub-subfamily. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAB66480.2; Type=Miscellaneous discrepancy; Note=Cloning artifact in C-terminus.; Evidence={ECO:0000305};
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DR   EMBL; AJ505025; CAD43604.1; -; mRNA.
DR   EMBL; AJ505026; CAD43605.1; -; mRNA.
DR   EMBL; AL159990; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL161913; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL356318; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL358786; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL442645; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL160273; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL391819; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL592438; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC121821; AAI21822.2; -; mRNA.
DR   EMBL; BC134414; AAI34415.1; -; mRNA.
DR   EMBL; BC142972; AAI42973.1; -; mRNA.
DR   EMBL; AL136545; CAB66480.2; ALT_SEQ; mRNA.
DR   EMBL; AF536748; AAO49153.1; -; mRNA.
DR   EMBL; AF536749; AAO49154.1; -; mRNA.
DR   EMBL; AF536750; AAO49155.1; -; mRNA.
DR   EMBL; AF536751; AAO49156.1; -; mRNA.
DR   EMBL; AF536752; AAO49157.1; -; mRNA.
DR   EMBL; AF536753; AAO49158.1; -; mRNA.
DR   EMBL; AB099661; BAC55102.1; -; mRNA.
DR   EMBL; AB099662; BAC55103.1; -; mRNA.
DR   EMBL; AB099663; BAC55104.1; -; mRNA.
DR   EMBL; AB099664; BAC55105.1; -; mRNA.
DR   EMBL; AB099665; BAC55106.1; -; mRNA.
DR   EMBL; AB046836; BAB13442.1; -; mRNA.
DR   CCDS; CCDS43835.1; -. [Q9HCF6-2]
DR   CCDS; CCDS6637.1; -. [Q9HCF6-12]
DR   CCDS; CCDS94419.1; -. [Q9HCF6-10]
DR   CCDS; CCDS94420.1; -. [Q9HCF6-3]
DR   RefSeq; NP_001007472.2; NM_001007471.2. [Q9HCF6-2]
DR   RefSeq; NP_996831.1; NM_206948.2. [Q9HCF6-12]
DR   RefSeq; XP_011517340.1; XM_011519038.2.
DR   RefSeq; XP_011517341.1; XM_011519039.2.
DR   RefSeq; XP_011517343.1; XM_011519041.2.
DR   RefSeq; XP_011517346.1; XM_011519044.2.
DR   RefSeq; XP_011517348.1; XM_011519046.2.
DR   RefSeq; XP_011517349.1; XM_011519047.2.
DR   RefSeq; XP_016870631.1; XM_017015142.1.
DR   AlphaFoldDB; Q9HCF6; -.
DR   SMR; Q9HCF6; -.
DR   BioGRID; 123085; 28.
DR   IntAct; Q9HCF6; 5.
DR   STRING; 9606.ENSP00000366314; -.
DR   ChEMBL; CHEMBL3559708; -.
DR   DrugBank; DB00794; Primidone.
DR   GuidetoPHARMACOLOGY; 495; -.
DR   TCDB; 1.A.4.5.6; the transient receptor potential ca2+/cation channel (trp-cc) family.
DR   GlyGen; Q9HCF6; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q9HCF6; -.
DR   PhosphoSitePlus; Q9HCF6; -.
DR   BioMuta; TRPM3; -.
DR   DMDM; 322510140; -.
DR   EPD; Q9HCF6; -.
DR   MassIVE; Q9HCF6; -.
DR   MaxQB; Q9HCF6; -.
DR   PaxDb; 9606-ENSP00000366314; -.
DR   PeptideAtlas; Q9HCF6; -.
DR   ProteomicsDB; 81697; -. [Q9HCF6-1]
DR   ProteomicsDB; 81698; -. [Q9HCF6-10]
DR   ProteomicsDB; 81699; -. [Q9HCF6-11]
DR   ProteomicsDB; 81701; -. [Q9HCF6-2]
DR   ProteomicsDB; 81702; -. [Q9HCF6-3]
DR   ProteomicsDB; 81703; -. [Q9HCF6-4]
DR   ProteomicsDB; 81704; -. [Q9HCF6-5]
DR   ProteomicsDB; 81705; -. [Q9HCF6-6]
DR   ProteomicsDB; 81706; -. [Q9HCF6-7]
DR   ProteomicsDB; 81707; -. [Q9HCF6-8]
DR   Antibodypedia; 12418; 202 antibodies from 20 providers.
DR   DNASU; 80036; -.
DR   Ensembl; ENST00000361823.9; ENSP00000355395.4; ENSG00000083067.26. [Q9HCF6-12]
DR   Ensembl; ENST00000377110.9; ENSP00000366314.4; ENSG00000083067.26. [Q9HCF6-2]
DR   Ensembl; ENST00000377111.8; ENSP00000366315.4; ENSG00000083067.26. [Q9HCF6-10]
DR   Ensembl; ENST00000677713.2; ENSP00000503830.2; ENSG00000083067.26. [Q9HCF6-3]
DR   GeneID; 80036; -.
DR   KEGG; hsa:80036; -.
DR   MANE-Select; ENST00000677713.2; ENSP00000503830.2; NM_001366145.2; NP_001353074.1. [Q9HCF6-3]
DR   UCSC; uc004aic.4; human. [Q9HCF6-1]
DR   AGR; HGNC:17992; -.
DR   CTD; 80036; -.
DR   DisGeNET; 80036; -.
DR   GeneCards; TRPM3; -.
DR   GeneReviews; TRPM3; -.
DR   HGNC; HGNC:17992; TRPM3.
DR   HPA; ENSG00000083067; Tissue enriched (choroid).
DR   MalaCards; TRPM3; -.
DR   MIM; 608961; gene.
DR   MIM; 620224; phenotype.
DR   MIM; 620253; phenotype.
DR   neXtProt; NX_Q9HCF6; -.
DR   OpenTargets; ENSG00000083067; -.
DR   Orphanet; 178469; Autosomal dominant non-syndromic intellectual disability.
DR   PharmGKB; PA38271; -.
DR   VEuPathDB; HostDB:ENSG00000083067; -.
DR   eggNOG; KOG3614; Eukaryota.
DR   GeneTree; ENSGT00940000157366; -.
DR   HOGENOM; CLU_001390_4_1_1; -.
DR   InParanoid; Q9HCF6; -.
DR   OMA; XVIRHVG; -.
DR   OrthoDB; 201873at2759; -.
DR   PhylomeDB; Q9HCF6; -.
DR   TreeFam; TF314204; -.
DR   PathwayCommons; Q9HCF6; -.
DR   Reactome; R-HSA-3295583; TRP channels.
DR   SignaLink; Q9HCF6; -.
DR   BioGRID-ORCS; 80036; 6 hits in 1150 CRISPR screens.
DR   ChiTaRS; TRPM3; human.
DR   GeneWiki; TRPM3; -.
DR   GenomeRNAi; 80036; -.
DR   Pharos; Q9HCF6; Tchem.
DR   PRO; PR:Q9HCF6; -.
DR   Proteomes; UP000005640; Chromosome 9.
DR   RNAct; Q9HCF6; Protein.
DR   Bgee; ENSG00000083067; Expressed in pigmented layer of retina and 142 other cell types or tissues.
DR   ExpressionAtlas; Q9HCF6; baseline and differential.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0005262; F:calcium channel activity; IDA:UniProtKB.
DR   GO; GO:0005261; F:monoatomic cation channel activity; IDA:MGI.
DR   GO; GO:0070588; P:calcium ion transmembrane transport; IDA:UniProtKB.
DR   GO; GO:0098655; P:monoatomic cation transmembrane transport; IBA:GO_Central.
DR   GO; GO:0006812; P:monoatomic cation transport; IDA:MGI.
DR   GO; GO:0051262; P:protein tetramerization; IEA:InterPro.
DR   Gene3D; 1.20.5.1010; TRPM, tetramerisation domain; 1.
DR   InterPro; IPR005821; Ion_trans_dom.
DR   InterPro; IPR041491; TRPM_SLOG.
DR   InterPro; IPR032415; TRPM_tetra.
DR   InterPro; IPR037162; TRPM_tetra_sf.
DR   PANTHER; PTHR13800:SF7; TRANSIENT RECEPTOR POTENTIAL CATION CHANNEL SUBFAMILY M MEMBER 3; 1.
DR   PANTHER; PTHR13800; TRANSIENT RECEPTOR POTENTIAL CATION CHANNEL, SUBFAMILY M, MEMBER 6; 1.
DR   Pfam; PF00520; Ion_trans; 1.
DR   Pfam; PF18139; LSDAT_euk; 1.
DR   Pfam; PF16519; TRPM_tetra; 1.
DR   Genevisible; Q9HCF6; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Calcium; Calcium channel; Calcium transport;
KW   Cataract; Cell membrane; Coiled coil; Disease variant; Epilepsy;
KW   Intellectual disability; Ion channel; Ion transport; Membrane;
KW   Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT   CHAIN           1..1732
FT                   /note="Transient receptor potential cation channel
FT                   subfamily M member 3"
FT                   /id="PRO_0000215328"
FT   TRANSMEM        4..24
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        25..794
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        795..815
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        816..897
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        898..918
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        919..964
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        965..985
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        986..995
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        996..1016
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1017..1028
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1029..1049
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1050..1116
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1117..1137
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1138..1732
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          1459..1478
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1611..1732
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          1241..1301
FT                   /evidence="ECO:0000255"
FT   COMPBIAS        1459..1474
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1611..1630
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1636..1658
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VAR_SEQ         1..153
FT                   /note="Missing (in isoform 12)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_043515"
FT   VAR_SEQ         1..59
FT                   /note="MPEPWGTVYFLGIAQVFSFLFSWWNLEGVMNQADAPRPLNWTIRKLCHAAFL
FT                   PSVRLLK -> MGKKWRDAAEMERGCSDREDNAESRRRSRSASRGRFAESWKRLSSKQG
FT                   STKRSGLPSQQTP (in isoform 11)"
FT                   /evidence="ECO:0000303|PubMed:11230166"
FT                   /id="VSP_039107"
FT   VAR_SEQ         326..350
FT                   /note="Missing (in isoform 2, isoform 3, isoform 4, isoform
FT                   5, isoform 6, isoform 8, isoform 10 and isoform 12)"
FT                   /evidence="ECO:0000303|PubMed:12672799,
FT                   ECO:0000303|PubMed:12672827, ECO:0000303|PubMed:15489334,
FT                   ECO:0000303|Ref.6"
FT                   /id="VSP_012826"
FT   VAR_SEQ         409..1732
FT                   /note="Missing (in isoform 12)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_043516"
FT   VAR_SEQ         535..552
FT                   /note="Missing (in isoform 8)"
FT                   /evidence="ECO:0000303|Ref.6"
FT                   /id="VSP_012827"
FT   VAR_SEQ         569
FT                   /note="K -> KREYPGFGWIYFK (in isoform 3 and isoform 5)"
FT                   /evidence="ECO:0000303|PubMed:12672827"
FT                   /id="VSP_012828"
FT   VAR_SEQ         617..626
FT                   /note="Missing (in isoform 4, isoform 5, isoform 7 and
FT                   isoform 8)"
FT                   /evidence="ECO:0000303|PubMed:12672827, ECO:0000303|Ref.6"
FT                   /id="VSP_012829"
FT   VAR_SEQ         1088
FT                   /note="P -> RKQVYDSHTPKSA (in isoform 6)"
FT                   /evidence="ECO:0000303|PubMed:12672827"
FT                   /id="VSP_012830"
FT   VAR_SEQ         1344..1350
FT                   /note="GEETMSP -> EHPLYSV (in isoform 10)"
FT                   /evidence="ECO:0000303|PubMed:12672799"
FT                   /id="VSP_012831"
FT   VAR_SEQ         1351..1732
FT                   /note="Missing (in isoform 10)"
FT                   /evidence="ECO:0000303|PubMed:12672799"
FT                   /id="VSP_012832"
FT   VARIANT         65
FT                   /note="I -> M (in CTRCT50)"
FT                   /evidence="ECO:0000269|PubMed:25090642"
FT                   /id="VAR_088074"
FT   VARIANT         1015
FT                   /note="V -> M (in NEDFSS; gain-of-function variant
FT                   resulting in increased calcium ion transmembrane transport;
FT                   basal channel activity is increased and the channel is more
FT                   sensitive to stimulation by heat or the neurosteroid
FT                   pregnenolone sulfate; the mutant channel can be
FT                   down-regulated by the TRPM3 antagonist and anti-epileptic
FT                   drug primidone)"
FT                   /evidence="ECO:0000269|PubMed:31278393,
FT                   ECO:0000269|PubMed:32343227, ECO:0000269|PubMed:32427099,
FT                   ECO:0000269|PubMed:32439617, ECO:0000269|PubMed:34438093,
FT                   ECO:0000269|PubMed:35146895"
FT                   /id="VAR_088075"
FT   VARIANT         1115
FT                   /note="P -> Q (in NEDFSS; gain-of-function variant
FT                   resulting in increased calcium ion transmembrane transport;
FT                   basal channel activity is increased and the channel is more
FT                   sensitive to stimulation by heat or the neurosteroid
FT                   pregnenolone sulfate; the mutant channel can be inhibited
FT                   by the TRPM3 antagonist and anti-epileptic drug primidone)"
FT                   /evidence="ECO:0000269|PubMed:31278393,
FT                   ECO:0000269|PubMed:32343227, ECO:0000269|PubMed:32427099"
FT                   /id="VAR_088076"
FT   VARIANT         1380
FT                   /note="S -> T (in NEDFSS; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:34074259"
FT                   /id="VAR_088077"
FT   VARIANT         1653
FT                   /note="T -> I (in dbSNP:rs13440436)"
FT                   /id="VAR_057305"
FT   VARIANT         1695
FT                   /note="R -> Q (in dbSNP:rs6560142)"
FT                   /id="VAR_021257"
FT   VARIANT         1717
FT                   /note="R -> K (in dbSNP:rs41287373)"
FT                   /evidence="ECO:0000269|PubMed:10997877"
FT                   /id="VAR_061862"
FT   VARIANT         1732
FT                   /note="N -> T (in dbSNP:rs17535963)"
FT                   /evidence="ECO:0000269|PubMed:10997877,
FT                   ECO:0000269|PubMed:12672827, ECO:0000269|Ref.6"
FT                   /id="VAR_057306"
FT   CONFLICT        335
FT                   /note="R -> H (in Ref. 6; BAC55103)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        695
FT                   /note="C -> Y (in Ref. 6; BAC55106)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1032
FT                   /note="D -> E (in Ref. 6; BAC55106)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1730
FT                   /note="K -> Q (in Ref. 6; BAC55104)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1732 AA;  197571 MW;  0D6BE312C56646A4 CRC64;
     MPEPWGTVYF LGIAQVFSFL FSWWNLEGVM NQADAPRPLN WTIRKLCHAA FLPSVRLLKA
     QKSWIERAFY KRECVHIIPS TKDPHRCCCG RLIGQHVGLT PSISVLQNEK NESRLSRNDI
     QSEKWSISKH TQLSPTDAFG TIEFQGGGHS NKAMYVRVSF DTKPDLLLHL MTKEWQLELP
     KLLISVHGGL QNFELQPKLK QVFGKGLIKA AMTTGAWIFT GGVNTGVIRH VGDALKDHAS
     KSRGKICTIG IAPWGIVENQ EDLIGRDVVR PYQTMSNPMS KLTVLNSMHS HFILADNGTT
     GKYGAEVKLR RQLEKHISLQ KINTRCLPFF SLDSRLFYSF WGSCQLDSVG IGQGVPVVAL
     IVEGGPNVIS IVLEYLRDTP PVPVVVCDGS GRASDILAFG HKYSEEGGLI NESLRDQLLV
     TIQKTFTYTR TQAQHLFIIL MECMKKKELI TVFRMGSEGH QDIDLAILTA LLKGANASAP
     DQLSLALAWN RVDIARSQIF IYGQQWPVGS LEQAMLDALV LDRVDFVKLL IENGVSMHRF
     LTISRLEELY NTRHGPSNTL YHLVRDVKKG NLPPDYRISL IDIGLVIEYL MGGAYRCNYT
     RKRFRTLYHN LFGPKRPKAL KLLGMEDDIP LRRGRKTTKK REEEVDIDLD DPEINHFPFP
     FHELMVWAVL MKRQKMALFF WQHGEEAMAK ALVACKLCKA MAHEASENDM VDDISQELNH
     NSRDFGQLAV ELLDQSYKQD EQLAMKLLTY ELKNWSNATC LQLAVAAKHR DFIAHTCSQM
     LLTDMWMGRL RMRKNSGLKV ILGILLPPSI LSLEFKNKDD MPYMSQAQEI HLQEKEAEEP
     EKPTKEKEEE DMELTAMLGR NNGESSRKKD EEEVQSKHRL IPLGRKIYEF YNAPIVKFWF
     YTLAYIGYLM LFNYIVLVKM ERWPSTQEWI VISYIFTLGI EKMREILMSE PGKLLQKVKV
     WLQEYWNVTD LIAILLFSVG MILRLQDQPF RSDGRVIYCV NIIYWYIRLL DIFGVNKYLG
     PYVMMIGKMM IDMMYFVIIM LVVLMSFGVA RQAILFPNEE PSWKLAKNIF YMPYWMIYGE
     VFADQIDPPC GQNETREDGK IIQLPPCKTG AWIVPAIMAC YLLVANILLV NLLIAVFNNT
     FFEVKSISNQ VWKFQRYQLI MTFHERPVLP PPLIIFSHMT MIFQHLCCRW RKHESDPDER
     DYGLKLFITD DELKKVHDFE EQCIEEYFRE KDDRFNSSND ERIRVTSERV ENMSMRLEEV
     NEREHSMKAS LQTVDIRLAQ LEDLIGRMAT ALERLTGLER AESNKIRSRT SSDCTDAAYI
     VRQSSFNSQE GNTFKLQESI DPAGEETMSP TSPTLMPRMR SHSFYSVNMK DKGGIEKLES
     IFKERSLSLH RATSSHSVAK EPKAPAAPAN TLAIVPDSRR PSSCIDIYVS AMDELHCDID
     PLDNSVNILG LGEPSFSTPV PSTAPSSSAY ATLAPTDRPP SRSIDFEDIT SMDTRSFSSD
     YTHLPECQNP WDSEPPMYHT IERSKSSRYL ATTPFLLEEA PIVKSHSFMF SPSRSYYANF
     GVPVKTAEYT SITDCIDTRC VNAPQAIADR AAFPGGLGDK VEDLTCCHPE REAELSHPSS
     DSEENEAKGR RATIAISSQE GDNSERTLSN NITVPKIERA NSYSAEEPSA PYAHTRKSFS
     ISDKLDRQRN TASLRNPFQR SKSSKPEGRG DSLSMRRLSR TSAFQSFESK HN
//