Protein

Cystic fibrosis transmembrane conductance regulator

Gene

CFTR

Organism

Homo sapiens (Human)

Status

Reviewed-Annotation score: -Experimental evidence at protein levelⁱ

Functionⁱ

Epithelial ion channel that plays an important role in the regulation of epithelial ion and water transport and fluid homeostasis (PubMed:26823428). Mediates the transport of chloride ions across the cell membrane (PubMed:10792060, PubMed:11524016, PubMed:11707463, PubMed:12519745, PubMed:15010471, PubMed:12588899, PubMed:17036051, PubMed:19398555, PubMed:19621064, PubMed:22178883, PubMed:25330774, PubMed:1712898, PubMed:8910473, PubMed:9804160, PubMed:12529365, PubMed:17182731, PubMed:26846474, PubMed:28087700). Channel activity is coupled to ATP hydrolysis (PubMed:8910473). The ion channel is also permeable to HCO^3-; selectivity depends on the extracellular chloride concentration (PubMed:15010471, PubMed:19019741). Exerts its function also by modulating the activity of other ion channels and transporters (PubMed:12403779, PubMed:22178883, PubMed:22121115, PubMed:27941075). Plays an important role in airway fluid homeostasis (PubMed:16645176, PubMed:19621064, PubMed:26823428). Contributes to the regulation of the pH and the ion content of the airway surface fluid layer and thereby plays an important role in defense against pathogens (PubMed:14668433, PubMed:16645176, PubMed:26823428). Modulates the activity of the epithelial sodium channel (ENaC) complex, in part by regulating the cell surface expression of the ENaC complex (PubMed:17434346, PubMed:27941075, PubMed:17182731). Inhibits the activity of the ENaC channel containing subunits SCNN1A, SCNN1B and SCNN1G (PubMed:17182731). Inhibits the activity of the ENaC channel containing subunits SCNN1D, SCNN1B and SCNN1G, but not of the ENaC channel containing subunits SCNN1A, SCNN1B and SCNN1G (PubMed:27941075). May regulate bicarbonate secretion and salvage in epithelial cells by regulating the transporter SLC4A7 (PubMed:12403779). Can inhibit the chloride channel activity of ANO1 (PubMed:22178883). Plays a role in the chloride and bicarbonate homeostasis during sperm epididymal maturation and capacitation (PubMed:19923167, PubMed:27714810).1 Publication26 Publications

Catalytic activityⁱ

ATP
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H₂O
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=
ADP
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+
H⁺
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phosphate
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4 Publications
Manual assertion based on experiment inⁱ
- Ref.11
  "A monomer is the minimum functional unit required for channel and ATPase activity of the cystic fibrosis transmembrane conductance regulator."
  Ramjeesingh M., Li C., Kogan I., Wang Y., Huan L.J., Bear C.E.
  Biochemistry 40:10700-10706(2001) [PubMed] [Europe PMC] [Abstract]
  Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, SUBUNIT.
- Ref.21
  "A heteromeric complex of the two nucleotide binding domains of cystic fibrosis transmembrane conductance regulator (CFTR) mediates ATPase activity."
  Kidd J.F., Ramjeesingh M., Stratford F., Huan L.J., Bear C.E.
  J. Biol. Chem. 279:41664-41669(2004) [PubMed] [Europe PMC] [Abstract]
  Cited for: CATALYTIC ACTIVITY, DOMAIN.
- Ref.40
  "Channel gating regulation by the cystic fibrosis transmembrane conductance regulator (CFTR) first cytosolic loop."
  Ehrhardt A., Chung W.J., Pyle L.C., Wang W., Nowotarski K., Mulvihill C.M., Ramjeesingh M., Hong J., Velu S.E., Lewis H.A., Atwell S., Aller S., Bear C.E., Lukacs G.L., Kirk K.L., Sorscher E.J.
  J. Biol. Chem. 291:1854-1865(2016) [PubMed] [Europe PMC] [Abstract]
  Cited for: CATALYTIC ACTIVITY, FUNCTION.
- Ref.96
  "ATPase activity of the cystic fibrosis transmembrane conductance regulator."
  Li C., Ramjeesingh M., Wang W., Garami E., Hewryk M., Lee D., Rommens J.M., Galley K., Bear C.E.
  J. Biol. Chem. 271:28463-28468(1996) [PubMed] [Europe PMC] [Abstract]
  Cited for: CHARACTERIZATION OF VARIANT CF ASP-551, CATALYTIC ACTIVITY, FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION.
EC:3.6.3.49
4 Publications
Manual assertion based on experiment inⁱ
- Ref.11
  "A monomer is the minimum functional unit required for channel and ATPase activity of the cystic fibrosis transmembrane conductance regulator."
  Ramjeesingh M., Li C., Kogan I., Wang Y., Huan L.J., Bear C.E.
  Biochemistry 40:10700-10706(2001) [PubMed] [Europe PMC] [Abstract]
  Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, SUBUNIT.
- Ref.21
  "A heteromeric complex of the two nucleotide binding domains of cystic fibrosis transmembrane conductance regulator (CFTR) mediates ATPase activity."
  Kidd J.F., Ramjeesingh M., Stratford F., Huan L.J., Bear C.E.
  J. Biol. Chem. 279:41664-41669(2004) [PubMed] [Europe PMC] [Abstract]
  Cited for: CATALYTIC ACTIVITY, DOMAIN.
- Ref.40
  "Channel gating regulation by the cystic fibrosis transmembrane conductance regulator (CFTR) first cytosolic loop."
  Ehrhardt A., Chung W.J., Pyle L.C., Wang W., Nowotarski K., Mulvihill C.M., Ramjeesingh M., Hong J., Velu S.E., Lewis H.A., Atwell S., Aller S., Bear C.E., Lukacs G.L., Kirk K.L., Sorscher E.J.
  J. Biol. Chem. 291:1854-1865(2016) [PubMed] [Europe PMC] [Abstract]
  Cited for: CATALYTIC ACTIVITY, FUNCTION.
- Ref.96
  "ATPase activity of the cystic fibrosis transmembrane conductance regulator."
  Li C., Ramjeesingh M., Wang W., Garami E., Hewryk M., Lee D., Rommens J.M., Galley K., Bear C.E.
  J. Biol. Chem. 271:28463-28468(1996) [PubMed] [Europe PMC] [Abstract]
  Cited for: CHARACTERIZATION OF VARIANT CF ASP-551, CATALYTIC ACTIVITY, FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION.
Source:
Rhea
Search for this reaction in UniProtKB.
See the description of this reaction in Rhea.
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H₂O
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ADP
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H⁺
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Sites

Feature key	Position(s)	DescriptionActions	Length
Binding siteⁱ	401	ATP 1Combined sources2 Publications	1
Binding siteⁱ	434	ATP 1Combined sources1 Publication	1
Binding siteⁱ	493	ATP 1Combined sources1 Publication	1
Binding siteⁱ	1219	ATP 2Combined sources	1

Regions

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Nucleotide bindingⁱ	458 – 465	ATP 1PROSITE-ProRule annotationCombined sources1 Publication		8
Nucleotide bindingⁱ	1244 – 1251	ATP 2PROSITE-ProRule annotationCombined sources		8

GO - Molecular functionⁱ

ATPase activity
Source: UniProtKB
Inferred from direct assayⁱ
- 11524016
- 8910473
ATPase activity, coupled to transmembrane movement of substances
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
ATPase-coupled anion transmembrane transporter activity Source: Reactome
ATP binding
Source: ProtInc
Traceable author statementⁱ
- 2475911
bicarbonate transmembrane transporter activity
Source: UniProtKB
Inferred from direct assayⁱ
- 15010471
- 19019741
chaperone binding
Source: ARUK-UCL
Inferred from physical interactionⁱ
- 16207813
chloride channel activity
Source: UniProtKB
Inferred from direct assayⁱ
chloride channel inhibitor activity
Source: UniProtKB
Inferred from direct assayⁱ
- 22178883
chloride channel regulator activity Source: Reactome
chloride transmembrane transporter activity Source: UniProtKB
enzyme binding
Source: UniProtKB
Inferred from physical interactionⁱ
- 19398555
intracellularly ATP-gated chloride channel activity
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 8910473
PDZ domain binding
Source: UniProtKB
Inferred from direct assayⁱ
- 11707463
Sec61 translocon complex binding
Source: UniProtKB
Inferred from direct assayⁱ
- 9792704

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

bicarbonate transport
Source: UniProtKB
Inferred from direct assayⁱ
- 15010471
- 19019741
cellular response to cAMP Source: UniProtKB
cellular response to forskolin
Source: UniProtKB
Inferred from direct assayⁱ
- 15010471
- 19621064
chloride transmembrane transport
Source: UniProtKB
Inferred from direct assayⁱ
cholesterol biosynthetic process Source: Ensembl
cholesterol transport Source: Ensembl
intracellular pH elevation Source: UniProtKB
membrane hyperpolarization Source: UniProtKB
membrane organization Source: Reactome
multicellular organismal water homeostasis
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 19621064
positive regulation of cyclic nucleotide-gated ion channel activity
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 24885604
positive regulation of exocytosis
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 24885604
positive regulation of insulin secretion involved in cellular response to glucose stimulus
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 24885604
positive regulation of voltage-gated chloride channel activity
Source: UniProtKB
Inferred from direct assayⁱ
- 22006324
protein deubiquitination Source: Reactome
response to endoplasmic reticulum stress
Source: UniProtKB
Inferred from direct assayⁱ
- 21884936
- 28067262
sperm capacitation Source: UniProtKB
transepithelial water transport
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 19621064
transmembrane transport
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
vesicle docking involved in exocytosis Source: Ensembl

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Chloride channel, Hydrolase, Ion channel
Biological process	Ion transport, Transport
Ligand	ATP-binding, Chloride, Nucleotide-binding

Enzyme and pathway databases

BioCycⁱ	MetaCyc:HS00075-MONOMER
BRENDAⁱ	3.6.3.49 2681
Reactomeⁱ	R-HSA-382556 ABC-family proteins mediated transport R-HSA-5627083 RHO GTPases regulate CFTR trafficking R-HSA-5678895 Defective CFTR causes cystic fibrosis R-HSA-5689880 Ub-specific processing proteases R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis R-HSA-8856828 Clathrin-mediated endocytosis
SIGNORⁱ	P13569

Protein family/group databases

MoonProtⁱ	P13569
TCDBⁱ	3.A.1.202.1 the atp-binding cassette (abc) superfamily

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Cystic fibrosis transmembrane conductance regulator Short name: CFTR Alternative name(s): ATP-binding cassette sub-family C member 7 Channel conductance-controlling ATPase (EC:3.6.3.494 Publications) cAMP-dependent chloride channel
Gene namesⁱ	Name:CFTR Synonyms:ABCC7
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 7

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000001626.14
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:1884 CFTR
MIMⁱ	602421 gene
neXtProtⁱ	NX_P13569

Topology

Feature key	Position(s)	DescriptionActions	Length
Topological domainⁱ	1 – 77	CytoplasmicCuratedAdd BLAST	77
Transmembraneⁱ	78 – 98	Helical; Name=11 PublicationAdd BLAST	21
Topological domainⁱ	99 – 122	Extracellular1 PublicationAdd BLAST	24
Transmembraneⁱ	123 – 146	Helical; Name=21 PublicationAdd BLAST	24
Topological domainⁱ	147 – 195	Cytoplasmic1 PublicationAdd BLAST	49
Transmembraneⁱ	196 – 216	Helical; Name=31 PublicationAdd BLAST	21
Topological domainⁱ	217 – 222	Extracellular1 Publication	6
Transmembraneⁱ	223 – 243	Helical; Name=41 PublicationAdd BLAST	21
Topological domainⁱ	244 – 298	Cytoplasmic1 PublicationAdd BLAST	55
Transmembraneⁱ	299 – 319	Helical; Name=51 PublicationAdd BLAST	21
Topological domainⁱ	320 – 339	Extracellular1 PublicationAdd BLAST	20
Transmembraneⁱ	340 – 358	Helical; Name=61 PublicationAdd BLAST	19
Topological domainⁱ	359 – 858	Cytoplasmic1 PublicationAdd BLAST	500
Transmembraneⁱ	859 – 879	Helical; Name=71 PublicationAdd BLAST	21
Topological domainⁱ	880 – 918	Extracellular1 PublicationAdd BLAST	39
Transmembraneⁱ	919 – 939	Discontinuously helical; Name=81 PublicationAdd BLAST	21
Topological domainⁱ	940 – 990	Cytoplasmic1 PublicationAdd BLAST	51
Transmembraneⁱ	991 – 1011	Helical; Name=91 PublicationAdd BLAST	21
Topological domainⁱ	1012 – 1013	Extracellular1 Publication	2
Transmembraneⁱ	1014 – 1034	Helical; Name=101 PublicationAdd BLAST	21
Topological domainⁱ	1035 – 1095	Cytoplasmic1 PublicationAdd BLAST	61
Transmembraneⁱ	1096 – 1116	Helical; Name=111 PublicationAdd BLAST	21
Topological domainⁱ	1117 – 1130	Extracellular1 PublicationAdd BLAST	14
Transmembraneⁱ	1131 – 1151	Helical; Name=121 PublicationAdd BLAST	21
Topological domainⁱ	1152 – 1480	Cytoplasmic1 PublicationAdd BLAST	329

Keywords - Cellular componentⁱ

Cell membrane, Endoplasmic reticulum, Endosome, Membrane, Nucleus

Pathology & Biotechⁱ

Involvement in diseaseⁱ

Cystic fibrosis (CF)72 Publications

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

Disease descriptionA common generalized disorder of the exocrine glands which impairs clearance of secretions in a variety of organs. It is characterized by the triad of chronic bronchopulmonary disease (with recurrent respiratory infections), pancreatic insufficiency (which leads to malabsorption and growth retardation) and elevated sweat electrolytes. It is the most common genetic disease in Caucasians, with a prevalence of about 1 in 2'000 live births. Inheritance is autosomal recessive.

See also OMIM:219700

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_000101	13	S → F in CF. 1 PublicationCorresponds to variant dbSNP:rs397508635EnsemblClinVar.	1
Natural variantⁱVAR_000103	31	R → L in CF. 1 PublicationCorresponds to variant dbSNP:rs149353983EnsemblClinVar.	1
Natural variantⁱVAR_000104	42	S → F in CF. 1 PublicationCorresponds to variant dbSNP:rs143456784EnsemblClinVar.	1
Natural variantⁱVAR_000105	44	D → G in CF; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1800074EnsemblClinVar.	1
Natural variantⁱVAR_000108	57	W → G in CF. 1 PublicationCorresponds to variant dbSNP:rs397508272EnsemblClinVar.	1
Natural variantⁱVAR_000109	67	P → L in CF. Corresponds to variant dbSNP:rs368505753EnsemblClinVar.	1
Natural variantⁱVAR_000110	74	R → W in CF and CBAVD. 1 PublicationCorresponds to variant dbSNP:rs115545701EnsemblClinVar.	1
Natural variantⁱVAR_000112	85	G → E in CF. 1 PublicationCorresponds to variant dbSNP:rs75961395EnsemblClinVar.	1
Natural variantⁱVAR_000113	87	F → L in CF. 1 PublicationCorresponds to variant dbSNP:rs397508403EnsemblClinVar.	1
Natural variantⁱVAR_000114	91	G → R in CF. Corresponds to variant dbSNP:rs121908750EnsemblClinVar.	1
Natural variantⁱVAR_000115	92	E → K in CF. 2 PublicationsCorresponds to variant dbSNP:rs121908751EnsemblClinVar.	1
Natural variantⁱVAR_000116	98	Q → R in CF. 1 PublicationCorresponds to variant dbSNP:rs397508464EnsemblClinVar.	1
Natural variantⁱVAR_000117	105	I → S in CF.	1
Natural variantⁱVAR_000118	109	Y → C in CF. 1 PublicationCorresponds to variant dbSNP:rs121909031EnsemblClinVar.	1
Natural variantⁱVAR_000119	110	D → H in CF and CBAVD; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs113993958EnsemblClinVar.	1
Natural variantⁱVAR_000121	117	R → C in CF. 1 PublicationCorresponds to variant dbSNP:rs77834169EnsemblClinVar.	1
Natural variantⁱVAR_000122	117	R → H in CF and CBAVD; strong decrease in single channel conductance; promotes rapid return to the closed state of the channel; decrease in bicarbonate transport. 4 PublicationsCorresponds to variant dbSNP:rs78655421EnsemblClinVar.	1
Natural variantⁱVAR_000123	117	R → L in CF. 1 PublicationCorresponds to variant dbSNP:rs78655421EnsemblClinVar.	1
Natural variantⁱVAR_000124	117	R → P in CF. 1 PublicationCorresponds to variant dbSNP:rs78655421EnsemblClinVar.	1
Natural variantⁱVAR_000125	120	A → T in CF. 1 PublicationCorresponds to variant dbSNP:rs201958172EnsemblClinVar.	1
Natural variantⁱVAR_000126	139	H → R in CF. 1 PublicationCorresponds to variant dbSNP:rs76371115EnsemblClinVar.	1
Natural variantⁱVAR_000127	141	A → D in CF. 1 PublicationCorresponds to variant dbSNP:rs397508700EnsemblClinVar.	1
Natural variantⁱVAR_000128	148	I → T in CF; unknown pathological significance; found in compound heterozygous patients bearing a severe CF mutation in trans; loss of bicarbonate transport; decreased inhibition of epithelial sodium channel (ENaC), when tested in a heterologous system; no effect on protein maturation, subcellular location at the plasma membrane, nor on chloride channel activity. 3 PublicationsCorresponds to variant dbSNP:rs35516286EnsemblClinVar.	1
Natural variantⁱVAR_000130	178	G → R in CF; loss of bicarbonate transport; no effect on protein maturation, subcellular location at the plasma membrane, nor on chloride channel activity. 2 PublicationsCorresponds to variant dbSNP:rs80282562EnsemblClinVar.	1
Natural variantⁱVAR_000131	192	Missing in CF. 1 Publication	1
Natural variantⁱVAR_000132	193	E → K in CBAVD and CF; decrease in bicarbonate transport; no effect on chloride channel activity. 3 PublicationsCorresponds to variant dbSNP:rs397508759EnsemblClinVar.	1
Natural variantⁱVAR_000133	199	H → Q in CF. Corresponds to variant dbSNP:rs397508765EnsemblClinVar.	1
Natural variantⁱVAR_000134	199	H → Y in CF. 1 PublicationCorresponds to variant dbSNP:rs121908802EnsemblClinVar.	1
Natural variantⁱVAR_000135	205	P → S in CF. 1 PublicationCorresponds to variant dbSNP:rs121908803EnsemblClinVar.	1
Natural variantⁱVAR_000136	206	L → W in CF and CBAVD. 2 PublicationsCorresponds to variant dbSNP:rs121908752EnsemblClinVar.	1
Natural variantⁱVAR_080302	220 – 1480	Missing in CF. 1 PublicationAdd BLAST	1261
Natural variantⁱVAR_000137	225	C → R in CF; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs397508780EnsemblClinVar.	1
Natural variantⁱVAR_000140	287	N → Y in CF; decreased presence at the cell membrane due to increased internalization from the apical cell membrane; no effect on single channel gating and conductance. 2 PublicationsCorresponds to variant dbSNP:rs397508804EnsemblClinVar.	1
Natural variantⁱVAR_000141	297	R → Q in CF. Corresponds to variant dbSNP:rs143486492EnsemblClinVar.	1
Natural variantⁱVAR_000142	301	Y → C in CF. Corresponds to variant dbSNP:rs150691494EnsemblClinVar.	1
Natural variantⁱVAR_000143	307	S → N in CF. Corresponds to variant dbSNP:rs397508817EnsemblClinVar.	1
Natural variantⁱVAR_000144	311	F → L in CF. Corresponds to variant dbSNP:rs121909016EnsemblClinVar.	1
Natural variantⁱVAR_000145	311	Missing in CF. 1 Publication	1
Natural variantⁱVAR_000146	314	G → E in CF. Corresponds to variant dbSNP:rs75763344EnsemblClinVar.	1
Natural variantⁱVAR_000147	314	G → R in CF. 1 PublicationCorresponds to variant dbSNP:rs397508819EnsemblClinVar.	1
Natural variantⁱVAR_000148	334	R → W in CF and CBAVD; mild; does not prevent maturation of glycans. 3 PublicationsCorresponds to variant dbSNP:rs121909011EnsemblClinVar.	1
Natural variantⁱVAR_000150	336	I → K in CF. Corresponds to variant dbSNP:rs397508139EnsemblClinVar.	1
Natural variantⁱVAR_000151	338	T → I in CF; mild; isolated hypotonic dehydration. 2 PublicationsCorresponds to variant dbSNP:rs77409459EnsemblClinVar.	1
Natural variantⁱVAR_000152	346	L → P in CF; dominant mutation but mild phenotype. 1 PublicationCorresponds to variant dbSNP:rs397508146EnsemblClinVar.	1
Natural variantⁱVAR_000153	347	R → H in CF. Corresponds to variant dbSNP:rs77932196EnsemblClinVar.	1
Natural variantⁱVAR_000154	347	R → L in CF. Corresponds to variant dbSNP:rs77932196EnsemblClinVar.	1
Natural variantⁱVAR_000155	347	R → P in CF; MILD. Corresponds to variant dbSNP:rs77932196EnsemblClinVar.	1
Natural variantⁱVAR_000156	352	R → Q in CF. Corresponds to variant dbSNP:rs121908753EnsemblClinVar.	1
Natural variantⁱVAR_000158	359 – 360	QT → KK in CF. Corresponds to variant dbSNP:rs397508152Ensembl.	2
Natural variantⁱVAR_000157	359	Q → K in CF. Corresponds to variant dbSNP:rs76879328EnsemblClinVar.	1
Natural variantⁱVAR_000159	370	K → KNK in CF. 1 Publication	1
Natural variantⁱVAR_000160	455	A → E in CF. 1 PublicationCorresponds to variant dbSNP:rs74551128EnsemblClinVar.	1
Natural variantⁱVAR_000161	456	V → F in CF. Corresponds to variant dbSNP:rs397508195EnsemblClinVar.	1
Natural variantⁱVAR_000162	458	G → V in CF. Corresponds to variant dbSNP:rs121909009EnsemblClinVar.	1
Natural variantⁱVAR_000165	480	G → C in CF. Corresponds to variant dbSNP:rs79282516EnsemblClinVar.	1
Natural variantⁱVAR_000166	492	S → F in CF. Corresponds to variant dbSNP:rs121909017EnsemblClinVar.	1
Natural variantⁱVAR_000167	504	E → Q in CF. Corresponds to variant dbSNP:rs397508223EnsemblClinVar.	1
Natural variantⁱVAR_000170	507	Missing in CF; impaired maturation of glycan chains. 2 Publications	1
Natural variantⁱVAR_000171	508	Missing in CF and CBAVD; most common mutation in Caucasian CF chromosomes; impairs protein folding and stability; causes local changes to the surface that mediates interactions between domains; decreases frequency of channel opening in vitro; impairs maturation and trafficking to the cell membrane; impairs recycling to the cell membrane after endocytosis. 18 Publications	1
Natural variantⁱVAR_000174	520	V → F in CF. 1 PublicationCorresponds to variant dbSNP:rs77646904EnsemblClinVar.	1
Natural variantⁱVAR_080305	542 – 1480	Missing in CF. 1 PublicationAdd BLAST	939
Natural variantⁱVAR_000177	549	S → I in CF; impaired maturation of glycan chains. 2 PublicationsCorresponds to variant dbSNP:rs121908755EnsemblClinVar.	1
Natural variantⁱVAR_000176	549	S → N in CF. Corresponds to variant dbSNP:rs121908755EnsemblClinVar.	1
Natural variantⁱVAR_000178	549	S → R in CF; impaired maturation of glycan chains. 1 PublicationCorresponds to variant dbSNP:rs121909005EnsemblClinVar.	1
Natural variantⁱVAR_000179	551	G → D in CF; decrease in the frequency of channel opening in vitro; decrease in channel activity and ATPase activity; complete loss of bicarbonate transport; no effect on trafficking to the cell membrane, protein stability, nor on the maturation of glycans. 8 PublicationsCorresponds to variant dbSNP:rs75527207EnsemblClinVar.	1
Natural variantⁱVAR_000180	551	G → S in CF; decrease in bicarbonate transport; no effect on chloride channel activity. 1 PublicationCorresponds to variant dbSNP:rs121909013EnsemblClinVar.	1
Natural variantⁱVAR_000181	553	R → Q in CF. Corresponds to variant dbSNP:rs121909044EnsemblClinVar.	1
Natural variantⁱVAR_000182	558	L → S in CF. Corresponds to variant dbSNP:rs193922504EnsemblClinVar.	1
Natural variantⁱVAR_000183	559	A → T in CF; impaired maturation of glycan chains. 1 PublicationCorresponds to variant dbSNP:rs75549581EnsemblClinVar.	1
Natural variantⁱVAR_000184	560	R → K in CF. Corresponds to variant dbSNP:rs80055610EnsemblClinVar.	1
Natural variantⁱVAR_000185	560	R → S in CF. 1 PublicationCorresponds to variant dbSNP:rs397508267EnsemblClinVar.	1
Natural variantⁱVAR_000186	560	R → T in CF; impairs maturation and trafficking to the cell membrane; decrease in channel activity. 1 PublicationCorresponds to variant dbSNP:rs80055610EnsemblClinVar.	1
Natural variantⁱVAR_080307	561	A → E in CF; impairs maturation and trafficking to the cell membrane; decrease in channel activity. 1 PublicationCorresponds to variant dbSNP:rs121909047EnsemblClinVar.	1
Natural variantⁱVAR_000187	562	V → I in CBAVD and CF; unknown pathological significance; found in cis of the IVS8 TG11-T5 allele, which affects exon 9 splicing; no effect on protein maturation, trafficking to the cell membrane, nor on channel activity. 4 PublicationsCorresponds to variant dbSNP:rs1800097EnsemblClinVar.	1
Natural variantⁱVAR_000188	562	V → L in CF. 1 PublicationCorresponds to variant dbSNP:rs1800097EnsemblClinVar.	1
Natural variantⁱVAR_000189	563	Y → N in CF. Corresponds to variant dbSNP:rs121909006EnsemblClinVar.	1
Natural variantⁱVAR_000190	569	Y → C in CF. 1 PublicationCorresponds to variant dbSNP:rs397508277EnsemblClinVar.	1
Natural variantⁱVAR_000191	569	Y → D in CF. 1 PublicationCorresponds to variant dbSNP:rs397508276EnsemblClinVar.	1
Natural variantⁱVAR_000192	569	Y → H in CF. Corresponds to variant dbSNP:rs397508276EnsemblClinVar.	1
Natural variantⁱVAR_000193	571	L → S in CF. Corresponds to variant dbSNP:rs397508280EnsemblClinVar.	1
Natural variantⁱVAR_000194	572	D → N in CF; impaired maturation of glycan chains. 2 PublicationsCorresponds to variant dbSNP:rs397508282EnsemblClinVar.	1
Natural variantⁱVAR_000195	574	P → H in CF. Corresponds to variant dbSNP:rs121908758EnsemblClinVar.	1
Natural variantⁱVAR_000197	579	D → G in CF. 2 PublicationsCorresponds to variant dbSNP:rs397508288EnsemblClinVar.	1
Natural variantⁱVAR_000198	601	I → F in CF; impaired maturation of glycan chains. 1 PublicationCorresponds to variant dbSNP:rs397508306EnsemblClinVar.	1
Natural variantⁱVAR_000199	610	L → S in CF; impaired maturation of glycan chains. 1 PublicationCorresponds to variant dbSNP:rs397508311EnsemblClinVar.	1
Natural variantⁱVAR_000200	613	A → T in CF; impaired maturation of glycan chains. 1 PublicationCorresponds to variant dbSNP:rs201978662EnsemblClinVar.	1
Natural variantⁱVAR_000201	614	D → G in CF; impaired maturation of glycan chains. 1 PublicationCorresponds to variant dbSNP:rs201124247EnsemblClinVar.	1
Natural variantⁱVAR_000202	618	I → T in CF; impaired maturation of glycan chains. 1 PublicationCorresponds to variant dbSNP:rs139468767EnsemblClinVar.	1
Natural variantⁱVAR_000203	619	L → S in CF; impaired maturation of glycan chains. 2 PublicationsCorresponds to variant dbSNP:rs397508313EnsemblClinVar.	1
Natural variantⁱVAR_000204	620	H → P in CF; impaired maturation of glycan chains. 1 PublicationCorresponds to variant dbSNP:rs397508314EnsemblClinVar.	1
Natural variantⁱVAR_000205	620	H → Q in CF; strong decrease in bicarbonate transport; increase in chloride channel activity in vitro; no effect on glycan maturation. 1 PublicationCorresponds to variant dbSNP:rs397508315EnsemblClinVar.	1
Natural variantⁱVAR_000207	628	G → R in CF; impaired maturation of glycan chains. 2 PublicationsCorresponds to variant dbSNP:rs397508316EnsemblClinVar.	1
Natural variantⁱVAR_000208	633	L → P in CF; impaired maturation of glycan chains. 1 PublicationCorresponds to variant dbSNP:rs397508318EnsemblClinVar.	1
Natural variantⁱVAR_000209	648	D → V in CF; decrease in bicarbonate transport; no effect chloride channel activity. 1 PublicationCorresponds to variant dbSNP:rs121909033EnsemblClinVar.	1
Natural variantⁱVAR_000210	651	D → N in CF. Corresponds to variant dbSNP:rs780526529Ensembl.	1
Natural variantⁱVAR_000211	665	T → S in CF; no effect on glycan maturation and channel activity. 2 PublicationsCorresponds to variant dbSNP:rs1177201180Ensembl.	1
Natural variantⁱVAR_000213	693	F → L in CF; unknown pathological significance. 2 PublicationsCorresponds to variants dbSNP:rs145540754 and dbSNP:rs397508338EnsemblClinVarEnsembl.	1
Natural variantⁱVAR_080308	710 – 1480	Missing in CF. 1 PublicationAdd BLAST	771
Natural variantⁱVAR_000214	754	V → M in CF. Corresponds to variant dbSNP:rs150157202EnsemblClinVar.	1
Natural variantⁱVAR_000219	822	E → K in CF. Corresponds to variant dbSNP:rs397508378EnsemblClinVar.	1
Natural variantⁱVAR_080309	846 – 1480	Missing in CF. 1 PublicationAdd BLAST	635
Natural variantⁱVAR_000221	866	C → Y in CF. Corresponds to variant dbSNP:rs193922506EnsemblClinVar.	1
Natural variantⁱVAR_080310	890 – 1480	Missing in CF. 2 PublicationsAdd BLAST	591
Natural variantⁱVAR_000223	913	Y → C in CF. 1 PublicationCorresponds to variant dbSNP:rs121909008EnsemblClinVar.	1
Natural variantⁱVAR_000224	917	Y → C in CF. Corresponds to variant dbSNP:rs397508428EnsemblClinVar.	1
Natural variantⁱVAR_000225	949	H → Y in CF; decrease in bicarbonate transport; no effect on chloride channel activity. 2 PublicationsCorresponds to variant dbSNP:rs121909035EnsemblClinVar.	1
Natural variantⁱVAR_000226	952	M → I in CF and CBAVD; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs151048781EnsemblClinVar.	1
Natural variantⁱVAR_000227	997	L → F in CF and CBAVD; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1800111EnsemblClinVar.	1
Natural variantⁱVAR_000228	1005	I → R in CF. 1 PublicationCorresponds to variant dbSNP:rs397508479EnsemblClinVar.	1
Natural variantⁱVAR_000229	1006	A → E in CF. 2 PublicationsCorresponds to variant dbSNP:rs397508480EnsemblClinVar.	1
Natural variantⁱVAR_000230	1013	P → L in CF. 1 PublicationCorresponds to variant dbSNP:rs193922516EnsemblClinVar.	1
Natural variantⁱVAR_080314	1023 – 1024	Missing in CF; unknown pathological significance. 1 Publication	2
Natural variantⁱVAR_000231	1028	M → I in CF. 1 PublicationCorresponds to variant dbSNP:rs200553511EnsemblClinVar.	1
Natural variantⁱVAR_000232	1052	F → V in CF. 1 PublicationCorresponds to variant dbSNP:rs150212784EnsemblClinVar.	1
Natural variantⁱVAR_000233	1061	G → R in CF. 2 PublicationsCorresponds to variant dbSNP:rs142394380EnsemblClinVar.	1
Natural variantⁱVAR_080317	1063 – 1480	Missing in CF. 1 PublicationAdd BLAST	418
Natural variantⁱVAR_000234	1065	L → P in CF. 1 PublicationCorresponds to variant dbSNP:rs121909036EnsemblClinVar.	1
Natural variantⁱVAR_000235	1065	L → R in CF. 1 PublicationCorresponds to variant dbSNP:rs121909036EnsemblClinVar.	1
Natural variantⁱVAR_000236	1066	R → C in CF. 2 PublicationsCorresponds to variant dbSNP:rs78194216EnsemblClinVar.	1
Natural variantⁱVAR_000237	1066	R → H in CF. Corresponds to variant dbSNP:rs121909019EnsemblClinVar.	1
Natural variantⁱVAR_000238	1066	R → L in CF. 1 PublicationCorresponds to variant dbSNP:rs121909019EnsemblClinVar.	1
Natural variantⁱVAR_000239	1067	A → T in CF; loss of bicarbonate transport; no effect on protein maturation, subcellular location at the plasma membrane, nor on chloride channel activity. 1 PublicationCorresponds to variant dbSNP:rs121909020EnsemblClinVar.	1
Natural variantⁱVAR_000242	1070	R → P in CF. 1 PublicationCorresponds to variant dbSNP:rs78769542EnsemblClinVar.	1
Natural variantⁱVAR_000241	1070	R → Q in CF; decrease in bicarbonate transport; no effect on chloride channel activity. 2 PublicationsCorresponds to variant dbSNP:rs78769542EnsemblClinVar.	1
Natural variantⁱVAR_000243	1071	Q → P in CF. 1 PublicationCorresponds to variant dbSNP:rs121909037EnsemblClinVar.	1
Natural variantⁱVAR_000244	1072	P → L in CF.	1
Natural variantⁱVAR_000245	1077	L → P in CF. Corresponds to variant dbSNP:rs139304906EnsemblClinVar.	1
Natural variantⁱVAR_000246	1085	H → R in CF. 1 PublicationCorresponds to variant dbSNP:rs79635528EnsemblClinVar.	1
Natural variantⁱVAR_080319	1092 – 1480	Missing in CF. 1 PublicationAdd BLAST	389
Natural variantⁱVAR_000247	1098	W → R in CF. 1 PublicationCorresponds to variant dbSNP:rs397508531EnsemblClinVar.	1
Natural variantⁱVAR_000248	1101	M → K in CF. 1 PublicationCorresponds to variant dbSNP:rs36210737EnsemblClinVar.	1
Natural variantⁱVAR_011565	1101	M → R in CF. 1 PublicationCorresponds to variant dbSNP:rs36210737EnsemblClinVar.	1
Natural variantⁱVAR_000249	1137	M → V in CF; decreases channel activity; no visible effect on protein maturation. 1 PublicationCorresponds to variant dbSNP:rs397508553EnsemblClinVar.	1
Natural variantⁱVAR_000250	1140	Missing in CF; abolishes channel activity; no visible effect on protein maturation. 2 Publications	1
Natural variantⁱVAR_000251	1152	D → H in CF and CBAVD; decreases channel activity; no visible effect on protein maturation. 2 PublicationsCorresponds to variant dbSNP:rs75541969EnsemblClinVar.	1
Natural variantⁱVAR_080321	1162 – 1480	Missing in CF. 1 PublicationAdd BLAST	319
Natural variantⁱVAR_080322	1200	K → E in CF; unknown pathological significance. 1 Publication	1
Natural variantⁱVAR_080323	1204 – 1480	Missing in CF. 1 PublicationAdd BLAST	277
Natural variantⁱVAR_000254	1234	I → V in CF. Corresponds to variant dbSNP:rs75389940EnsemblClinVar.	1
Natural variantⁱVAR_000255	1235	S → R in CF. Corresponds to variant dbSNP:rs34911792EnsemblClinVar.	1
Natural variantⁱVAR_000256	1244	G → E in CF; loss of bicarbonate transport; no effect on protein maturation, subcellular location at the plasma membrane, nor on chloride channel activity. 1 PublicationCorresponds to variant dbSNP:rs267606723EnsemblClinVar.	1
Natural variantⁱVAR_000257	1249	G → E in CF. 1 PublicationCorresponds to variant dbSNP:rs121909040EnsemblClinVar.	1
Natural variantⁱVAR_000258	1251	S → N in CF. Corresponds to variant dbSNP:rs74503330EnsemblClinVar.	1
Natural variantⁱVAR_000259	1255	S → P in CF; loss of bicarbonate transport; no effect on protein maturation, subcellular location at the plasma membrane, nor on chloride channel activity. 2 PublicationsCorresponds to variant dbSNP:rs121909041EnsemblClinVar.	1
Natural variantⁱVAR_000260	1270	D → N in CF and CBAVD. 1 PublicationCorresponds to variant dbSNP:rs11971167EnsemblClinVar.	1
Natural variantⁱVAR_080324	1282 – 1480	Missing in CF and CBAVD. 2 PublicationsAdd BLAST	199
Natural variantⁱVAR_000261	1282	W → R in CF. Corresponds to variant dbSNP:rs397508616EnsemblClinVar.	1
Natural variantⁱVAR_000262	1283	R → M in CF. 1 PublicationCorresponds to variant dbSNP:rs77902683EnsemblClinVar.	1
Natural variantⁱVAR_000263	1286	F → S in CF. Corresponds to variant dbSNP:rs121909028EnsemblClinVar.	1
Natural variantⁱVAR_000264	1291	Q → H in CF. 1 PublicationCorresponds to variant dbSNP:rs121909015EnsemblClinVar.	1
Natural variantⁱVAR_000265	1291	Q → R in CF. 1 PublicationCorresponds to variant dbSNP:rs397508621EnsemblClinVar.	1
Natural variantⁱVAR_000266	1303	N → H in CF. Corresponds to variant dbSNP:rs121909042EnsemblClinVar.	1
Natural variantⁱVAR_000267	1303	N → K in CF; impaired maturation of glycan chains; has low in vitro channel activity at low temperature. 5 PublicationsCorresponds to variant dbSNP:rs80034486EnsemblClinVar.	1
Natural variantⁱVAR_000268	1349	G → D in CF; loss of bicarbonate transport; no effect on protein maturation, subcellular location at the plasma membrane, nor on chloride channel activity. 2 PublicationsCorresponds to variant dbSNP:rs193922525EnsemblClinVar.	1
Natural variantⁱVAR_000270	1397	V → E in CF. 1 PublicationCorresponds to variant dbSNP:rs397508691EnsemblClinVar.	1

Congenital bilateral absence of the vas deferens (CBAVD)7 Publications

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

Disease descriptionImportant cause of sterility in men and could represent an incomplete form of cystic fibrosis, as the majority of men suffering from cystic fibrosis lack the vas deferens.

UniProtKB - P13569 (CFTR_HUMAN)

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Cystic fibrosis transmembrane conductance regulator

CFTR

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