UniProtKB - P13569 (CFTR_HUMAN)
Protein
Cystic fibrosis transmembrane conductance regulator
Gene
CFTR
Organism
Homo sapiens (Human)
Status
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 HCO3-; 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 + H(2)O + closed Cl(-) channel = ADP + phosphate + open Cl(-) channel.4 Publications EC:5.6.1.6
Sites
| Feature key | Position(s) | DescriptionActions | Graphical view | 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
- ATPase-coupled transmembrane transporter activity Source: GO_Central
- ATP binding Source: ProtInc
- bicarbonate transmembrane transporter activity Source: UniProtKB
- chaperone binding Source: ARUK-UCL
- chloride channel activity Source: UniProtKB
- chloride channel inhibitor activity Source: UniProtKB
- chloride channel regulator activity Source: Reactome
- chloride transmembrane transporter activity Source: UniProtKB
- enzyme binding Source: UniProtKB
- intracellularly ATP-gated chloride channel activity Source: UniProtKB
- isomerase activity Source: UniProtKB-KW
- PDZ domain binding Source: UniProtKB
- Sec61 translocon complex binding Source: UniProtKB
GO - Biological processi
- bicarbonate transport Source: UniProtKB
- cellular response to cAMP Source: UniProtKB
- cellular response to forskolin Source: UniProtKB
- chloride transmembrane transport Source: UniProtKB
- 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
- positive regulation of cyclic nucleotide-gated ion channel activity Source: UniProtKB
- positive regulation of exocytosis Source: UniProtKB
- positive regulation of insulin secretion involved in cellular response to glucose stimulus Source: UniProtKB
- positive regulation of voltage-gated chloride channel activity Source: UniProtKB
- protein deubiquitination Source: Reactome
- response to endoplasmic reticulum stress Source: UniProtKB
- sperm capacitation Source: UniProtKB
- transepithelial water transport Source: UniProtKB
- transmembrane transport Source: GO_Central
- vesicle docking involved in exocytosis Source: Ensembl
Keywordsi
| Molecular function | Chloride channel, Ion channel, Isomerase |
| 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 |
| PathwayCommonsi | P13569 |
| 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 R-HSA-9613829, Chaperone Mediated Autophagy R-HSA-9615710, Late endosomal microautophagy R-HSA-9646399, Aggrephagy |
| 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 regulatorShort name: CFTR Alternative name(s): ATP-binding cassette sub-family C member 7 Channel conductance-controlling ATPase (EC:5.6.1.64 Publications) cAMP-dependent chloride channel |
| Gene namesi | Name:CFTR Synonyms:ABCC7 |
| Organismi | Homo sapiens (Human) |
| Taxonomic identifieri | 9606 [NCBI] |
| Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
| Proteomesi |
|
Organism-specific databases
| HGNCi | HGNC:1884, CFTR |
| MIMi | 602421, gene |
| neXtProti | NX_P13569 |
| VEuPathDBi | HostDB:ENSG00000001626.14 |
Subcellular locationi
Plasma membrane
- Apical cell membrane 11 Publications; Multi-pass membrane protein 1 Publication
- Cell membrane 1 Publication19 Publications; Multi-pass membrane protein 1 Publication
Endoplasmic reticulum
- Endoplasmic reticulum membrane 2 Publications; Multi-pass membrane protein 1 Publication
Nucleus
- Nucleus By similarity
Endosome
- Early endosome membrane 2 Publications; Multi-pass membrane protein 1 Publication
- Recycling endosome membrane 1 Publication; Multi-pass membrane protein 1 Publication
Note: The channel is internalized from the cell surface into an endosomal recycling compartment, from where it is recycled to the cell membrane (PubMed:17462998, PubMed:19398555, PubMed:20008117). In the oviduct and bronchus, detected on the apical side of epithelial cells, but not associated with cilia (PubMed:22207244). In Sertoli cells, a processed product is detected in the nucleus (By similarity). ER stress induces GORASP2-mediated unconventional (ER/Golgi-independent) trafficking of core-glycosylated CFTR to cell membrane (PubMed:21884936).By similarity1 Publication4 Publications
Cytosol
- cytosol Source: UniProtKB
Endoplasmic reticulum
- endoplasmic reticulum membrane Source: UniProtKB
Endosome
- early endosome Source: UniProtKB
- early endosome membrane Source: UniProtKB-SubCell
- endosome membrane Source: Reactome
- recycling endosome Source: UniProtKB
- recycling endosome membrane Source: UniProtKB-SubCell
Lysosome
- lysosomal membrane Source: Reactome
Nucleus
- nucleus Source: UniProtKB
Plasma Membrane
- apical plasma membrane Source: UniProtKB
- integral component of plasma membrane Source: UniProtKB
- plasma membrane Source: UniProtKB
Other locations
- cell surface Source: UniProtKB
- chloride channel complex Source: UniProtKB-KW
- clathrin-coated vesicle membrane Source: Reactome
- cytoplasm Source: UniProtKB
- Golgi-associated vesicle membrane Source: Reactome
- integral component of membrane Source: UniProtKB
- membrane Source: GO_Central
- protein-containing complex Source: UniProtKB
Topology
| Feature key | Position(s) | DescriptionActions | Graphical view | 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, NucleusPathology & Biotechi
Involvement in diseasei
Cystic fibrosis (CF)73 Publications
The disease is caused by variants affecting the gene represented in this entry. There is some evidence that the functional defect caused by the most common variant Phe-508 DEL can be corrected by the binding to the snake phospholipase A2 crotoxin basic subunit CB. This toxin both disrupts the Phe-508 DEL-cytokeratin 8 complex, allowing for the escape from degradation, and increases the chloride channel current (PubMed:27241308).1 Publication
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.
Related information in OMIM| Feature key | Position(s) | DescriptionActions | Graphical view | 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:rs201958172Ensembl. | 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; unknown pathological significance. 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; binds to the cytokeratin-8 and through this binding is primed for the degradation pathway that ends in the proteasome, thus impairing trafficking; impairs maturation and trafficking to the cell membrane; impairs recycling to the cell membrane after endocytosis. 19 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:rs780526529EnsemblClinVar. | 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:rs397508553Ensembl. | 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 Publications |