CFTR
CF transmembrane conductance regulator, the group of ATP binding cassette subfamily C|Chloride channels, ATP-gated CFTR
Basic information
Region (hg38): 7:117287120-117715971
Previous symbols: [ "CF", "ABCC7" ]
Links
Phenotypes
GenCC
Source:
- cystic fibrosis (Supportive), mode of inheritance: AR
- congenital bilateral absence of vas deferens (Supportive), mode of inheritance: AR
- cystic fibrosis (Definitive), mode of inheritance: AR
- cystic fibrosis (Strong), mode of inheritance: AR
- hereditary chronic pancreatitis (Limited), mode of inheritance: AD
- cystic fibrosis (Definitive), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Cystic fibrosis | AR | Allergy/Immunology/Infectious; Endocrine; Gastrointestinal; Pulmonary | Early and aggressive multisystem management of pulmonary (with attention to infectious risks), pancreatic, and other manifestations can reduce morbidity and mortality; In the instance of specific variants, targeted therapy (eg, ivacaftor) has been described as beneficial | Allergy/Immunology/Infectious; Endocrine; Gastrointestinal; Genitourinary; Pulmonary | 5657013; 2296270; 1870650; 1284639; 1359500; 7678316; 7680769; 7739684; 7529962; 7539210; 9003498; 9395429; 9113931; 9150159; 9550361; 18685558; 9725921; 11134427; 12768409; 15948195; 17018651; 16778595; 17202412; 7413420; 18685558; 21083385; 21184098; 22047557; 22383668; 22942289; 23590265; 23616732; 23616952; 23757359; 23952705; 24004658; 24039402 |
ClinVar
This is a list of variants' phenotypes submitted to
- Cystic fibrosis (727 variants)
- CFTR-related disorder (287 variants)
- Bronchiectasis with or without elevated sweat chloride 1 (231 variants)
- not provided (188 variants)
- not specified (73 variants)
- Cystic fibrosis;Congenital bilateral aplasia of vas deferens from CFTR mutation (70 variants)
- Congenital bilateral aplasia of vas deferens from CFTR mutation;Cystic fibrosis (46 variants)
- Cystic fibrosis;CFTR-related disorder (29 variants)
- Congenital bilateral aplasia of vas deferens from CFTR mutation;Hereditary pancreatitis;Cystic fibrosis;Bronchiectasis with or without elevated sweat chloride 1 (26 variants)
- Hereditary pancreatitis (24 variants)
- CFTR-related disorder;Cystic fibrosis (23 variants)
- Bronchiectasis with or without elevated sweat chloride 1;Hereditary pancreatitis;Cystic fibrosis;Congenital bilateral aplasia of vas deferens from CFTR mutation (14 variants)
- Cystic fibrosis;Hereditary pancreatitis;Bronchiectasis with or without elevated sweat chloride 1;Congenital bilateral aplasia of vas deferens from CFTR mutation (7 variants)
- Obstructive azoospermia (6 variants)
- Congenital bilateral aplasia of vas deferens from CFTR mutation (5 variants)
- Bronchiectasis with or without elevated sweat chloride 1;Cystic fibrosis;Hereditary pancreatitis;Congenital bilateral aplasia of vas deferens from CFTR mutation (3 variants)
- ivacaftor response - Efficacy (3 variants)
- Cystic fibrosis;Congenital bilateral aplasia of vas deferens from CFTR mutation;Bronchiectasis with or without elevated sweat chloride 1;Hereditary pancreatitis (3 variants)
- Inborn genetic diseases (2 variants)
- See cases (2 variants)
- Cystic fibrosis;Bronchiectasis with or without elevated sweat chloride 1;Congenital bilateral aplasia of vas deferens from CFTR mutation;Hereditary pancreatitis (2 variants)
- Hereditary pancreatitis;Cystic fibrosis (2 variants)
- Bronchiectasis with or without elevated sweat chloride 1;Hereditary pancreatitis;Congenital bilateral aplasia of vas deferens from CFTR mutation;Cystic fibrosis (2 variants)
- Cystic fibrosis;Bronchiectasis with or without elevated sweat chloride 1;Hereditary pancreatitis;Congenital bilateral aplasia of vas deferens from CFTR mutation (2 variants)
- Hereditary pancreatitis;Cystic fibrosis;Congenital bilateral aplasia of vas deferens from CFTR mutation;Bronchiectasis with or without elevated sweat chloride 1 (1 variants)
- Duodenal stenosis (1 variants)
- Bronchiectasis with or without elevated sweat chloride 1, modifier of (1 variants)
- ivacaftor / lumacaftor response - Efficacy (1 variants)
- Bronchiectasis with or without elevated sweat chloride 1;Congenital bilateral aplasia of vas deferens from CFTR mutation;Cystic fibrosis;Hereditary pancreatitis (1 variants)
- Multiple acyl-CoA dehydrogenase deficiency (1 variants)
- Congenital bilateral aplasia of vas deferens from CFTR mutation;Bronchiectasis with or without elevated sweat chloride 1;Hereditary pancreatitis;Cystic fibrosis (1 variants)
- Abnormality of metabolism/homeostasis (1 variants)
- Spermatogenic failure, Y-linked, 2 (1 variants)
- ivacaftor / tezacaftor response - Efficacy (1 variants)
- Recurrent pancreatitis (1 variants)
- Pseudomonas aeruginosa, susceptibility to chronic infection by, in cystic fibrosis (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CFTR gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 10 | 756 | 767 | |||
| missense | 121 | 74 | 1439 | 1643 | ||
| nonsense | 191 | 83 | 275 | |||
| start loss | 6 | |||||
| frameshift | 304 | 142 | 447 | |||
| inframe indel | 35 | 52 | ||||
| splice donor/acceptor (+/-2bp) | 81 | 69 | 152 | |||
| splice region | 19 | 6 | 78 | 107 | 4 | 214 |
| non coding | 12 | 182 | 374 | 62 | 634 | |
| Total | 722 | 382 | 1670 | 1139 | 63 |
Highest pathogenic variant AF is 0.00788
Variants in CFTR
This is a list of pathogenic ClinVar variants found in the CFTR region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 7-117297673-C-T | Benign (Jun 13, 2018) | |||
| 7-117297734-A-G | not specified | Uncertain significance (Nov 03, 2022) | ||
| 7-117297776-G-A | not specified | Uncertain significance (Feb 28, 2024) | ||
| 7-117297862-G-T | not specified | Uncertain significance (Apr 30, 2024) | ||
| 7-117315142-C-A | not specified | Uncertain significance (Oct 25, 2023) | ||
| 7-117315153-C-T | not specified | Uncertain significance (Jul 12, 2022) | ||
| 7-117315241-T-C | not specified | Uncertain significance (Aug 17, 2021) | ||
| 7-117315342-C-T | not specified | Uncertain significance (Dec 19, 2022) | ||
| 7-117320668-G-A | not specified | Uncertain significance (Jun 02, 2024) | ||
| 7-117320674-C-G | not specified | Uncertain significance (Aug 12, 2022) | ||
| 7-117320677-T-C | not specified | Uncertain significance (Jun 05, 2024) | ||
| 7-117320690-G-A | not specified | Uncertain significance (May 30, 2023) | ||
| 7-117320716-A-G | not specified | Uncertain significance (Jun 07, 2024) | ||
| 7-117320789-T-C | not specified | Uncertain significance (Oct 13, 2023) | ||
| 7-117363735-C-T | not specified | Uncertain significance (Apr 26, 2024) | ||
| 7-117363736-G-A | not specified | Uncertain significance (May 25, 2022) | ||
| 7-117363748-A-G | not specified | Likely benign (Feb 27, 2024) | ||
| 7-117368625-A-C | not specified | Uncertain significance (Aug 10, 2021) | ||
| 7-117368682-T-C | not specified | Uncertain significance (Nov 30, 2021) | ||
| 7-117368717-A-G | not specified | Likely benign (Jul 12, 2023) | ||
| 7-117379945-C-T | not specified | Uncertain significance (Mar 22, 2022) | ||
| 7-117381034-T-C | not specified | Uncertain significance (May 01, 2022) | ||
| 7-117382088-T-C | not specified | Uncertain significance (Dec 27, 2023) | ||
| 7-117383044-C-T | not specified | Uncertain significance (Jun 06, 2023) | ||
| 7-117383071-C-G | not specified | Uncertain significance (Jan 03, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| CFTR | protein_coding | protein_coding | ENST00000003084 | 27 | 250188 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 2.17e-58 | 1.72e-10 | 125053 | 0 | 695 | 125748 | 0.00277 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -3.14 | 996 | 753 | 1.32 | 0.0000380 | 9674 |
| Missense in Polyphen | 180 | 116.88 | 1.5401 | 1501 | ||
| Synonymous | 0.774 | 256 | 272 | 0.940 | 0.0000142 | 2819 |
| Loss of Function | -0.734 | 84 | 77.0 | 1.09 | 0.00000404 | 938 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00604 | 0.00603 |
| Ashkenazi Jewish | 0.0113 | 0.0114 |
| East Asian | 0.000490 | 0.000489 |
| Finnish | 0.00172 | 0.00171 |
| European (Non-Finnish) | 0.00271 | 0.00269 |
| Middle Eastern | 0.000490 | 0.000489 |
| South Asian | 0.00242 | 0.00242 |
| Other | 0.00164 | 0.00163 |
dbNSFP
Source:
- Function
- FUNCTION: 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). {ECO:0000269|PubMed:10792060, ECO:0000269|PubMed:11524016, ECO:0000269|PubMed:11707463, ECO:0000269|PubMed:12403779, ECO:0000269|PubMed:12519745, ECO:0000269|PubMed:12529365, ECO:0000269|PubMed:12588899, ECO:0000269|PubMed:14668433, ECO:0000269|PubMed:15010471, ECO:0000269|PubMed:16645176, ECO:0000269|PubMed:17036051, ECO:0000269|PubMed:1712898, ECO:0000269|PubMed:17182731, ECO:0000269|PubMed:19019741, ECO:0000269|PubMed:19398555, ECO:0000269|PubMed:19621064, ECO:0000269|PubMed:22178883, ECO:0000269|PubMed:25330774, ECO:0000269|PubMed:26627831, ECO:0000269|PubMed:26823428, ECO:0000269|PubMed:26846474, ECO:0000269|PubMed:27714810, ECO:0000269|PubMed:27941075, ECO:0000269|PubMed:28087700, ECO:0000269|PubMed:8910473, ECO:0000269|PubMed:9804160, ECO:0000305|PubMed:19923167}.;
- Disease
- DISEASE: Cystic fibrosis (CF) [MIM:219700]: A 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. {ECO:0000269|PubMed:10094564, ECO:0000269|PubMed:11242048, ECO:0000269|PubMed:12167682, ECO:0000269|PubMed:12394343, ECO:0000269|PubMed:12529365, ECO:0000269|PubMed:1284466, ECO:0000269|PubMed:1284468, ECO:0000269|PubMed:1284529, ECO:0000269|PubMed:1284530, ECO:0000269|PubMed:1284548, ECO:0000269|PubMed:1379210, ECO:0000269|PubMed:15528182, ECO:0000269|PubMed:15716351, ECO:0000269|PubMed:16822950, ECO:0000269|PubMed:1695717, ECO:0000269|PubMed:1699669, ECO:0000269|PubMed:17098864, ECO:0000269|PubMed:1710600, ECO:0000269|PubMed:1712898, ECO:0000269|PubMed:17182731, ECO:0000269|PubMed:20008117, ECO:0000269|PubMed:20150177, ECO:0000269|PubMed:20691141, ECO:0000269|PubMed:2236053, ECO:0000269|PubMed:25330774, ECO:0000269|PubMed:26846474, ECO:0000269|PubMed:28001373, ECO:0000269|PubMed:28087700, ECO:0000269|PubMed:7504969, ECO:0000269|PubMed:7505694, ECO:0000269|PubMed:7513296, ECO:0000269|PubMed:7517264, ECO:0000269|PubMed:7520022, ECO:0000269|PubMed:7522211, ECO:0000269|PubMed:7524909, ECO:0000269|PubMed:7524913, ECO:0000269|PubMed:7525450, ECO:0000269|PubMed:7537150, ECO:0000269|PubMed:7541273, ECO:0000269|PubMed:7541510, ECO:0000269|PubMed:7543567, ECO:0000269|PubMed:7544319, ECO:0000269|PubMed:7581407, ECO:0000269|PubMed:7606851, ECO:0000269|PubMed:7680525, ECO:0000269|PubMed:7683628, ECO:0000269|PubMed:7683954, ECO:0000269|PubMed:8081395, ECO:0000269|PubMed:8406518, ECO:0000269|PubMed:8522333, ECO:0000269|PubMed:8723693, ECO:0000269|PubMed:8723695, ECO:0000269|PubMed:8800923, ECO:0000269|PubMed:8829633, ECO:0000269|PubMed:8910473, ECO:0000269|PubMed:8956039, ECO:0000269|PubMed:9101301, ECO:0000269|PubMed:9222768, ECO:0000269|PubMed:9375855, ECO:0000269|PubMed:9401006, ECO:0000269|PubMed:9443874, ECO:0000269|PubMed:9452048, ECO:0000269|PubMed:9452054, ECO:0000269|PubMed:9452073, ECO:0000269|PubMed:9482579, ECO:0000269|PubMed:9521595, ECO:0000269|PubMed:9554753, ECO:0000269|PubMed:9736778, ECO:0000269|PubMed:9804160, ECO:0000269|PubMed:9921909}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Congenital bilateral absence of the vas deferens (CBAVD) [MIM:277180]: Important 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. {ECO:0000269|PubMed:10651488, ECO:0000269|PubMed:17329263, ECO:0000269|PubMed:7529962, ECO:0000269|PubMed:7539342, ECO:0000269|PubMed:9067761, ECO:0000269|PubMed:9736778, ECO:0000269|Ref.113}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Tight junction - Homo sapiens (human);Bile secretion - Homo sapiens (human);Gastric acid secretion - Homo sapiens (human);AMPK signaling pathway - Homo sapiens (human);ABC transporters - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Vibrio cholerae infection - Homo sapiens (human);Pancreatic secretion - Homo sapiens (human);Disorders of transmembrane transporters;Disease;Signal Transduction;Defective CFTR causes cystic fibrosis;Vesicle-mediated transport;cystic fibrosis transmembrane conductance regulator (cftr) and beta 2 adrenergic receptor (b2ar) pathway;Membrane Trafficking;Post-translational protein modification;Metabolism of proteins;Transport of small molecules;RHO GTPases regulate CFTR trafficking;RHO GTPase Effectors;Signaling by Rho GTPases;Clathrin-mediated endocytosis;ABC-family proteins mediated transport;Ub-specific processing proteases;Deubiquitination;Cargo recognition for clathrin-mediated endocytosis;ABC transporter disorders
(Consensus)
Recessive Scores
- pRec
- 0.877
Intolerance Scores
- loftool
- 0.0235
- rvis_EVS
- -0.51
- rvis_percentile_EVS
- 21.73
Haploinsufficiency Scores
- pHI
- 0.766
- hipred
- Y
- hipred_score
- 0.619
- ghis
- 0.430
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.695
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Cftr
- Phenotype
- homeostasis/metabolism phenotype; craniofacial phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; liver/biliary system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; digestive/alimentary phenotype; vision/eye phenotype; hematopoietic system phenotype; reproductive system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span);
Zebrafish Information Network
- Gene name
- cftr
- Affected structure
- secondary islet
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- cholesterol biosynthetic process;vesicle docking involved in exocytosis;bicarbonate transport;protein deubiquitination;cholesterol transport;response to endoplasmic reticulum stress;transepithelial water transport;positive regulation of insulin secretion involved in cellular response to glucose stimulus;positive regulation of exocytosis;sperm capacitation;multicellular organismal water homeostasis;intracellular pH elevation;transmembrane transport;membrane hyperpolarization;membrane organization;cellular response to cAMP;ATP hydrolysis coupled anion transmembrane transport;positive regulation of cyclic nucleotide-gated ion channel activity;chloride transmembrane transport;positive regulation of voltage-gated chloride channel activity;cellular response to forskolin
- Cellular component
- nucleus;cytoplasm;lysosomal membrane;early endosome;endoplasmic reticulum membrane;cytosol;plasma membrane;integral component of plasma membrane;cell surface;endosome membrane;membrane;integral component of membrane;apical plasma membrane;Golgi-associated vesicle membrane;clathrin-coated vesicle membrane;early endosome membrane;protein-containing complex;chloride channel complex;recycling endosome;recycling endosome membrane
- Molecular function
- chloride channel activity;intracellularly ATP-gated chloride channel activity;protein binding;ATP binding;bicarbonate transmembrane transporter activity;chloride transmembrane transporter activity;ATPase activity;chloride channel regulator activity;chloride channel inhibitor activity;enzyme binding;PDZ domain binding;ATPase activity, coupled to transmembrane movement of substances;ATPase-coupled anion transmembrane transporter activity;chaperone binding;Sec61 translocon complex binding