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

ENSG00000001626 ∙ NCBI:1080 ∙ OMIM:602421 ∙ HGNC:1884 ∙ Uniprot:P13569 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cystic fibrosis (Definitive), mode of inheritance: AR
• cystic fibrosis (Supportive), mode of inheritance: AR
• congenital bilateral absence of vas deferens (Supportive), 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: CGD

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 ClinVar and linked to the CFTR gene.

• Cystic_fibrosis (4948 variants)
• CFTR-related_disorder (1249 variants)
• not_provided (980 variants)
• not_specified (917 variants)
• Bronchiectasis_with_or_without_elevated_sweat_chloride_1 (609 variants)
• Congenital_bilateral_aplasia_of_vas_deferens_from_CFTR_mutation (463 variants)
• Hereditary_pancreatitis (413 variants)
• ivacaftor_response_-_Efficacy (32 variants)
• Obstructive_azoospermia (16 variants)
• Respiratory_ciliopathies_including_non-CF_bronchiectasis (6 variants)
• Infertility_disorder (5 variants)
• See_cases (3 variants)
• Lung_disease,_non-specific (3 variants)
• Spermatogenic_failure,_Y-linked,_2 (2 variants)
• Inborn_genetic_diseases (2 variants)
• Chronic_pancreatitis (2 variants)
• . (2 variants)
• Chronic_sinusitis (2 variants)
• Megacolon (2 variants)
• Pseudomonas_aeruginosa,_susceptibility_to_chronic_infection_by,_in_cystic_fibrosis (2 variants)
• ivacaftor_/_lumacaftor_response_-_Efficacy (1 variants)
• Schizophrenia (1 variants)
• Von_Hippel-Lindau_syndrome (1 variants)
• Abnormality_of_metabolism/homeostasis (1 variants)
• Bronchiectasis_with_or_without_elevated_sweat_chloride_1,_modifier_of (1 variants)
• Nephronophthisis_14 (1 variants)
• Hereditary_nonpolyposis_colon_cancer (1 variants)
• Breast_neoplasm (1 variants)
• Sweat_chloride_elevation_without_cystic_fibrosis (1 variants)
• Pancreatitis (1 variants)
• Male_infertility (1 variants)
• Fetal_cystic_hygroma (1 variants)
• Duodenal_stenosis (1 variants)
• ivacaftor_/_tezacaftor_response_-_Efficacy (1 variants)
• Recurrent_pancreatitis (1 variants)
• Congenital_bilateral_absence_of_vas_deferens (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. These statistics are base on transcript: NM_000000492.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	12	8	58	965	6	1049
missense	164	264	1989	39	3	2459
nonsense	216	82	14			312
start loss	6		1			7
frameshift	368	155	31			554
splice donor/acceptor (+/-2bp)	98	94	15			207
Total	864	603	2108	1004	9

Highest pathogenic variant AF is 0.0119312545

GnomAD

Source: gnomAD

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: dbNSFP

• 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