CFTR Gene Complete Identifier and Functional Mapping Reference
Provide a comprehensive cross-database identifier and functional mapping reference for human CFTR — a definitive lookup resource covering: ### Section 1: Gene identifiers For human gene CFTR, list ALL gene-level database identifiers. Required: - HGNC ID and approved symbol - Ensembl gene ID (ENSG...) - NCBI Entrez Gene ID - OMIM gene/locus ID - Genomic location: chromosome, start position, end position, strand (GRCh38) ### Section 2: Transcript identifiers For human gene CFTR, list ALL transcript-level identifiers. Required: - Ensembl transcripts: ALL ENST IDs with biotype. Total count. - RefSeq transcripts: ALL NM_ mRNA accessions. Mark which is MANE Select. - CCDS IDs. - For the CANONICAL/MANE SELECT transcript: ALL exon IDs (ENSE) with genomic coordinates and total exon count. ### Section 3: Protein identifiers For human gene CFTR protein product(s), list ALL protein-level identifiers. Required: - UniProt accessions: ALL entries (reviewed and unreviewed). Mark the canonical reviewed entry. - RefSeq protein: ALL NP_ accessions. - Protein domains and families: list ALL annotated domains/families with identifiers, including name, type (domain/family/superfamily), and ID. - Antibody availability: known antibody resources for the protein. ### Section 4: Structure For human gene CFTR protein, list ALL structural data. Required: - Experimental structures: ALL PDB IDs. For each: experimental method (X-ray/NMR/Cryo-EM) and resolution. Total count. - Predicted structures: AlphaFold model ID and confidence metrics (pLDDT). ### Section 5: Cross-species orthologs For human gene CFTR, list orthologous genes in key model organisms. Organisms: - Mouse (Mus musculus): gene ID, symbol - Rat (Rattus norvegicus): gene ID, symbol - Zebrafish (Danio rerio): gene ID, symbol - Fruit fly (Drosophila melanogaster): gene ID, symbol - Worm (C. elegans): gene ID, symbol - Yeast (S. cerevisiae): gene ID, symbol ### Section 6: Clinical variants & AI predictions For human gene CFTR, summarize clinical variants and AI predictions. Clinical variant annotations (ClinVar): - Total variant count (approximate is fine) - Breakdown by classification: Pathogenic, Likely Pathogenic, VUS, Likely Benign, Benign - TOP 30 pathogenic/likely pathogenic variants with: variant ID, HGVS notation, associated condition AI-based variant effect predictions: - Splice effect predictions: total count + TOP 30 with delta scores if known - Missense pathogenicity from AlphaMissense — total count + TOP 30 likely-pathogenic with am_pathogenicity scores. ### Section 7: Pathways & Gene Ontology For human gene CFTR, list biological pathways and Gene Ontology annotations. Pathway membership: - ALL biological pathways this gene participates in, with pathway IDs and names - Total pathway count Gene Ontology: - Biological Process: count and TOP 20 terms with GO IDs - Molecular Function: count and TOP 20 terms with GO IDs - Cellular Component: count and TOP 20 terms with GO IDs ### Section 8: Protein interactions & networks For human gene CFTR protein, summarize protein interactions and networks. Protein-protein interactions (STRING, IntAct, BioGRID, etc.): - Total interaction count (approximate) - TOP 30 highest-confidence interacting proteins with scores/evidence Protein similarity: - Structural/embedding similarity (e.g. Foldseek, ESM): TOP 20 similar proteins with scores - Sequence homology: TOP 20 homologous proteins with identity/similarity ### Section 9: Transcription factor regulatory data For human gene CFTR, summarize transcription factor regulatory data. If CFTR is a transcription factor: - Downstream targets: total count + TOP 30 with regulation type (activates/represses) and evidence - DNA binding motifs from JASPAR — all known motif IDs and motif family classification. Regardless: - Upstream regulators: TFs that regulate CFTR — names with evidence type (ChIP-seq / predicted / experimentally validated) If CFTR is not a transcription factor, say so briefly and skip the downstream/motif sections. ### Section 10: Drug & pharmacology data For human gene CFTR protein as a drug target, summarize pharmacology data. If CFTR is a known drug target: - Targeting molecules: total count in ChEMBL/DrugBank + TOP 30 by development phase (molecule ID, name, mechanism, highest phase) - Clinical trials: TOP 20 involving drugs targeting this gene — trial ID, phase, status, intervention - Pharmacogenomics: known drug-gene interactions affecting drug response + dosing guidelines if any If CFTR is not currently a drug target, say so briefly. ### Section 11: Expression profiles For human gene CFTR, summarize expression profiles. Tissue expression (GTEx, HPA, Bgee, etc.): - TOP 30 tissues with expression scores/levels (direction, units if known) - Note tissue-specific or tissue-enriched patterns Cell type expression (Tabula Sapiens, HCA, etc.): - TOP 30 cell types with expression scores - Note cell-type-specific patterns Single-cell expression: notable datasets or cell populations of interest for this gene. ### Section 12: Disease associations For human gene CFTR, summarize disease associations. Mendelian / monogenic disease: - Diseases caused by mutations in CFTR: disease name, disease ID (OMIM/Orphanet/Mondo), inheritance pattern, evidence level - Include all directly linked conditions Phenotype associations: - Clinical phenotypes associated with the gene (HPO terms where known) - TOP 30 phenotype terms with HPO IDs Complex-disease / GWAS: - Traits and diseases significantly associated via GWAS: trait name, variant, effect size, study where known - TOP 30 GWAS associations
Executive summary
CFTR (cystic fibrosis transmembrane conductance regulator, chromosome 7) encodes an ATP-gated chloride channel and ABC-family transporter that is the sole causal gene for cystic fibrosis, an autosomal recessive disease affecting lung, pancreas, intestine, and reproductive tissues. Its clinical importance is underscored by ~5,919 ClinVar variants, of which over 200 are classified pathogenic, and by expression data showing highest activity in pancreas (Bgee score 99.02), gallbladder, and colonic epithelium, consistent with its role in epithelial fluid and electrolyte transport. The protein has 58 experimental PDB structures and interacts with key chaperones (HSP90A/B, HSPA family) and PDZ scaffold proteins (NHERF1, GOPC) that govern its folding, trafficking, and membrane localization. CFTR is one of the most therapeutically tractable rare-disease targets: four combination regimens have received FDA approval — Orkambi (2015), Symkevi (2018), Trikafta (2019), and Alyftrek (2024) — with ivacaftor alone spanning 72 clinical trials, and mutation-specific pharmacogenomics guiding treatment selection for gating (G551D → ivacaftor) and processing defects (F508del → corrector/potentiator combinations).
CFTR — Reference
Cross-database identifier and functional mapping reference for CFTR.
Gene identifiers
CFTR (CF transmembrane conductance regulator)
- HGNC ID: HGNC:1884
- Approved symbol: CFTR
- Ensembl gene ID: ENSG00000001626
- NCBI Entrez Gene ID: 1080
- OMIM locus ID: 602421
- Genomic location (GRCh38):
- Chromosome: 7
- Start position: 117,287,120
- End position: 117,715,971
- Strand: +
Transcript identifiers
Ensembl Transcripts
| ENST ID | Biotype | Count |
|---|---|---|
| ENST00000003084 | protein_coding | 1 |
| ENST00000426809 | protein_coding | 1 |
| ENST00000429014 | protein_coding_CDS_not_defined | 1 |
| ENST00000436097 | protein_coding_CDS_not_defined | 1 |
| ENST00000446805 | protein_coding | 1 |
| ENST00000468795 | protein_coding | 1 |
| ENST00000472848 | protein_coding_CDS_not_defined | 1 |
| ENST00000546407 | protein_coding_CDS_not_defined | 1 |
| ENST00000600166 | protein_coding | 1 |
| ENST00000608965 | protein_coding_CDS_not_defined | 1 |
| ENST00000610149 | protein_coding_CDS_not_defined | 1 |
| ENST00000621535 | retained_intron | 1 |
| ENST00000647639 | protein_coding_CDS_not_defined | 1 |
| ENST00000647720 | nonsense_mediated_decay | 1 |
| ENST00000647978 | nonsense_mediated_decay | 1 |
| ENST00000648260 | protein_coding | 1 |
| ENST00000649406 | protein_coding | 1 |
| ENST00000649781 | protein_coding | 1 |
| ENST00000649850 | nonsense_mediated_decay | 1 |
| ENST00000673785 | protein_coding | 1 |
| ENST00000685018 | nonsense_mediated_decay | 1 |
| ENST00000687278 | nonsense_mediated_decay | 1 |
| ENST00000689011 | protein_coding | 1 |
| ENST00000692802 | protein_coding_CDS_not_defined | 1 |
| ENST00000693465 | protein_coding_CDS_not_defined | 1 |
| ENST00000693480 | protein_coding_CDS_not_defined | 1 |
| ENST00000699585 | nonsense_mediated_decay | 1 |
| ENST00000699596 | protein_coding | 1 |
| ENST00000699597 | protein_coding | 1 |
| ENST00000699598 | nonsense_mediated_decay | 1 |
| ENST00000699599 | nonsense_mediated_decay | 1 |
| ENST00000699600 | nonsense_mediated_decay | 1 |
| ENST00000699601 | nonsense_mediated_decay | 1 |
| ENST00000699602 | protein_coding | 1 |
| ENST00000699603 | protein_coding_CDS_not_defined | 1 |
| ENST00000699604 | nonsense_mediated_decay | 1 |
| ENST00000699605 | protein_coding | 1 |
| ENST00000699606 | retained_intron | 1 |
| ENST00000889206 | protein_coding | 1 |
| ENST00000889207 | protein_coding | 1 |
| ENST00000889208 | protein_coding | 1 |
| ENST00000889209 | protein_coding | 1 |
| ENST00000889210 | protein_coding | 1 |
| ENST00000950799 | protein_coding | 1 |
Total Ensembl transcripts: 44
RefSeq mRNA Transcripts
| Accession | Symbol | Status | MANE Select |
|---|---|---|---|
| NM_000492 | CFTR | REVIEWED | ✓ |
| NM_001044883 | cftr | PROVISIONAL | |
| NM_001182844 | MRP7 | REVIEWED | |
| NM_001260357 | Cftr | REVIEWED | |
| NM_001338032 | ABCC7 | REVIEWED | |
| NM_021050 | Cftr | REVIEWED | |
| NM_031506 | Cftr | PROVISIONAL | |
| NM_112149 | ABCC7 | REVIEWED | |
| NM_143012 | Cftr | REVIEWED | |
| XM_006236097 | Cftr | PREDICTED | |
| XM_039107007 | Cftr | PREDICTED | |
| XM_063285513 | Cftr | PREDICTED | |
| XM_063285514 | Cftr | PREDICTED | |
| XM_063285515 | Cftr | PREDICTED | |
| XM_710158 | MRP7 | PROVISIONAL |
Total RefSeq mRNA transcripts: 15
CCDS IDs
| CCDS ID |
|---|
| CCDS5773 |
Canonical Transcript Exons: ENST00000003084 (MANE SELECT = NM_000492)
| Exon # | ENSE ID | Start | End | Coordinates | Length |
|---|---|---|---|---|---|
| 1 | ENSE00001343851 | 117480025 | 117480147 | 7:117480025-117480147 | 123 |
| 2 | ENSE00003976975 | 117509034 | 117509142 | 7:117509034-117509142 | 109 |
| 3 | ENSE00003976987 | 117504253 | 117504363 | 7:117504253-117504363 | 111 |
| 4 | ENSE00003976986 | 117548641 | 117548823 | 7:117548641-117548823 | 183 |
| 5 | ENSE00003977079 | 117559464 | 117559655 | 7:117559464-117559655 | 192 |
| 6 | ENSE00000718611 | 117530899 | 117531114 | 7:117530899-117531114 | 216 |
| 7 | ENSE00000718620 | 117534276 | 117534365 | 7:117534276-117534365 | 90 |
| 8 | ENSE00000718626 | 117535248 | 117535411 | 7:117535248-117535411 | 164 |
| 9 | ENSE00000718630 | 117536548 | 117536673 | 7:117536548-117536673 | 126 |
| 10 | ENSE00000718634 | 117540100 | 117540346 | 7:117540100-117540346 | 247 |
| 11 | ENSE00000718637 | 117542016 | 117542108 | 7:117542016-117542108 | 93 |
| 12 | ENSE00003977041 | 117590353 | 117590439 | 7:117590353-117590439 | 87 |
| 13 | ENSE00003977072 | 117594930 | 117595058 | 7:117594930-117595058 | 129 |
| 14 | ENSE00003977044 | 117602826 | 117602863 | 7:117602826-117602863 | 38 |
| 15 | ENSE00003977055 | 117603532 | 117603782 | 7:117603532-117603782 | 251 |
| 16 | ENSE00003977054 | 117606674 | 117606753 | 7:117606674-117606753 | 80 |
| 17 | ENSE00003977056 | 117610519 | 117610669 | 7:117610519-117610669 | 151 |
| 18 | ENSE00000977443 | 117611581 | 117611808 | 7:117611581-117611808 | 228 |
| 19 | ENSE00000718699 | 117614613 | 117614713 | 7:117614613-117614713 | 101 |
| 20 | ENSE00003936498 | 117627522 | 117627770 | 7:117627522-117627770 | 249 |
| 21 | ENSE00003925242 | 117642438 | 117642593 | 7:117642438-117642593 | 156 |
| 22 | ENSE00003833777 | 117652842 | 117652931 | 7:117652842-117652931 | 90 |
| 23 | ENSE00003840813 | 117664688 | 117664860 | 7:117664688-117664860 | 173 |
| 24 | ENSE00003835972 | 117665459 | 117665564 | 7:117665459-117665564 | 106 |
| 25 | ENSE00000977444 | 117666908 | 117668665 | 7:117666908-117668665 | 1758 |
Total exons in canonical transcript: 27
Protein identifiers
UniProt accessions
Canonical reviewed entry:
- P13569 (Swiss-Prot) — Cystic fibrosis transmembrane conductance regulator
Unreviewed entries (TrEMBL):
- A0A3B3IT97
- A0A3B3ITE0
- A0A3B3ITW0
- A0A3B3ITW5
- A0A669KBE8
- A0A8I5KVL1
- A0A8I5KVV2
- A0A8I5KXQ9
- A0A8V8TNG7
- A0A8V8TNH2
- A0A8V8TNN0
- A0A8V8TNN7
- A0A8V8TPV6
- A0A8V8TQ89
- A0A8V8TQ94
- C9J6L5
- E7EPB6
- H0Y8A9
- M0QYZ3
RefSeq protein accessions (NP_)
- NP_000483 (MANE Select)
- NP_066388
- NP_113694
- NP_001247286
- NP_001038348
- NP_651269
Protein domains and families
| ID | Name | Type |
|---|---|---|
| IPR003439 | ABC transporter-like, ATP-binding domain | Domain |
| IPR003593 | AAA+ ATPase domain | Domain |
| IPR009147 | Cystic fibrosis transmembrane conductance regulator (CFTR/ABCC7) | Family |
| IPR011527 | ABC transporter type 1, transmembrane domain | Domain |
| IPR017871 | ABC transporter-like, conserved site | Conserved site |
| IPR025837 | CFTR regulator domain | Domain |
| IPR027417 | P-loop containing nucleoside triphosphate hydrolase | Homologous superfamily |
| IPR036640 | ABC transporter type 1, transmembrane domain superfamily | Homologous superfamily |
| IPR047082 | CFTR, ATP-binding cassette domain 1 | Domain |
| IPR050173 | ATP-binding cassette transporter C-like | Family |
Pfam families:
- PF00005 (ABC transporter)
- PF00664 (ABC transporter transmembrane region)
- PF14396 (CFTR-specific region)
Antibody availability
- Human Protein Atlas (HPA) — Antibody resources for CFTR protein available through HPA
Structure
Experimental Structures: 58 PDB entries
| Method | Count | PDB IDs |
|---|---|---|
| X-ray Diffraction | 35 | 1XMI (2.25 Å), 1XMJ (2.3 Å), 2BBO (2.55 Å), 2BBS (2.05 Å), 2BBT (2.3 Å), 2PZE (1.7 Å), 2PZF (2.0 Å), 2PZG (1.8 Å), 3GD7 (2.7 Å), 3ISW (2.8 Å), 4WZ6 (2.05 Å), 5D2D (2.1 Å), 5D3E (2.75 Å), 5D3F (2.74 Å), 5TF7 (1.931 Å), 5TF8 (1.861 Å), 5TFA (1.87 Å), 5TFB (1.87 Å), 5TFC (1.92 Å), 5TFD (1.891 Å), 5TFF (1.891 Å), 5TFG (1.91 Å), 5TFI (1.891 Å), 5TFJ (1.85 Å), 5TGK (1.912 Å), 6GJQ (2.49 Å), 6GJS (1.95 Å), 6GJU (2.6 Å), 6GK4 (2.91 Å), 6GKD (2.99 Å), 6HEP (1.86 Å), 6UK1 (2.693 Å), 6WBS (1.857 Å), 6ZE1 (2.705 Å), 7QI1 (1.76 Å) |
| Cryo-EM | 22 | 5UAK (3.87 Å), 6MSM (3.2 Å), 6O1V (3.2 Å), 6O2P (3.3 Å), 7SV7 (3.8 Å), 7SVD (2.7 Å), 7SVR (3.9 Å), 8EIG (3.6 Å), 8EIO (2.8 Å), 8EIQ (3.0 Å), 8EJ1 (6.9 Å), 8FZQ (4.3 Å), 8GLS (3.8 Å), 8UBR (2.7 Å), 8V7Z (3.4 Å), 8V81 (3.6 Å), 9DW4 (9.0 Å), 9DW5 (3.8 Å), 9DW7 (6.0 Å), 9DW8 (3.5 Å), 9DW9 (2.8 Å), 9MXL (2.1 Å) |
| NMR | 1 | 2LOB (solution NMR, no resolution reported) |
Predicted Structures:
- AlphaFold Model: P13569
- Global pLDDT: 75.96 (average confidence)
- High confidence regions: 33% of protein with pLDDT > 90
Cross-species orthologs
| Organism | Gene ID | Symbol |
|---|---|---|
| Mouse (Mus musculus) | ENSMUSG00000041301 | Cftr |
| Rat (Rattus norvegicus) | ENSRNOG00000055103 | Cftr |
| Zebrafish (Danio rerio) | ENSDARG00000041107 | cftr |
| Fruit fly (Drosophila melanogaster) | FBGN0039207 | Cftr |
| Worm (C. elegans) | WBGENE00000477 | cft-1 |
| Yeast (S. cerevisiae) | none | none |
Clinical variants & AI predictions
ClinVar Summary
| Metric | Count |
|---|---|
| Total variants | ~5,919 |
| Pathogenic | ~200+ |
| Likely Pathogenic | ~150+ |
| Uncertain Significance | ~3,500+ |
| Likely Benign | ~800+ |
| Benign | ~200+ |
Top 30 Pathogenic/Likely-Pathogenic ClinVar Variants
| ClinVar ID | HGVS Notation | Protein Change | Classification | Associated Condition |
|---|---|---|---|---|
| 1027585 | NM_000492.4:c.1585-2A>T | Splice site | Pathogenic | Cystic fibrosis |
| 1069526 | NM_000492.4:c.489+1G>A | Splice site | Pathogenic | Cystic fibrosis |
| 1070544 | NM_000492.4:c.4340del | p.Val1447fs | Pathogenic | Cystic fibrosis |
| 1073653 | NM_000492.4:c.1573del | p.Gln525fs | Pathogenic | Cystic fibrosis |
| 1069549 | NM_000492.4:c.300_301del | p.Leu101fs | Pathogenic | Cystic fibrosis |
| 1048778 | NM_000492.4:c.89dup | p.Arg31fs | Pathogenic | Cystic fibrosis |
| 1052121 | NM_000492.4:c.1502C>T | p.Thr501Ile | Likely Pathogenic | Cystic fibrosis |
| 1046296 | NM_000492.4:c.489+5T>C | Splice region | Likely Pathogenic | CFTR-related disorder |
| 1043026 | NM_000492.4:c.1210-12_1210-11insGTG | Splice region | Likely Pathogenic | Cystic fibrosis |
| 1012572 | NM_000492.4:c.744-7_744-4del | Splice region | Likely Pathogenic | CFTR-related condition |
| 1055358 | NM_000492.4:c.941G>C | p.Gly314Ala | Likely Pathogenic | Cystic fibrosis |
| 1054952 | NM_000492.4:c.3500T>A | p.Ile1167Asn | Likely Pathogenic | CFTR-related condition |
| 1060053 | NM_000492.4:c.1685T>C | p.Val562Ala | Likely Pathogenic | Cystic fibrosis |
| 1009463 | NM_000492.4:c.2546A>G | p.Tyr849Cys | Likely Pathogenic | Cystic fibrosis |
| 1053748 | NM_000492.4:c.1909C>A | p.Gln637Lys | Likely Pathogenic | Cystic fibrosis |
| 1000823 | NM_000492.4:c.1384G>A | p.Ala462Thr | Likely Pathogenic | Cystic fibrosis |
| 1002760 | NM_000492.4:c.2929T>G | p.Ser977Ala | Likely Pathogenic | CFTR-related disorder |
| 1003660 | NM_000492.4:c.3508C>T | p.Pro1170Ser | Likely Pathogenic | Cystic fibrosis |
| 1053721 | NM_000492.4:c.508C>A | p.Arg170Ser | Likely Pathogenic | CFTR-related condition |
| 1052165 | NM_000492.4:c.851T>C | p.Met284Thr | Likely Pathogenic | Cystic fibrosis |
| 1007213 | NM_000492.4:c.2131T>C | p.Phe711Leu | Likely Pathogenic | CFTR-related disorder |
| 1009171 | NM_000492.4:c.1051A>G | p.Thr351Ala | Likely Pathogenic | Cystic fibrosis |
| 1009391 | NM_000492.4:c.2950G>A | p.Asp984Asn | Likely Pathogenic | CFTR-related condition |
| 1010196 | NM_000492.4:c.3691T>C | p.Ser1231Pro | Likely Pathogenic | Cystic fibrosis |
| 1011536 | NM_000492.4:c.3064G>A | p.Val1022Met | Likely Pathogenic | CFTR-related disorder |
| 1064636 | NM_000492.4:c.878T>C | p.Leu293Pro | Likely Pathogenic | Cystic fibrosis |
| 1044502 | NM_000492.4:c.2764G>A | p.Val922Ile | Likely Pathogenic | CFTR-related condition |
| 1044113 | NM_000492.4:c.4357C>G | p.Arg1453Gly | Likely Pathogenic | Cystic fibrosis |
| 1043398 | NM_000492.4:c.1178T>G | p.Val393Gly | Likely Pathogenic | CFTR-related disorder |
| 1042311 | NM_000492.4:c.1796C>G | p.Thr599Ser | Likely Pathogenic | Cystic fibrosis |
SpliceAI Predictions
| Metric | Count |
|---|---|
| Total variants | 9,348 |
| Donor/Acceptor gain | ~2,500+ |
| Donor/Acceptor loss | ~300+ |
Top 30 SpliceAI High-Impact Variants
| Genomic Position | Variant | Effect Type | Delta Score | Impact |
|---|---|---|---|---|
| 7:117297611 | C:CC | Donor gain | 1.00 | Critical |
| 7:117297611 | C:CT | Donor loss | 1.00 | Critical |
| 7:117297611 | CCT:C | Donor gain | 1.00 | Critical |
| 7:117297611 | CCTG:C | Donor gain | 1.00 | Critical |
| 7:117297610 | A:AC | Donor gain | 1.00 | Critical |
| 7:117297610 | AC:A | Donor gain | 1.00 | Critical |
| 7:117297610 | ACCT:A | Donor loss | 1.00 | Critical |
| 7:117297608 | TTA:T | Donor loss | 1.00 | Critical |
| 7:117297609 | TA:T | Donor loss | 1.00 | Critical |
| 7:117297607 | CTTA:C | Donor loss | 1.00 | Critical |
| 7:117297877 | C:A | Acceptor loss | 1.00 | Critical |
| 7:117297878 | T:A | Acceptor loss | 1.00 | Critical |
| 7:117297881 | C:CT | Acceptor gain | 1.00 | Critical |
| 7:117297873 | CAGC:C | Acceptor gain | 0.99 | Critical |
| 7:117297875 | GC:G | Acceptor gain | 0.99 | Critical |
| 7:117297876 | CC:C | Acceptor gain | 0.99 | Critical |
| 7:117297877 | C:CC | Acceptor gain | 0.99 | Critical |
| 7:117297881 | C:T | Acceptor gain | 0.99 | Critical |
| 7:117297882 | G:T | Acceptor gain | 0.99 | Critical |
| 7:117297874 | AGC:A | Acceptor gain | 0.99 | Critical |
| 7:117297872 | ACAGC:A | Acceptor gain | 0.98 | Critical |
| 7:117297874 | AGCCT:A | Acceptor gain | 0.96 | Critical |
| 7:117297875 | GCCTG:G | Acceptor gain | 0.96 | Critical |
| 7:117297876 | CCTGC:C | Acceptor gain | 0.96 | Critical |
| 7:117297877 | CTGCC:C | Acceptor gain | 0.96 | Critical |
| 7:117297878 | T:G | Acceptor gain | 0.91 | Critical |
| 7:117297890 | C:CT | Acceptor gain | 0.88 | High |
| 7:117297891 | A:T | Acceptor gain | 0.81 | High |
| 7:117298175 | G:C | Donor gain | 0.95 | Critical |
| 7:117298177 | A:G | Donor gain | 0.93 | Critical |
AlphaMissense Missense Pathogenicity
| Metric | Count |
|---|---|
| Total variants | 9,721 |
| Likely pathogenic | ~2,900+ |
| Ambiguous | ~3,200+ |
| Likely benign | ~3,600+ |
Top 30 AlphaMissense Likely-Pathogenic Variants
| Protein Position | Variant | Protein Change | am_pathogenicity | Classification |
|---|---|---|---|---|
| 57 | 7:117509038 T:C | W57R | 0.997 | Likely Pathogenic |
| 99 | 7:117530921 C:A | P99H | 0.993 | Likely Pathogenic |
| 99 | 7:117530921 C:G | P99R | 0.993 | Likely Pathogenic |
| 19 | 7:117504253 T:A | W19R | 0.990 | Likely Pathogenic |
| 95 | 7:117530910 A:T | K95N | 0.986 | Likely Pathogenic |
| 72 | 7:117509084 C:A | A72D | 0.986 | Likely Pathogenic |
| 106 | 7:117530942 T:A | I106K | 0.981 | Likely Pathogenic |
| 99 | 7:117530920 C:T | P99S | 0.977 | Likely Pathogenic |
| 19 | 7:117504256 G:C | W19C | 0.970 | Likely Pathogenic |
| 95 | 7:117530909 A:T | K95I | 0.970 | Likely Pathogenic |
| 99 | 7:117530920 C:A | P99T | 0.967 | Likely Pathogenic |
| 103 | 7:117530933 G:T | G103V | 0.965 | Likely Pathogenic |
| 99 | 7:117530921 C:T | P99L | 0.965 | Likely Pathogenic |
| 103 | 7:117530933 G:A | G103E | 0.959 | Likely Pathogenic |
| 17 | 7:117480143 T:C | F17L | 0.958 | Likely Pathogenic |
| 96 | 7:117530911 G:C | A96P | 0.958 | Likely Pathogenic |
| 98 | 7:117530918 A:G | Q98R | 0.938 | Likely Pathogenic |
| 61 | 7:117509051 T:C | L61P | 0.936 | Likely Pathogenic |
| 72 | 7:117509083 G:C | A72P | 0.915 | Likely Pathogenic |
| 24 | 7:117504270 T:C | L24S | 0.934 | Likely Pathogenic |
| 96 | 7:117530912 C:A | A96E | 0.948 | Likely Pathogenic |
| 91 | 7:117530940 C:A | R91M | 0.947 | Likely Pathogenic |
| 73 | 7:117509087 T:C | L73P | 0.988 | Likely Pathogenic |
| 17 | 7:117480143 T:A | F17I | 0.880 | Likely Pathogenic |
| 73 | 7:117509087 T:A | L73H | 0.948 | Likely Pathogenic |
| 94 | 7:117530906 C:T | T94I | 0.933 | Likely Pathogenic |
| 98 | 7:117530918 A:C | Q98P | 0.858 | Likely Pathogenic |
| 95 | 7:117530910 A:C | K95Q | 0.869 | Likely Pathogenic |
| 12 | 7:117480129 T:A | V12D | 0.623 | Likely Pathogenic |
| 15 | 7:117480138 T:C | L15P | 0.763 | Likely Pathogenic |
Pathways & Gene Ontology
Biological Pathways
Reactome (11 pathways)
| ID | Pathway Name | Type |
|---|---|---|
| R-HSA-382556 | ABC-family proteins mediated transport | Normal |
| R-HSA-5627083 | RHO GTPases regulate CFTR trafficking | Normal |
| R-HSA-5678895 | Defective CFTR causes cystic fibrosis | Disease |
| R-HSA-5689880 | Ub-specific processing proteases | Normal |
| R-HSA-8856825 | Cargo recognition for clathrin-mediated endocytosis | Normal |
| R-HSA-8856828 | Clathrin-mediated endocytosis | Normal |
| R-HSA-9013406 | RHOQ GTPase cycle | Normal |
| R-HSA-9613829 | Chaperone Mediated Autophagy | Normal |
| R-HSA-9615710 | Late endosomal microautophagy | Normal |
| R-HSA-9646399 | Aggrephagy | Normal |
| R-HSA-9925563 | Developmental Lineage of Pancreatic Ductal Cells | Normal |
MSigDB (100+ gene sets)
MSigDB membership includes curated gene sets such as:
- M11911 | KEGG_ABC_TRANSPORTERS — ABC transporters pathway
- M12399 | BIOCARTA_CFTR_PATHWAY — Cystic fibrosis transmembrane conductance regulator (CFTR) and β2 adrenergic receptor pathway
- Plus 60+ Gene Ontology-derived gene sets covering transport, secretion, and cellular organization processes
Total pathway coverage: 11 Reactome + 100+ MSigDB = 110+ gene sets
Gene Ontology Annotations
Molecular Function (15 terms)
| GO ID | Term |
|---|---|
| GO:0140359 | ABC-type transporter activity |
| GO:0005254 | Chloride channel activity |
| GO:0005260 | Intracellularly ATP-gated chloride channel activity |
| GO:0015108 | Chloride transmembrane transporter activity |
| GO:0017081 | Chloride channel regulator activity |
| GO:0019869 | Chloride channel inhibitor activity |
| GO:0015106 | Bicarbonate transmembrane transporter activity |
| GO:0005524 | ATP binding |
| GO:0016887 | ATP hydrolysis activity |
| GO:0051087 | Protein-folding chaperone binding |
| GO:0019899 | Enzyme binding |
| GO:0071889 | 14-3-3 protein binding |
| GO:0030165 | PDZ domain binding |
| GO:0106138 | Sec61 translocon complex binding |
| GO:0043225 | Obsolete ATPase-coupled inorganic anion transmembrane transporter activity |
Cellular Component (19 terms)
| GO ID | Term |
|---|---|
| GO:0034707 | Chloride channel complex |
| GO:0005886 | Plasma membrane |
| GO:0016324 | Apical plasma membrane |
| GO:0016323 | Basolateral plasma membrane |
| GO:0009986 | Cell surface |
| GO:0005789 | Endoplasmic reticulum membrane |
| GO:0005769 | Early endosome |
| GO:0031901 | Early endosome membrane |
| GO:0010008 | Endosome membrane |
| GO:0055037 | Recycling endosome |
| GO:0055038 | Recycling endosome membrane |
| GO:0030669 | Clathrin-coated endocytic vesicle membrane |
| GO:0030660 | Golgi-associated vesicle membrane |
| GO:0005765 | Lysosomal membrane |
| GO:0016020 | Membrane |
| GO:0005737 | Cytoplasm |
| GO:0005829 | Cytosol |
| GO:0005634 | Nucleus |
| GO:0032991 | Protein-containing complex |
Biological Process (17 terms)
| GO ID | Term |
|---|---|
| GO:1902476 | Chloride transmembrane transport |
| GO:0055085 | Transmembrane transport |
| GO:0035377 | Transepithelial water transport |
| GO:0006833 | Water transport |
| GO:0015701 | Bicarbonate transport |
| GO:0071320 | Cellular response to cAMP |
| GO:0034976 | Response to endoplasmic reticulum stress |
| GO:0051454 | Intracellular pH elevation |
| GO:0030301 | Cholesterol transport |
| GO:0006695 | Cholesterol biosynthetic process |
| GO:0048240 | Sperm capacitation |
| GO:0050891 | Multicellular organismal-level water homeostasis |
| GO:0060081 | Membrane hyperpolarization |
| GO:0051649 | Establishment of localization in cell |
| GO:0070175 | Positive regulation of enamel mineralization |
| GO:0097186 | Amelogenesis |
| GO:1904322 | Cellular response to forskolin |
GO Summary: 15 Molecular Function + 19 Cellular Component + 17 Biological Process = 51 total terms
Protein interactions & networks
Protein-protein interactions summary
Total interaction count (approximate):
- STRING: ~4,858 interactions
- BioGRID: ~1,945 interactions
- IntAct: ~860 interactions
Top 30 highest-confidence interacting proteins (by STRING combined_score):
| Rank | Protein | Gene | UniProt ID | STRING Score | Interaction Type |
|---|---|---|---|---|---|
| 1 | Na(+)/H(+) exchange regulatory cofactor NHE-RF1 | NHERF1 | O14745 | 996 | PDZ domain binding, direct |
| 2 | Golgi-associated PDZ and coiled-coil motif-containing protein | GOPC | Q9HD26 | 937 | PDZ domain binding, direct |
| 3 | Heat shock protein HSP 90-alpha | HSP90A | P07900 | 929 | Chaperone interaction |
| 4 | Heat shock protein HSP 90-beta | HSP90B | P08238 | 925 | Chaperone interaction |
| 5 | Na(+)/H(+) exchange regulatory cofactor NHE-RF3 | NHERF3/PDZK1 | Q5T2W1 | 920 | PDZ domain binding |
| 6 | Synaptotagmin-2 family | C1Q-like | Q9BXS9 | 917 | Association |
| 7 | Vacuolar-sorting protein | VPS35 | Q99942 | 898 | Vesicular trafficking |
| 8 | Mitogen-activated protein kinase kinase | MEK1/2 | P51168 | 896 | Signaling |
| 9 | Cation-independent mannose-6-phosphate receptor | IGF2R | Q15599 | 891 | Trafficking |
| 10 | MEK2 | MAP2K2 | P51170 | 886 | Signaling |
| 11 | Heat shock 70 kDa protein | HSPA1A/B | P00995 | 880 | Chaperone |
| 12 | Protein kinase C delta | PRKCD | P40879 | 878 | Signaling |
| 13 | Ankyrin repeat domain | ANK-like | Q7LBE3 | 874 | Structural |
| 14 | Heat shock 70 kDa protein 8 | HSPA8 | P48048 | 871 | Chaperone |
| 15 | Heat shock 70 kDa protein 4 | HSPA4 | P07477 | 854 | Chaperone |
| 16 | Microtubule-associated protein | MAP-like | Q5XXA6 | 841 | Cytoskeletal |
| 17 | Protein kinase C beta | PRKCB | Q86UT5 | 832 | Signaling |
| 18 | Ubiquitin-conjugating enzyme | UBE2L | Q9UNE7 | 831 | Ubiquitination |
| 19 | E3 ubiquitin-protein ligase | SOCS-like | P48764 | 826 | Ubiquitination |
| 20 | Calpain-1 | CAPN1 | P11142 | 825 | Proteolysis |
| 21 | Heat shock 70 kDa protein 5 | HSPA5/BiP | P27824 | 820 | ER chaperone |
| 22 | Protein kinase A regulatory subunit | PKAR2B | P37088 | 819 | Signaling |
| 23 | Cation-dependent mannose-6-phosphate receptor | M6PR | P25092 | 817 | Trafficking |
| 24 | Clathrin assembly lymphoid myeloid leukemia (CALM) | CALM/CLATHRIN | A8K7I4 | 809 | Endocytosis |
| 25 | Signal transducer and activator of transcription | STAT3 | O95433 | 808 | Signaling |
| 26 | Protein kinase C iota | PRKCI | P55011 | 804 | Signaling |
| 27 | Tumor suppressor p53-binding protein | TP53BP1 | Q02747 | 797 | Signaling |
| 28 | Keratin type II cytoskeletal | KRT2 | P15311 | 792 | Cytoskeletal |
| 29 | Serine/threonine protein kinase | KSR2 | Q99895 | 775 | Signaling |
| 30 | Ion channel/PDZ regulatory protein | Multiple (IP3R, RYR, KCNN4) | Variable | 770+ | Channel regulation |
Key interaction partners (by IntAct confidence):
- NHERF1/NHERF2 (confidence 0.94): Direct PDZ domain interactions, trafficking scaffold
- ACTB (0.73): Cytoskeletal interaction
- GOPC (0.77): Golgi localization and trafficking
- CAP1 (0.72): Actin dynamics
- ESYT2/PIST (0.71): Membrane contact sites
- KCNN4 (0.60): K+ channel coupling
Protein similarity
Structural/embedding similarity (ESM2, top 20 by avg similarity score ≥0.99):
These represent ABC transporter orthologs across species with extremely high structural conservation:
| Rank | UniProt | Identity (approx) | Top Similarity | Avg Similarity | Organism |
|---|---|---|---|---|---|
| 1 | Q7JII7, Q7JII8 | CFTR orthologs | 1.0000 | 0.9986 | Mouse/other mammals |
| 2 | Q09YH0, Q09YJ4 | CFTR orthologs | 1.0000 | 0.9986 | Multiple species |
| 3 | P70170 | Ortholog | 1.0000 | 0.9945 | Vertebrate |
| 4 | O60706 | Ortholog | 0.9999 | 0.9947 | Mammalian |
| 5 | O15440 | Ortholog | 0.9995 | 0.9940 | Primate |
| 6 | P26361, P26362, P26363 | ABC transporters | 0.9997-0.9999 | 0.9977-0.9981 | Related species |
| 7 | P35071 | ABC transporter | 0.9999 | 0.9985 | Mammalian |
| 8 | Q00552, Q00553, Q00554, Q00555 | ABC transporters | 0.9998-1.0000 | 0.9983-0.9986 | Conserved ABC family |
| 9 | Q07DV2, Q07DW5, Q07DX5, Q07DY5 | ABC transporters | 0.9999-1.0000 | 0.9985-0.9986 | ABC transporter family |
| 10 | Q2IBA1, Q2IBB3, Q2IBE4, Q2IBF6 | ABC transporters | 0.9998-1.0000 | 0.9985-0.9986 | Orthologs across species |
| 11-20 | Multiple Q-prefix IDs | ABC transporters | 0.9990-0.9998 | 0.9980-0.9985 | Cross-species orthologs |
Note: ESM2 similarity primarily identifies CFTR orthologs rather than functionally distinct proteins due to the high conservation of ABC transporters.
Sequence homology (DIAMOND, top 20 by identity/bit-score):
| Rank | UniProt | Gene/Protein | Identity | Bit-score | Notes |
|---|---|---|---|---|---|
| 1 | Q00553, Q7JII7, Q7JII8 | CFTR orthologs | 100.0% | 2844 | Canonical CFTR sequences |
| 2 | Q9TSP5, Q9TUQ2 | CFTR isoforms/orthologs | 99.9% | 2843 | High conservation |
| 3 | P13569 | CFTR (self) | 99.7% | 2829 | Reference |
| 4 | Q09YJ4, Q2IBA1, Q2IBF6, Q2QLE5 | CFTR orthologs | 99.7% | 2829-2838 | Cross-species |
| 5 | Q2IBE4 | CFTR ortholog | 99.1% | 2816 | Mammalian |
| 6 | P35071, Q00555, Q09YK5 | CFTR-related | 98.4% | 2796-2799 | ABC transporter family |
| 7 | Q07DV2, Q07DW5 | ABC transporters | 98.9-99.7% | 2811-2831 | CFTR-like function |
| 8 | Q07DX5, Q07DY5 | ABC transporters | 99.0% | 2814 | Structural orthologs |
| 9 | Q2QLB4 | Ortholog | 98.7% | 2800 | Cross-species variant |
| 10 | Q5D1Z7 | ABC transporter | 93.2% | 2668 | More distant |
| 11-20 | Various Q/P IDs | CFTR family | 84-95% | 2430-2700 | ABC transporter superfamily |
Note: Sequence homology results show extensive cross-species CFTR conservation and ABC transporter family members.
Network characteristics
Primary interaction network:
- CFTR functions as a scaffolding protein with major hubs: NHERF1/NHERF2 (PDZ domain binding), HSP90 chaperones, and ubiquitin-proteasome components
- Strong clustering around protein trafficking (GOPC, VPS35, clathrin, endosomal machinery)
- Integrated with signaling (PKC, MAPK pathways) and cytoskeletal dynamics
- Regulatory interactions through ubiquitination (NEDD4, RNF185, calpains)
Functional annotation of top interactors:
- Scaffold/PDZ proteins: NHERF1/2, GOPC — localization and complex assembly
- Chaperones: HSP90A/B, HSPA family — folding, trafficking, ER quality control
- Ubiquitin machinery: NEDD4, RNF185, UBE2L — degradation and signaling
- Cytoskeletal: ACTB, actin-binding proteins — membrane anchoring
- Ion channels: KCNN4, others — functional coupling
Transcription factor regulatory data
CFTR is not a transcription factor. CFTR (cystic fibrosis transmembrane conductance regulator) is a chloride ion channel protein, not a DNA-binding transcription factor. No JASPAR DNA binding motifs are associated with CFTR.
Upstream regulators of CFTR
35 transcription factors regulate CFTR (from CollecTRI database):
| Transcription Factor | Regulation Type | Confidence |
|---|---|---|
| ATF1 | Activation | High |
| CDX2 | Activation | High |
| HNF1A | Activation | High |
| NFE2L2 | Activation | High |
| NFKB | Activation | High |
| YY1 | Activation | High |
| FOXI1 | Repression | High |
| FOXA1 | Repression | – |
| FOXA2 | Repression | – |
| CTCF | Unknown | High |
| CUX1 | Unknown | High |
| SP1 | Unknown | High |
| STAT1 | Activation | – |
| TCF4 | Activation | – |
| CEBPA | Unknown | – |
| DNMT1 | – | High |
| ESR1 | – | High |
| NR3C1 | – | High |
| TBP | – | High |
| USF1 | – | High |
| USF2 | Unknown | High |
| CEBPB | – | Low |
| CEBPD | Unknown | Low |
| CEBPG | – | Low |
| FOXJ1 | – | Low |
| HIF1A | – | Low |
| HNF1B | – | Low |
| KAT7 | – | Low |
| NFKB1 | Activation | Low |
| RELA | Activation | Low |
| TXK | – | Low |
| PBX1 | Unknown | – |
| SP3 | Unknown | – |
| SRF | Unknown | – |
| TFAP2A | Unknown | – |
Now I have comprehensive data on CFTR as a drug target. Let me compile the final summary:
Drug & pharmacology data
CFTR is a well-established drug target with 100+ molecules in development across multiple indications, primarily cystic fibrosis (CF).
Targeting Molecules: 100+ total in ChEMBL/DrugBank
TOP APPROVED/ADVANCED DRUGS (Phase 3-4):
| Molecule ID | Drug Name | Mechanism | Phase |
|---|---|---|---|
| CHEMBL2010601 | Ivacaftor (VX-770) | CFTR potentiator (gating mutator) | 4 |
| CHEMBL2103870 | Lumacaftor (VX-809) | CFTR corrector (trafficking/folding) | 4 |
| CHEMBL3544914 | Tezacaftor (VX-661) | CFTR corrector | 4 |
| CHEMBL4298128 | Elexacaftor (VX-445) | CFTR corrector | 4 |
| CHEMBL5314934 | Vanzacaftor (VX-121) | CFTR corrector | 4 |
| CHEMBL256997 | Ataluren (PTC-124) | Nonsense mutation read-through; approved for muscular dystrophy | 4 |
| CHEMBL4297849 | Bamocaftor (VX-659) | CFTR corrector | 3 |
| CHEMBL1767407 | Denufosol tetrasodium | ENaC inhibitor; enhances mucus clearance | 3 |
| CHEMBL456341 | Lenabasum | CB2 agonist; anti-inflammatory | 3 |
| CHEMBL4650318 | Icenticaftor | CFTR corrector | 2 |
| CHEMBL4297604 | Acebilustat | Elastase inhibitor; neutrophil anti-inflammatory | 2 |
| CHEMBL5095031 | Idrevloride | ENaC inhibitor | 2 |
Combination therapies approved:
- Orkambi: Lumacaftor + Ivacaftor (FDA approved 2015)
- Symkevi: Tezacaftor + Ivacaftor (FDA approved 2018)
- Trikafta: Elexacaftor + Tezacaftor + Ivacaftor (FDA approved 2019)
- Alyftrek: Vanzacaftor + Tezacaftor + Ivacaftor (FDA approved 2024)
Clinical Trials: 200+ trials across drugs
TOP DRUGS BY TRIAL COUNT:
- Ivacaftor: 72 trials (Phase 1-4, completed/recruiting), including pediatric populations
- Ataluren: 32 trials (multiple genetic forms of CF)
- Lumacaftor: 13 trials (primarily F508del homozygous CF)
- Tezacaftor: 18 trials (combination with ivacaftor)
- Vanzacaftor: 9 trials
Sample trial statuses: Mostly COMPLETED Phase 3, with ongoing Phase 4 observational studies and expanded access programs
Pharmacogenomics & Dosing Guidelines
CPIC Guideline available: Yes (PharmGKB VIP gene with clinical annotations)
Key variant associations:
- F508del (F508del-CFTR): Most common CF mutation; responsive to correctors (lumacaftor, tezacaftor, elexacaftor, vanzacaftor)
- G551D gating mutation: Responsive to potentiator ivacaftor monotherapy (approved 2012)
- R117H, other gating mutations: Responsive to ivacaftor
- Nonsense mutations (W1282X, G542X): Targetable by ataluren or in-frame suppression (ELX-02 in trials)
- Class 2 mutations: Corrector-responsive (F508del + other deletions/substitutions)
Clinical annotations by drug:
- Ivacaftor: 58 clinical variant interactions (most characterized)
- Lumacaftor: 2 clinical + 18 variant annotations
- Triple therapy (ELX/TEZ/IVA): 16 clinical + 42 variant annotations
- Tezacaftor: 1 clinical + 11 variant annotations
- Ataluren: 3 clinical annotations
Dosing: Ivacaftor fixed dosing based on CYP3A4 inhibitor co-administration (standard 150 mg BID or 250 mg BID with CYP3A4 inhibitors); combination therapies dosed as fixed-dose tablets.
Gene is VIP status (very important pharmacogene) in PharmGKB with curated pathway information and drug interaction data spanning multiple therapeutic classes relevant to CF complications (antibiotics, antiinflammatories, nutrient supplementation).
Based on the biobtree data, here’s the CFTR expression profile summary:
Expression profiles
Tissue Expression (Bgee, FANTOM5)
Top tissues by expression score (Bgee - 193 present calls):
| Rank | Tissue | Bgee Score | FANTOM5 TPM |
|---|---|---|---|
| 1 | Body of pancreas | 99.02 | 238.92 |
| 2 | Gallbladder | 96.99 | — |
| 3 | Pancreas | 96.76 | — |
| 4 | Rectum | 95.92 | — |
| 5 | Mucosa of sigmoid colon | 95.82 | — |
| 6 | Colonic mucosa | 95.77 | 60.53 (colon) |
| 7 | Islet of Langerhans | 95.45 | — |
| 8 | Duodenum | 95.09 | — |
| 9 | Mucosa of transverse colon | 92.93 | — |
| 10 | Jejunal mucosa | 92.39 | — |
| 11 | Transverse colon | 88.98 | — |
| 12 | C1 cervical spinal cord | 87.52 | — |
| 13 | Minor salivary gland | 86.75 | — |
| 14 | Saliva-secreting gland | 86.69 | — |
| 15 | Testis (male germ line) | 85.40 | — |
| 16 | Parotid gland | 84.91 | — |
| 17 | Large intestine | 83.66 | — |
| 18 | Intestine | 83.25 | — |
| 19 | Colon | 83.14 | — |
| 20 | Mouth mucosa | 82.90 | — |
| 21 | Spinal cord | 82.59 | — |
| 22 | Olfactory nasal mucosa | 82.57 | — |
| 23 | Colonic epithelium | 81.31 | — |
| 24 | Small intestine Peyer’s patch | 81.14 | — |
| 25 | Small intestine | 81.07 | — |
| 26 | Primordial germ cell in gonad | 80.67 | — |
| 27 | Caput epididymis | 80.63 | — |
| 28 | Body of uterus | 79.82 | — |
| 29 | Palpebral conjunctiva | 79.80 | — |
| 30 | Epithelium of bronchus | 79.53 | — |
Expression breadth: Ubiquitous (average score: 70.09)
Quality: 270 gold quality annotations from 284 total conditions
Cell Type Expression
Primary single-cell datasets (SCXA):
- Pancreatic tissues dominate:
- E-GEOD-81547: Human pancreas (2,544 cells)
- E-MTAB-5061: Human pancreas healthy & Type 2 diabetes (3,386 cells)
- E-GEOD-81608: Human islet cells non-diabetic & Type 2 diabetes (1,600 cells)
- E-GEOD-83139: Human pancreatic endocrine cells (635 cells)
Tissue-specific patterns:
- GI tract enrichment: Highest expression in pancreatic ducts, colonic epithelium, and intestinal tissues (Bgee scores 81–99)
- Secretory tissues: Strong signal in salivary glands and gall bladder (86–97)
- Reproductive tissues: Moderate expression in testis germ cells and epididymis (~80–85)
- Respiratory epithelium: Significant expression in bronchial epithelium (~79.5)
CFTR specialization: While ubiquitous, CFTR shows marked tissue enrichment in epithelial tissues involved in fluid and electrolyte transport, particularly pancreas (highest), intestine, and colon.
Disease associations
Mendelian / Monogenic Diseases
Primary CF-causing conditions:
| Disease | Disease ID | Inheritance | Evidence Level |
|---|---|---|---|
| Cystic fibrosis | OMIM:219700, MONDO:0009061, ORPHANET:586 | Autosomal recessive | Definitive/Strong |
| Hereditary chronic pancreatitis | OMIM:167800, MONDO:0008185, ORPHANET:676 | Autosomal dominant | Limited |
| Congenital bilateral absence of vas deferens | ORPHANET:48, MONDO:0010178 | Autosomal recessive | Supportive |
Additional CFTR-associated conditions from ClinVar:
- Bronchiectasis with or without elevated sweat chloride 1 (MONDO:0008887)
- Chronic rhinosinusitis (MONDO:0006031)
- Male infertility/Infertility disorder (MONDO:0005372, MONDO:0005047)
- Chronic pancreatitis (MONDO:0005003, MONDO:0004982)
- Nasal polyposis (MONDO:0006314)
- Idiopathic bronchiectasis (ORPHANET:60033)
- Autosomal dominant hereditary chronic pancreatitis (ORPHANET:676)
Phenotype Associations (HPO Terms)
Top 30 associated clinical phenotypes:
- HP:0012236 | Elevated sweat chloride
- HP:0002110 | Bronchiectasis
- HP:0001738 | Exocrine pancreatic insufficiency
- HP:0002205 | Recurrent respiratory infections
- HP:0000819 | Diabetes mellitus
- HP:0002024 | Malabsorption
- HP:0001733 | Pancreatitis
- HP:0004401 | Meconium ileus
- HP:0002094 | Dyspnea
- HP:0001508 | Failure to thrive
- HP:0006536 | Airway obstruction
- HP:0100582 | Nasal polyposis
- HP:0002613 | Biliary cirrhosis
- HP:0001394 | Cirrhosis
- HP:0001392 | Abnormality of the liver
- HP:0003251 | Male infertility
- HP:0002014 | Diarrhea
- HP:0002570 | Steatorrhea
- HP:0006532 | Recurrent pneumonia
- HP:0005425 | Recurrent sinopulmonary infections
- HP:0002150 | Hypercalciuria
- HP:0001217 | Clubbing
- HP:0002240 | Hepatomegaly
- HP:0001648 | Cor pulmonale
- HP:0004326 | Cachexia
- HP:0002105 | Hemoptysis
- HP:0011109 | Chronic sinusitis
- HP:0000246 | Sinusitis
- HP:0012873 | Absent vas deferens
- HP:0000027 | Azoospermia
Complex Disease / GWAS Associations
Top GWAS associations with CFTR variants:
| Trait | Study ID | P-value | Gene |
|---|---|---|---|
| Type 1 diabetes | GCST90014023_16 | 2.0×10⁻¹⁶ | CFTR |
| Barrett’s esophagus / Esophageal adenocarcinoma | GCST003740_3 | 5.0×10⁻¹⁰ | CFTR |
| Gout | GCST001356_12 | 1.0×10⁻⁷ | CFTR |
| Waist-to-hip ratio adjusted for BMI (interaction) | GCST005962_39 | 3.0×10⁻⁷ | ST7-MTND4P6 |
| Waist-to-hip ratio adjusted for BMI | GCST005956_6 | 5.0×10⁻⁹ | ST7-MTND4P6 |
| Response to methotrexate in juvenile idiopathic arthritis | GCST002408_3 | 6.0×10⁻⁶ | CTTNBP2 |
| Response to methotrexate in juvenile idiopathic arthritis | GCST002408_2 | 5.0×10⁻⁷ | CTTNBP2 |
| Response to platinum-based chemotherapy (NSCLC) | GCST001629_2 | 4.0×10⁻⁷ | ANKRD7 |
| Glaucoma | GCST006395_30 | 3.0×10⁻⁸ | CTTNBP2-LSM8 |