Protein:CFTR |
Protein Summary |
 Gene summary |
| Gene name: CFTR | ASpdb.0 ID: 1080 | Gene | Gene symbol | CFTR | Gene ID | 1080 |
| Gene name | CF transmembrane conductance regulator |
| Synonyms | ABC35|ABCC7|CF|CFTR/MRP|MRP7|TNR-CFTR|dJ760C5.1 |
| Cytomap | 7q31.2 |
| Type of gene | protein-coding |
| Description | cystic fibrosis transmembrane conductance regulatorcAMP-dependent chloride channelchannel conductance-controlling ATPasecystic fibrosis transmembrane conductance regulatingcystic fibrosis transmembrane conductance regulator (ATP-binding cassette sub-f |
| Modification date | 20240407 |
| UniProtAcc | P13569 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | CFTR | GO:0005254 | chloride channel activity | 11524016|11707463|15010471|18570918|19019741|22178883 |
| Gene | CFTR | GO:0005737 | cytoplasm | 18570918 |
| Gene | CFTR | GO:0005769 | early endosome | 19398555 |
| Gene | CFTR | GO:0005789 | endoplasmic reticulum membrane | 11707463 |
| Gene | CFTR | GO:0005829 | cytosol | 24885604 |
| Gene | CFTR | GO:0005886 | plasma membrane | 11524016|15010471|21884936|22178883|24885604|28067262|28130590 |
| Gene | CFTR | GO:0009986 | cell surface | 20658517 |
| Gene | CFTR | GO:0015106 | bicarbonate transmembrane transporter activity | 15010471|19019741 |
| Gene | CFTR | GO:0015701 | bicarbonate transport | 15010471|19019741 |
| Gene | CFTR | GO:0016020 | membrane | 8910473 |
| Gene | CFTR | GO:0016324 | apical plasma membrane | 12801959|15247260|18570918|20658517|28130590|32487539 |
| Gene | CFTR | GO:0016887 | ATP hydrolysis activity | 8910473|11524016 |
| Gene | CFTR | GO:0019869 | chloride channel inhibitor activity | 22178883 |
| Gene | CFTR | GO:0030165 | PDZ domain binding | 11707463 |
| Gene | CFTR | GO:0032991 | protein-containing complex | 17462998 |
| Gene | CFTR | GO:0034976 | response to endoplasmic reticulum stress | 21884936|28067262 |
| Gene | CFTR | GO:0055037 | recycling endosome | 18570918 |
| Gene | CFTR | GO:0106138 | Sec61 translocon complex binding | 9792704 |
| Gene | CFTR | GO:1902476 | chloride transmembrane transport | 11524016|11707463|19019741 |
| Gene | CFTR | GO:1902943 | positive regulation of voltage-gated chloride channel activity | 22006324 |
| Gene | CFTR | GO:1904322 | cellular response to forskolin | 15010471|19621064 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| P13569-1 | P13569-1_6msm_A.pdb | 6MSM | EM | 3.2 | A | 1 | 1451 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| P13569 | CFTR | P13569-1 | P13569-3 | 1480 | 604 | 589 | 605 | Substitution | SCVCKLMANKTRILVTS | RRRCSCLLDRNKKTIF | 589 | 604 |
| P13569 | CFTR | P13569-1 | P13569-3 | 1480 | 604 | 606 | 1480 | Deletion | none | none | 604 | 604 |
| Multiple sequence alignment of our canonical and alternatively spliced CFTR |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of CFTR |
| UniProt-id | ENSG | ENST | ENSP |
| P13569-1 | ENSG00000001626.18 | ENST00000003084.11 | ENSP00000003084.6 |
| UniProt-id | NM ID | NP ID |
| P13569-1 | NM_000492.3 | NP_000483.3 |
| Amino acid sequences of our canonical and alternatively spliced CFTR |
| accession_id | Protein sequence |
| P13569-1 | MQRSPLEKASVVSKLFFSWTRPILRKGYRQRLELSDIYQIPSVDSADNLSEKLEREWDRELASKKNPKLINALRRCFFWRFMFYGIFLYL GEVTKAVQPLLLGRIIASYDPDNKEERSIAIYLGIGLCLLFIVRTLLLHPAIFGLHHIGMQMRIAMFSLIYKKTLKLSSRVLDKISIGQL VSLLSNNLNKFDEGLALAHFVWIAPLQVALLMGLIWELLQASAFCGLGFLIVLALFQAGLGRMMMKYRDQRAGKISERLVITSEMIENIQ SVKAYCWEEAMEKMIENLRQTELKLTRKAAYVRYFNSSAFFFSGFFVVFLSVLPYALIKGIILRKIFTTISFCIVLRMAVTRQFPWAVQT WYDSLGAINKIQDFLQKQEYKTLEYNLTTTEVVMENVTAFWEEGFGELFEKAKQNNNNRKTSNGDDSLFFSNFSLLGTPVLKDINFKIER GQLLAVAGSTGAGKTSLLMVIMGELEPSEGKIKHSGRISFCSQFSWIMPGTIKENIIFGVSYDEYRYRSVIKACQLEEDISKFAEKDNIV LGEGGITLSGGQRARISLARAVYKDADLYLLDSPFGYLDVLTEKEIFESCVCKLMANKTRILVTSKMEHLKKADKILILHEGSSYFYGTF SELQNLQPDFSSKLMGCDSFDQFSAERRNSILTETLHRFSLEGDAPVSWTETKKQSFKQTGEFGEKRKNSILNPINSIRKFSIVQKTPLQ MNGIEEDSDEPLERRLSLVPDSEQGEAILPRISVISTGPTLQARRRQSVLNLMTHSVNQGQNIHRKTTASTRKVSLAPQANLTELDIYSR RLSQETGLEISEEINEEDLKECFFDDMESIPAVTTWNTYLRYITVHKSLIFVLIWCLVIFLAEVAASLVVLWLLGNTPLQDKGNSTHSRN NSYAVIITSTSSYYVFYIYVGVADTLLAMGFFRGLPLVHTLITVSKILHHKMLHSVLQAPMSTLNTLKAGGILNRFSKDIAILDDLLPLT IFDFIQLLLIVIGAIAVVAVLQPYIFVATVPVIVAFIMLRAYFLQTSQQLKQLESEGRSPIFTHLVTSLKGLWTLRAFGRQPYFETLFHK ALNLHTANWFLYLSTLRWFQMRIEMIFVIFFIAVTFISILTTGEGEGRVGIILTLAMNIMSTLQWAVNSSIDVDSLMRSVSRVFKFIDMP TEGKPTKSTKPYKNGQLSKVMIIENSHVKKDDIWPSGGQMTVKDLTAKYTEGGNAILENISFSISPGQRVGLLGRTGSGKSTLLSAFLRL LNTEGEIQIDGVSWDSITLQQWRKAFGVIPQKVFIFSGTFRKNLDPYEQWSDQEIWKVADEVGLRSVIEQFPGKLDFVLVDGGCVLSHGH KQLMCLARSVLSKAKILLLDEPSAHLDPVTYQIIRRTLKQAFADCTVILCEHRIEAMLECQQFLVIEENKVRQYDSIQKLLNERSLFRQA |
| P13569-3 | MQRSPLEKASVVSKLFFSWTRPILRKGYRQRLELSDIYQIPSVDSADNLSEKLEREWDRELASKKNPKLINALRRCFFWRFMFYGIFLYL GEVTKAVQPLLLGRIIASYDPDNKEERSIAIYLGIGLCLLFIVRTLLLHPAIFGLHHIGMQMRIAMFSLIYKKTLKLSSRVLDKISIGQL VSLLSNNLNKFDEGLALAHFVWIAPLQVALLMGLIWELLQASAFCGLGFLIVLALFQAGLGRMMMKYRDQRAGKISERLVITSEMIENIQ SVKAYCWEEAMEKMIENLRQTELKLTRKAAYVRYFNSSAFFFSGFFVVFLSVLPYALIKGIILRKIFTTISFCIVLRMAVTRQFPWAVQT WYDSLGAINKIQDFLQKQEYKTLEYNLTTTEVVMENVTAFWEEGFGELFEKAKQNNNNRKTSNGDDSLFFSNFSLLGTPVLKDINFKIER GQLLAVAGSTGAGKTSLLMVIMGELEPSEGKIKHSGRISFCSQFSWIMPGTIKENIIFGVSYDEYRYRSVIKACQLEEDISKFAEKDNIV |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| CFTR (go to UniProt):P13569 |
| Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| P13569 | Topological domain | 359 | 858 | Note=Cytoplasmic;Ontology_term=ECO:0000269;evidence=ECO:0000269|Ref.55 | Type=Substitution;Start=589;End=605 |
| P13569 | Topological domain | 359 | 858 | Note=Cytoplasmic;Ontology_term=ECO:0000269;evidence=ECO:0000269|Ref.55 | Type=Deletion;Start=606;End=1480 |
| P13569 | Transmembrane | 859 | 879 | Note=Helical%3B Name%3D7;Ontology_term=ECO:0000269;evidence=ECO:0000269|Ref.55 | Type=Deletion;Start=606;End=1480 |
| P13569 | Topological domain | 880 | 918 | Note=Extracellular;Ontology_term=ECO:0000269;evidence=ECO:0000269|Ref.55 | Type=Deletion;Start=606;End=1480 |
| P13569 | Transmembrane | 919 | 939 | Note=Discontinuously helical%3B Name%3D8;Ontology_term=ECO:0000269;evidence=ECO:0000269|Ref.55 | Type=Deletion;Start=606;End=1480 |
| P13569 | Topological domain | 940 | 990 | Note=Cytoplasmic;Ontology_term=ECO:0000269;evidence=ECO:0000269|Ref.55 | Type=Deletion;Start=606;End=1480 |
| P13569 | Transmembrane | 991 | 1011 | Note=Helical%3B Name%3D9;Ontology_term=ECO:0000269;evidence=ECO:0000269|Ref.55 | Type=Deletion;Start=606;End=1480 |
| P13569 | Topological domain | 1012 | 1013 | Note=Extracellular;Ontology_term=ECO:0000269;evidence=ECO:0000269|Ref.55 | Type=Deletion;Start=606;End=1480 |
| P13569 | Transmembrane | 1014 | 1034 | Note=Helical%3B Name%3D10;Ontology_term=ECO:0000269;evidence=ECO:0000269|Ref.55 | Type=Deletion;Start=606;End=1480 |
| P13569 | Topological domain | 1035 | 1095 | Note=Cytoplasmic;Ontology_term=ECO:0000269;evidence=ECO:0000269|Ref.55 | Type=Deletion;Start=606;End=1480 |
| P13569 | Transmembrane | 1096 | 1116 | Note=Helical%3B Name%3D11;Ontology_term=ECO:0000269;evidence=ECO:0000269|Ref.55 | Type=Deletion;Start=606;End=1480 |
| P13569 | Topological domain | 1117 | 1130 | Note=Extracellular;Ontology_term=ECO:0000269;evidence=ECO:0000269|Ref.55 | Type=Deletion;Start=606;End=1480 |
| P13569 | Transmembrane | 1131 | 1151 | Note=Helical%3B Name%3D12;Ontology_term=ECO:0000269;evidence=ECO:0000269|Ref.55 | Type=Deletion;Start=606;End=1480 |
| P13569 | Topological domain | 1152 | 1480 | Note=Cytoplasmic;Ontology_term=ECO:0000269;evidence=ECO:0000269|Ref.55 | Type=Deletion;Start=606;End=1480 |
| P13569 | Domain | 423 | 646 | Note=ABC transporter 1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00434 | Type=Substitution;Start=589;End=605 |
| P13569 | Domain | 423 | 646 | Note=ABC transporter 1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00434 | Type=Deletion;Start=606;End=1480 |
| P13569 | Domain | 859 | 1155 | Note=ABC transmembrane type-1 2;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00441 | Type=Deletion;Start=606;End=1480 |
| P13569 | Domain | 1210 | 1443 | Note=ABC transporter 2;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00434 | Type=Deletion;Start=606;End=1480 |
| P13569 | Region | 654 | 831 | Note=Disordered R region;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:10792060;Dbxref=PMID:10792060 | Type=Deletion;Start=606;End=1480 |
| P13569 | Region | 1386 | 1480 | Note=Interaction with GORASP2;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:21884936;Dbxref=PMID:21884936 | Type=Deletion;Start=606;End=1480 |
| P13569 | Region | 1452 | 1480 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=606;End=1480 |
| P13569 | Motif | 1478 | 1480 | "Note=PDZ-binding;Ontology_term=ECO:0000269 | ECO:0000269;evidence=ECO:0000269|PubMed:11707463 |
| P13569 | Compositional bias | 1463 | 1480 | Note=Basic and acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=606;End=1480 |
Gene Isoform Structures and Expression Levels for CFTR |
| Gene structures of our canonical and alternative spliced genes of CFTR * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
 |
| Expression levels of gene isoforms across TCGA. |
 |
Protein Structures |
| PDB and CIF files of the predicted protein structures * Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| 3D view using mol* of P13569-1 |
| 3D view using mol* of P13569-3 |
pLDDT Score Distribution |
| pLDDT score distribution of the predicted protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
| pLDDT distribution across the protein length of P13569-1 |
 |
| pLDDT distribution across the protein length of P13569-3 |
 |
Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of P13569-1 |
 |
| Ramachandran plot of P13569-3 |
 |
Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| P13569-1 | 1.157 | 220 | 1.186 | 752.542 | 0.443 | 0.886 | 1.1 | 1.441 | 0.876 | 1.645 | 0.863 | 88,95,98,99,102,127,131,134,138,139,142,200,310,31 1,337,340,341,344,345,347,348,917,920,921,923,924, 997,1000,1001,1004,1097,1100,1104,1107,1111,1137,1 138,1139,1141,1142,1144,1145,1148 |
| P13569-3 | 1.194 | 74 | 1.285 | 127.939 | 0.333 | 0.896 | 1.184 | 4.486 | 0.188 | 23.849 | 2.27 | 70,73,74,77,78,81,148,152,191,195,198,360,361,364, 365,368 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
 |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of P13569-1_P13569-1_6msm_A.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P13569-1_6msm_A_P13569-3.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P13569-1_P13569-3.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P13569-1_vs_P13569-3.png |
 < |
| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P13569-1_vs_P13569-3.png |
 < |
Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| P13569 | Region | 1386 | 1480 | Note=Interaction with GORASP2;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:21884936;Dbxref=PMID:21884936 | Type=Deletion;Start=606;End=1480 |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to CFTR |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P13569 | CFTR | DB06266 | Lonidamine | investigational | |
| P13569 | CFTR | DB00887 | Bumetanide | approved | antagonist |
| P13569 | CFTR | DB04395 | Phosphoaminophosphonic Acid-Adenylate Ester | experimental | |
| P13569 | CFTR | DB01016 | Glyburide | approved | antagonist |
| P13569 | CFTR | DB04941 | Crofelemer | approved | antagonist |
| P13569 | CFTR | DB08820 | Ivacaftor | approved | potentiator |
| P13569 | CFTR | DB09280 | Lumacaftor | approved | modulator |
| P13569 | CFTR | DB02587 | Colforsin | experimental, investigational | inhibitor |
| P13569 | CFTR | DB01050 | Ibuprofen | approved | inhibitor |
| P13569 | CFTR | DB00171 | ATP | investigational, nutraceutical | cofactor |
| P13569 | CFTR | DB09213 | Dexibuprofen | approved, investigational | inhibitor |
| P13569 | CFTR | DB01645 | Genistein | investigational | activator |
| P13569 | CFTR | DB11712 | Tezacaftor | approved, investigational | positive allosteric modulator |
| P13569 | CFTR | DB15444 | Elexacaftor | approved, investigational | positive allosteric modulator |
| P13569 | CFTR | DB04522 | Dexfosfoserine | experimental |
Related Diseases to CFTR |
| Previous studies relating to the alternative splicing of CFTR and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| CFTR | 7678008 | Alternative splicing of intron 23 of the human cystic fibrosis transmembrane conductance regulator gene resulting in a novel exon and transcript coding for a shortened intracytoplasmic C terminus. | The cystic fibrosis transmembrane conductance regulator (CFTR) gene, the gene responsible for the lethal hereditary disorder cystic fibrosis, codes for a membrane protein functioning as a cAMP-regulated Cl- channel. Evaluation of human CFTR mRNA transcripts from epithelial and nonepithelial cells demonstrated a CFTR cDNA containing a 260-base pair (bp) insertion between the known CFTR exons 23 and 24, introducing a premature stop codon that would result in a CFTR protein shortened by 61 amino acids at the carboxyl terminus compared to that expected from the normal reported human CFTR coding sequences. Sequence analysis of intron 23 of the CFTR gene demonstrated that the 260-bp insertion (named exon 24a), a part of the reported intron 23 and located consecutive to exon 24, is likely generated by an alternative splice acceptor site. The exon 24a+ CFTR mRNA transcripts represented 3-16% of the total CFTR transcripts in epithelial and nonepithelial cells. These observations suggest an unexpected plasticity of expression of the CFTR gene, where alternative splicing of precursor CFTR mRNA transcripts permits the use of an alternative exon derived from a genomic segment previously believed to function as an intron. | D003550 | Cystic Fibrosis |
| CFTR | 7684642 | Alternative splicing in the first nucleotide binding fold of CFTR. | CFTR mRNA transcripts were analyzed from freshly isolated nasal epithelial cells and lymphocytes (six individuals) and from lymphocytes alone from 14 further individuals. In four of these 20 individuals alternative splicing was observed within the region coding for the first nucleotide binding fold. The RNA sequence between exons 10 and 13 was converted to cDNA and amplified by the polymerase chain reaction (PCR). We detected two PCR products of 583 bp and 464 bp in length. Direct sequencing of both fragments showed that the 583 bp PCR fragment contained an additional 119 bp sequence between exon 10 and exon 11, directly at the normal junction. This insertion contains an in frame stop codon and would, if translated, cause a shift in the reading frame. This stop codon does not result in an undetectable mRNA level as seen with other nonsense mutations within the same region of the CFTR gene (1, 2, own unpublished results). The alternatively spliced mRNA was found to be transcribed from both CF and normal alleles. The 119 bp fragment was amplified from genomic DNA and from the genomic phage TE24V, which includes exon 9, intron 9, exon 10 and a part of intron 10 (3) by PCR using primers created from within the inserted sequence. In addition, the insertion was mapped to a 1Kb EcoRI fragment of phage TE24V by Southern-blot analysis. By sequencing the insert surroundings within the phage TE24V we identified consensus splice sites (donor and acceptor sites, branch point). Furthermore no alterations were detected in the splice site sequences between individuals who express the aberrantly spliced product and those who do not. | D003550 | Cystic Fibrosis |
| CFTR | 7689062 | Alternative splicing of a previously unidentified CFTR exon introduces an in-frame stop codon 5' of the R region. | The cystic fibrosis transmembrane conductance regulator (CFTR) has been extensively characterized as the carrier of the basic defect in cystic fibrosis. CFTR is part of a growing family of proteins encoded by a single gene, the variant isoforms of which are generated by alternative splicing or RNA editing. We have analyzed the CFTR mRNA in the region of exons 10-11 in T84 cells and detected an alternatively spliced exon (10b) accounting for about 5% of the CFTR mRNA. The exon 10b found in both the human and mice genomes, introduces an in-frame stop codon. The resulting mRNA is translated into a truncated CFTR protein, identified in T84 cells by immunoprecipitation with the CFTR-specific monoclonal antibody MATG 1061. The insertion of a differentially spliced exon carrying an in-frame stop codon is a novel cellular mechanism for the production of a protein sharing common sequences with another, but having different properties and functions. | D003110 | Colonic Neoplasms |
| CFTR | 10766763 | Splicing factors induce cystic fibrosis transmembrane regulator exon 9 skipping through a nonevolutionary conserved intronic element. | In monosymptomatic forms of cystic fibrosis such as congenital bilateral absence of vas deferens, variations in the TG(m) and T(n) polymorphic repeats at the 3' end of intron 8 of the cystic fibrosis transmembrane regulator (CFTR) gene are associated with the alternative splicing of exon 9, which results in a nonfunctional CFTR protein. Using a minigene model system, we have previously shown a direct relationship between the TG(m)T(n) polymorphism and exon 9 splicing. We have now evaluated the role of splicing factors in the regulation of the alternative splicing of this exon. Serine-arginine-rich proteins and the heterogeneous nuclear ribonucleoprotein A1 induced exon skipping in the human gene but not in its mouse counterpart. The effect of these proteins on exon 9 exclusion was strictly dependent on the composition of the TG(m) and T(n) polymorphic repeats. The comparative and functional analysis of the human and mouse CFTR genes showed that a region of about 150 nucleotides, present only in the human intron 9, mediates the exon 9 splicing inhibition in association with exonic regulatory elements. This region, defined as the CFTR exon 9 intronic splicing silencer, is a target for serine-arginine-rich protein interactions. Thus, the nonevolutionary conserved CFTR exon 9 alternative splicing is modulated by the TG(m) and T(n) polymorphism at the 3' splice region, enhancer and silencer exonic elements, and the intronic splicing silencer in the proximal 5' intronic region. Tissue levels and individual variability of splicing factors would determine the penetrance of the TG(m)T(n) locus in monosymptomatic forms of cystic fibrosis. | D003550 | Cystic Fibrosis |
| CFTR | 15379964 | CFTR mutations and polymorphisms in male infertility. | Apart from cystic fibrosis, mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are also involved in congenital bilateral absence of the vas deferens (CBAVD). A mutation is identified in about 80% of the CFTR genes derived from CBAVD patients; the genetic defect in the remainder is yet unknown. In contrast to CF patients, when CFTR is involved, at least one of the mutant CFTR genes of CBAVD patients harbors a mild mutation. A polyvariant mutant CFTR gene is the most frequent CBAVD causing mutant CFTR gene. Here, combinations of particular alleles at several polymorphic loci yield insufficient functional CFTR. The fact that most CBAVD patients, that carry mutations on both CFTR genes, have no lung disease is most probably explained by tissue specific alternative splicing, which is increased in vas deferens compared to bronchial tissue. It has also been reported that CBAVD may be involved in other forms of infertility than CBAVD, however this has not always been confirmed in other studies. Because of techniques such as intracytoplasmic sperm injection, CBAVD patients are now able to father children, however such couples have an increased risk of having a child with cystic fibrosis, and therefore genetic testing and counselling should be provided. | D007248 | Infertility, Male |
Clinically important variants in CFTR |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
| P13569 | P13569-1 | CFTR | Deletion | p.Phe508del | Pathogenic |
| P13569 | P13569-1 | CFTR | Deletion | p.Phe508del | Pathogenic |
| P13569 | P13569-1 | CFTR | Duplication | p.Glu726Argfs | Pathogenic |
| P13569 | P13569-1 | CFTR | Duplication | p.Glu726Argfs | Pathogenic |
| P13569 | P13569-1 | CFTR | Indel | p.Arg658fs | Pathogenic |
| P13569 | P13569-1 | CFTR | Indel | p.Arg658fs | Pathogenic |
| P13569 | P13569-1 | CFTR | Indel | p.Pro936fs | Pathogenic/Likely pathogenic |
| P13569 | P13569-1 | CFTR | Indel | p.Pro936fs | Pathogenic/Likely pathogenic |
Copyright 2024-PresentThe University of Texas Health Science Center at Houston (UTHealth Houston) Web File Viewing | Emergency Information |