FAP
fibroblast activation protein alpha, the group of DASH family
Basic information
Region (hg38): 2:162170684-162245151
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (85 variants)
- not_provided (11 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the FAP gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004460.5. 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 | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 5 | |||||
| missense | 83 | 88 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 83 | 4 | 6 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| FAP | protein_coding | protein_coding | ENST00000188790 | 26 | 74468 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.90e-28 | 0.00221 | 125663 | 0 | 85 | 125748 | 0.000338 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.454 | 371 | 396 | 0.936 | 0.0000196 | 4967 |
| Missense in Polyphen | 145 | 168.51 | 0.86049 | 2165 | ||
| Synonymous | -0.324 | 142 | 137 | 1.04 | 0.00000751 | 1335 |
| Loss of Function | 0.939 | 47 | 54.5 | 0.863 | 0.00000255 | 681 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000758 | 0.000754 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000278 | 0.000272 |
| Finnish | 0.000139 | 0.000139 |
| European (Non-Finnish) | 0.000422 | 0.000413 |
| Middle Eastern | 0.000278 | 0.000272 |
| South Asian | 0.000382 | 0.000359 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammation and tumor growth. Both plasma membrane and soluble forms exhibit post-proline cleaving endopeptidase activity, with a marked preference for Ala/Ser-Gly-Pro-Ser/Asn/Ala consensus sequences, on substrate such as alpha-2-antiplasmin SERPINF2 and SPRY2 (PubMed:14751930, PubMed:16223769, PubMed:16480718, PubMed:16410248, PubMed:17381073, PubMed:18095711, PubMed:21288888, PubMed:24371721). Degrade also gelatin, heat-denatured type I collagen, but not native collagen type I and IV, vibronectin, tenascin, laminin, fibronectin, fibrin or casein (PubMed:9065413, PubMed:2172980, PubMed:7923219, PubMed:10347120, PubMed:10455171, PubMed:12376466, PubMed:16223769, PubMed:16651416, PubMed:18095711). Have also dipeptidyl peptidase activity, exhibiting the ability to hydrolyze the prolyl bond two residues from the N-terminus of synthetic dipeptide substrates provided that the penultimate residue is proline, with a preference for Ala-Pro, Ile-Pro, Gly-Pro, Arg-Pro and Pro-Pro (PubMed:10347120, PubMed:10593948, PubMed:16175601, PubMed:16223769, PubMed:16651416, PubMed:16410248, PubMed:17381073, PubMed:21314817, PubMed:24371721, PubMed:24717288). Natural neuropeptide hormones for dipeptidyl peptidase are the neuropeptide Y (NPY), peptide YY (PYY), substance P (TAC1) and brain natriuretic peptide 32 (NPPB) (PubMed:21314817). The plasma membrane form, in association with either DPP4, PLAUR or integrins, is involved in the pericellular proteolysis of the extracellular matrix (ECM), and hence promotes cell adhesion, migration and invasion through the ECM. Plays a role in tissue remodeling during development and wound healing. Participates in the cell invasiveness towards the ECM in malignant melanoma cancers. Enhances tumor growth progression by increasing angiogenesis, collagen fiber degradation and apoptosis and by reducing antitumor response of the immune system. Promotes glioma cell invasion through the brain parenchyma by degrading the proteoglycan brevican. Acts as a tumor suppressor in melanocytic cells through regulation of cell proliferation and survival in a serine protease activity-independent manner. {ECO:0000250|UniProtKB:P97321, ECO:0000269|PubMed:10347120, ECO:0000269|PubMed:10455171, ECO:0000269|PubMed:10593948, ECO:0000269|PubMed:12376466, ECO:0000269|PubMed:14751930, ECO:0000269|PubMed:16175601, ECO:0000269|PubMed:16223769, ECO:0000269|PubMed:16410248, ECO:0000269|PubMed:16480718, ECO:0000269|PubMed:16651416, ECO:0000269|PubMed:17105646, ECO:0000269|PubMed:17381073, ECO:0000269|PubMed:18095711, ECO:0000269|PubMed:20707604, ECO:0000269|PubMed:21288888, ECO:0000269|PubMed:21314817, ECO:0000269|PubMed:2172980, ECO:0000269|PubMed:24371721, ECO:0000269|PubMed:24717288, ECO:0000269|PubMed:7923219, ECO:0000269|PubMed:9065413}.;
Recessive Scores
- pRec
- 0.244
Intolerance Scores
- loftool
- 0.471
- rvis_EVS
- -1.11
- rvis_percentile_EVS
- 6.86
Haploinsufficiency Scores
- pHI
- 0.375
- hipred
- Y
- hipred_score
- 0.548
- ghis
- 0.597
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.945
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Fap
- Phenotype
- normal phenotype;
Gene ontology
- Biological process
- angiogenesis;proteolysis;cell adhesion;regulation of collagen catabolic process;negative regulation of extracellular matrix disassembly;endothelial cell migration;proteolysis involved in cellular protein catabolic process;regulation of fibrinolysis;negative regulation of cell proliferation involved in contact inhibition;positive regulation of cell cycle arrest;mitotic cell cycle arrest;melanocyte proliferation;positive regulation of execution phase of apoptosis;melanocyte apoptotic process;negative regulation of extracellular matrix organization
- Cellular component
- extracellular space;cytoplasm;plasma membrane;focal adhesion;cell surface;integral component of membrane;lamellipodium;lamellipodium membrane;ruffle membrane;apical part of cell;basal part of cell;invadopodium membrane
- Molecular function
- protease binding;endopeptidase activity;metalloendopeptidase activity;serine-type endopeptidase activity;integrin binding;protein binding;peptidase activity;serine-type peptidase activity;dipeptidyl-peptidase activity;protein homodimerization activity;protein dimerization activity