FAP

fibroblast activation protein alpha, the group of DASH family

Basic information

Region (hg38): 2:162170684-162245151

Links

ENSG00000078098 ∙ NCBI:2191 ∙ OMIM:600403 ∙ HGNC:3590 ∙ Uniprot:Q12884 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FAP gene.

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.

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				1	4	5
missense			53	2	2	57
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					2	2
non coding					1	1
Total	0	0	53	3	7

Variants in FAP

This is a list of pathogenic ClinVar variants found in the FAP region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-162171007-A-G		not specified	Uncertain significance (Dec 14, 2022)
2-162171028-T-A		not specified	Uncertain significance (Jan 26, 2023)
2-162171051-G-A			Likely benign (Aug 22, 2018)
2-162171059-C-T		not specified	Uncertain significance (May 05, 2023)
2-162172846-C-A		not specified	Uncertain significance (Jul 02, 2024)
2-162172868-T-C			Benign (May 09, 2018)
2-162173161-C-T		not specified	Uncertain significance (Oct 04, 2022)
2-162173752-T-C		not specified	Uncertain significance (May 23, 2023)
2-162173765-G-T		not specified	Uncertain significance (Oct 26, 2022)
2-162174891-G-A		not specified	Uncertain significance (Jul 05, 2024)
2-162174951-C-T		not specified	Uncertain significance (Jul 09, 2024)
2-162174974-G-T			Benign (May 30, 2018)
2-162183446-T-C		not specified	Uncertain significance (Nov 17, 2022)
2-162183451-C-T		not specified	Uncertain significance (Nov 13, 2023)
2-162188238-T-C		not specified	Uncertain significance (Dec 02, 2021)
2-162188283-A-G		not specified	Uncertain significance (Apr 22, 2024)
2-162188302-G-C		not specified	Uncertain significance (Feb 16, 2023)
2-162188332-A-G		not specified	Uncertain significance (Dec 03, 2021)
2-162189135-G-C		not specified	Uncertain significance (Jul 08, 2024)
2-162189181-A-G			Benign (Jun 06, 2018)
2-162189722-C-T		not specified	Uncertain significance (Aug 21, 2023)
2-162189745-A-T		not specified	Uncertain significance (Mar 15, 2024)
2-162198785-G-A			Benign (Dec 31, 2019)
2-162198790-C-T		not specified	Uncertain significance (Feb 01, 2023)
2-162198802-C-T		not specified	Uncertain significance (Aug 15, 2023)

GnomAD

Source: gnomAD

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: dbNSFP

• 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