GeneBe

FAP

protein-coding

fibroblast activation protein alpha, the group of DASH family

Gene summary

The protein encoded by this gene is a homodimeric integral membrane gelatinase belonging to the serine protease family. It is selectively expressed in reactive stromal fibroblasts of epithelial cancers, granulation tissue of healing wounds, and malignant cells of bone and soft tissue sarcomas. This protein is thought to be involved in the control of fibroblast growth or epithelial-mesenchymal interactions during development, tissue repair, and epithelial carcinogenesis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2014]

MANE transcript

NM_004460.5

Inheritance

—

ClinVar variants

U:97B:12

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.86

Max pathogenic AF

—

Genomic locus

chr2:162,170,684-162,245,151

External References & Databases

Ensembl (ENSG00000078098)NCBI Gene (2191)OMIM (600403)HGNC:3590GenCCUniProt (Q12884)AlphaFoldClinVar (FAP)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~74.5 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FAP variants in ClinVar

2 Conditions Cataloged
not specifiedTotal: 96
not providedTotal: 11

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004460.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
2
clinvar
4
clinvar
 6
missense
95
clinvar
4
clinvar
2
clinvar
 101
nonsense
1
clinvar
 1
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
1
clinvar
 1
Total009766109
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 29 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_004460.5RefSeqNP_004451.226MANE Select
ENST00000188790.9EnsemblENSP00000188790.426MANE Select
NM_001291807.3RefSeqNP_001278736.125Standard
ENST00000422436.5EnsemblENSP00000417028.12Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

  • angiogenesis
  • proteolysis
  • cell adhesion
  • regulation of collagen catabolic process
  • negative regulation of extracellular matrix disassembly

Molecular Function

  • protease binding
  • endopeptidase activity
  • metalloendopeptidase activity
  • serine-type endopeptidase activity
  • integrin binding

Cellular Component

  • extracellular space
  • cytoplasm
  • plasma membrane
  • focal adhesion
  • cell surface

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000188790
Coding exons
26
Length
74468
Individuals with no LoFs
125663
Homozygous LoFs
0
Heterozygous LoFs
85
Defined
125748
p
0.000338
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.4543713960.9360.00001964967
Missense (PolyPhen)145168.510.860492165
Synonymous-0.3241421371.040.000007511335
Loss of Function0.9394754.50.8630.00000255681

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000370.00037rare
Latino/Admixed American0.000380.00038rare
Ashkenazi Jewish00.0absent
East Asian0.000280.00027rare
Finnish0.000140.00014rare
European (Non-Finnish)0.000420.00041rare
South Asian0.000380.00036rare
Other00.0absent

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.945

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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