FGF5

protein-coding

fibroblast growth factor 5, the group of Receptor ligands|Fibroblast growth factor family

Gene summary

The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. This gene was identified as an oncogene, which confers transforming potential when transfected into mammalian cells. Targeted disruption of the homolog of this gene in mouse resulted in the phenotype of abnormally long hair, which suggested a function as an inhibitor of hair elongation. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

MANE transcript

NM_004464.4

Inheritance

ClinVar variants

P:6U:53B:4

Top phenotype

Trichomegaly

gnomAD constraint

pLI —, LoF o/e 1.33

Max pathogenic AF

—

Genomic locus

chr4:80,266,639-80,336,680

External References & Databases

Ensembl (ENSG00000138675)

Transcript & Mutation Effects

hg38 • Region Span ~70.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

trichomegalyNO_KNOWN

Inheritance Pattern: AR

Disease ID:MONDO:0008593

Submitter: Labcorp Genetics (formerly Invitae)

hypertrichosisSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0019280

Submitter: PanelApp Australia

familial isolated trichomegalySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0018472

Submitter: Orphanet

Clinical Genomic Database (CGD)

TrichomegalyAR

Manifestation: Dermatologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 24989505

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FGF5 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 54

TrichomegalyTotal: 6

not providedTotal: 3

FGF5-related disorderTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004464.4. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				2 clinvar		2
missense	1 clinvar		53 clinvar	2 clinvar		56
nonsense	1 clinvar	1 clinvar				2
start loss						0
frameshift		2 clinvar				2
splice donor/acceptor (+/-2bp)	1 clinvar					1
Total	3	3	53	4	0	63

Highest pathogenic variant AF is 0.000050036713

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004464.4	RefSeq	NP_004455.2	3	MANE Select
ENST00000312465.12	Ensembl	ENSP00000311697.7	3	MANE Select
NM_001291812.2	RefSeq	NP_001278741.1	2	Standard
NM_033143.2	RefSeq	NP_149134.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

PI3K-Akt signaling pathway - Homo sapiens (human)
Gastric cancer - Homo sapiens (human)
Melanoma - Homo sapiens (human)
Breast cancer - Homo sapiens (human)
Regulation of actin cytoskeleton - Homo sapiens (human)

Biological Process

MAPK cascade
cell-cell signaling
nervous system development
cell population proliferation
positive regulation of cell population proliferation

Molecular Function

protein tyrosine kinase activity
Ras guanyl-nucleotide exchange factor activity
fibroblast growth factor receptor binding
growth factor activity
1-phosphatidylinositol-3-kinase activity

Cellular Component

extracellular region
extracellular space

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000312465
Coding exons: 3
Length: 70082
Individuals with no LoFs: 125685
Homozygous LoFs: 0
Heterozygous LoFs: 63
Defined: 125748
p: 0.000251

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.600	171	150	1.14	0.00000749	1744
Missense (PolyPhen)		66	60.025	1.0995		654
Synonymous	-1.77	74	57.0	1.30	0.00000277	537
Loss of Function	-0.946	13	9.80	1.33	5.84e-7	112

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00038	0.00037	rare
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.000058	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00033	0.00033	rare
South Asian	0.00030	0.00029	rare
Other	0.00052	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays an important role in the regulation of cell proliferation and cell differentiation. Required for normal regulation of the hair growth cycle. Functions as an inhibitor of hair elongation by promoting progression from anagen, the growth phase of the hair follicle, into catagen the apoptosis-induced regression phase (By similarity). {ECO:0000250|UniProtKB:Q20FD0, ECO:0000269|PubMed:8663044}.;
Disease: DISEASE: Trichomegaly (TCMGLY) [MIM:190330]: A morphologic trait characterized by unusually long eyelashes and mild hypertrichosis of eyebrows. It can be observed in association with corneal irritation, cataracts, and hereditary spherocytosis. {ECO:0000269|PubMed:24989505}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.221

Intolerance Scores

LoFtool: 0.662
RVIS EVS: -0.03
RVIS percentile EVS: 51.92

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.155

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium