FGF5

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

Basic information

Region (hg38): 4:80266638-80336680

Links

ENSG00000138675 ∙ NCBI:2250 ∙ OMIM:165190 ∙ HGNC:3683 ∙ Uniprot:P12034 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• trichomegaly (No Known Disease Relationship), mode of inheritance: AR
• familial isolated trichomegaly (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Trichomegaly	AR	General	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	Dermatologic	24989505

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FGF5 gene.

• Inborn genetic diseases (17 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FGF5 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						0
missense			16	1		17
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	16	1	0

Variants in FGF5

This is a list of pathogenic ClinVar variants found in the FGF5 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-80266888-G-A		not specified	Uncertain significance (Apr 06, 2022)
4-80266907-C-T		not specified	Uncertain significance (Jun 09, 2022)
4-80266908-C-T		FGF5-related disorder	Likely benign (Feb 21, 2019)
4-80266930-G-A		not specified	Uncertain significance (Mar 16, 2022)
4-80266969-A-G		not specified	Uncertain significance (Dec 14, 2023)
4-80266982-CTA-C		Trichomegaly	Pathogenic (Jul 22, 2014)
4-80267031-C-T		FGF5-related disorder	Likely benign (Oct 28, 2019)
4-80267060-T-G		not specified	Uncertain significance (Jul 20, 2022)
4-80267067-G-T		FGF5-related disorder	Likely benign (Feb 26, 2022)
4-80267134-T-C		not specified	Uncertain significance (Oct 18, 2021)
4-80267163-C-G		not specified	Uncertain significance (Nov 08, 2022)
4-80274951-T-C		not specified	Uncertain significance (Jan 31, 2024)
4-80274959-G-A		not specified	Uncertain significance (Dec 13, 2022)
4-80274981-C-T		not specified	Uncertain significance (Sep 15, 2021)
4-80275012-TG-T		Trichomegaly	Pathogenic (Jul 22, 2014)
4-80286341-A-T		not specified	Uncertain significance (May 17, 2023)
4-80286385-T-C		Trichomegaly	Pathogenic (Jul 22, 2014)
4-80286388-G-T		not specified	Uncertain significance (May 06, 2022)
4-80286410-A-G		not specified	Uncertain significance (Nov 09, 2021)
4-80286415-A-C		not specified	Uncertain significance (Aug 08, 2023)
4-80286464-G-A		not specified	Uncertain significance (Jan 03, 2024)
4-80286475-C-T		not specified	Uncertain significance (Jan 18, 2022)
4-80286487-C-A		not specified	Uncertain significance (Feb 06, 2023)
4-80286554-C-T		not specified	Uncertain significance (Aug 08, 2023)
4-80286603-G-C		not specified	Uncertain significance (Mar 03, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FGF5	protein_coding	protein_coding	ENST00000312465	3	70082

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.08e-10	0.0194	125685	0	63	125748	0.000251

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.600	171	150	1.14	0.00000749	1744
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000523	0.000517
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.0000583	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000331	0.000325
Middle Eastern	0.0000583	0.0000544
South Asian	0.000300	0.000294
Other	0.000519	0.000489

dbNSFP

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.
• Pathway: 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);Rap1 signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);MECP2 and Associated Rett Syndrome;MAPK Signaling Pathway;ESC Pluripotency Pathways;PI3K-Akt Signaling Pathway;Regulation of Actin Cytoskeleton;FGFR2c ligand binding and activation;FGFR2 ligand binding and activation;FRS-mediated FGFR2 signaling;Negative regulation of FGFR2 signaling;Signaling by FGFR2;Phospholipase C-mediated cascade; FGFR2;FGFR3c ligand binding and activation;SHC-mediated cascade:FGFR2;FRS-mediated FGFR3 signaling;PI-3K cascade:FGFR2;Downstream signaling of activated FGFR2;SHC-mediated cascade:FGFR3;PI-3K cascade:FGFR3;Downstream signaling of activated FGFR3;Disease;Negative regulation of FGFR3 signaling;Signaling by FGFR3;Signal Transduction;Signaling by FGFR;FGFR3 ligand binding and activation;FGFR3 mutant receptor activation;PI3K Cascade;IRS-mediated signalling;Insulin receptor signalling cascade;Activated point mutants of FGFR2;Signaling by Insulin receptor;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;FGF;Signaling by FGFR2 in disease;GPCR signaling-G alpha s Epac and ERK;GPCR signaling-G alpha s PKA and ERK;Signaling by activated point mutants of FGFR3;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;PIP3 activates AKT signaling;PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling;Negative regulation of the PI3K/AKT network;FGFR2 mutant receptor activation;Signaling by FGFR3 point mutants in cancer;Signaling by FGFR3 in disease;Signaling by FGFR in disease;Constitutive Signaling by Aberrant PI3K in Cancer;PI3K/AKT Signaling in Cancer;GPCR signaling-G alpha i;IRS-related events triggered by IGF1R;IGF1R signaling cascade;Signaling by activated point mutants of FGFR1;FGFR1 mutant receptor activation;Signaling by FGFR1 in disease;Signaling by Receptor Tyrosine Kinases;Intracellular signaling by second messengers;Phospholipase C-mediated cascade: FGFR1;Diseases of signal transduction;Downstream signaling of activated FGFR1;Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R);FGFR1c ligand binding and activation;FGFR1 ligand binding and activation;FGFRL1 modulation of FGFR1 signaling;FRS-mediated FGFR1 signaling;SHC-mediated cascade:FGFR1;PI-3K cascade:FGFR1;Negative regulation of FGFR1 signaling;Signaling by FGFR1;Phospholipase C-mediated cascade; FGFR3 (Consensus)

Recessive Scores

• pRec: 0.221

Intolerance Scores

• loftool: 0.662
• rvis_EVS: -0.03
• rvis_percentile_EVS: 51.92

Haploinsufficiency Scores

• pHI: 0.941
• hipred: Y
• hipred_score: 0.693
• ghis: 0.387

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.155

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fgf5
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Gene ontology

• Biological process: MAPK cascade;cell-cell signaling;nervous system development;cell population proliferation;positive regulation of cell population proliferation;fibroblast growth factor receptor signaling pathway;glial cell differentiation;regulation of signaling receptor activity;peptidyl-tyrosine phosphorylation;signal transduction involved in regulation of gene expression;phosphatidylinositol-3-phosphate biosynthetic process;phosphatidylinositol phosphorylation;positive regulation of cell division;positive regulation of protein kinase B signaling
• Cellular component: extracellular region;extracellular space
• 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;phosphatidylinositol-4,5-bisphosphate 3-kinase activity