FGF5
fibroblast growth factor 5, the group of Receptor ligands|Fibroblast growth factor family
Basic information
Region (hg38): 4:80266639-80336680
Links
Phenotypes
GenCC
Source:
- trichomegaly (No Known Disease Relationship), mode of inheritance: AR
- familial isolated trichomegaly (Supportive), mode of inheritance: AR
Clinical Genomic Database
Source:
| 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
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 | 2 | |||||
| missense | 19 | 20 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 1 | |||||
| Total | 0 | 0 | 19 | 4 | 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) | ||
| 4-80266925-C-A | not specified | Uncertain significance (Jun 03, 2024) | ||
| 4-80266930-G-A | not specified | Uncertain significance (Mar 16, 2022) | ||
| 4-80266969-A-G | not specified | Uncertain significance (Dec 14, 2023) | ||
| 4-80266978-A-G | not specified | Uncertain significance (Jun 17, 2024) | ||
| 4-80266982-CTA-C | Trichomegaly | Pathogenic (Jul 22, 2014) | ||
| 4-80267006-C-T | not specified | Uncertain significance (Dec 10, 2024) | ||
| 4-80267031-C-T | FGF5-related disorder | Likely benign (Oct 28, 2019) | ||
| 4-80267060-T-G | not specified | Uncertain significance (Nov 21, 2024) | ||
| 4-80267067-G-T | FGF5-related disorder | Likely benign (Aug 05, 2018) | ||
| 4-80267134-T-C | not specified | Uncertain significance (Oct 18, 2021) | ||
| 4-80267158-T-A | not specified | Uncertain significance (Aug 02, 2024) | ||
| 4-80267163-C-G | not specified | Uncertain significance (Nov 08, 2022) | ||
| 4-80274921-T-C | not specified | Uncertain significance (Nov 14, 2024) | ||
| 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 (Oct 20, 2024) | ||
| 4-80286410-A-G | not specified | Uncertain significance (Nov 09, 2021) | ||
| 4-80286415-A-C | not specified | Uncertain significance (Aug 08, 2023) |
GnomAD
Source:
| 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:
- 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