FGF16

fibroblast growth factor 16, the group of Fibroblast growth factor family

Basic information

Region (hg38): X:77447389-77457278

Previous symbols: [ "MF4" ]

Links

ENSG00000196468 ∙ NCBI:8823 ∙ OMIM:300827 ∙ HGNC:3672 ∙ Uniprot:O43320 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• syndactyly type 8 (Supportive), mode of inheritance: AD
• syndactyly type 8 (Strong), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Metacarpal 4-5 fusion	XL	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	Musculoskeletal	23709756; 24878828

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FGF16 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FGF16 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		2
missense			2			2
nonsense		1				1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region						0
non coding				5	1	6
Total	0	2	2	7	1

Variants in FGF16

This is a list of pathogenic ClinVar variants found in the FGF16 region.

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

Position	Type	Phenotype	Significance	ClinVar
X-77447701-C-A			Likely benign (Nov 05, 2019)
X-77447842-A-G			Likely benign (Nov 30, 2020)
X-77454053-G-A			Likely benign (Jul 06, 2018)
X-77454154-T-TAGGAATCCTGGAGTTTATC		Syndactyly type 8	Likely pathogenic (Aug 14, 2024)
X-77454180-G-T		Neoplasm	- (-)
X-77454272-GT-G			Likely benign (Aug 28, 2019)
X-77454272-G-GT			Benign (Aug 15, 2019)
X-77454272-G-GTTT			Likely benign (Nov 12, 2020)
X-77456068-C-T			Likely benign (Jul 10, 2018)
X-77456310-C-T		FGF16-related disorder	Likely pathogenic (May 01, 2023)
X-77456368-C-A		Syndactyly type 8	Pathogenic (Sep 01, 2013)
X-77456392-T-C			Uncertain significance (Dec 28, 2023)
X-77456432-A-C			Uncertain significance (Jul 01, 2022)
X-77456433-C-T		Syndactyly type 8	Pathogenic (Sep 01, 2013)
X-77456515-A-G			Uncertain significance (-)
X-77456823-G-T			Likely benign (Jul 10, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FGF16	protein_coding	protein_coding	ENST00000439435	2	3122

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.751	0.240	124487	1	0	124488	0.00000402

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.884	28	44.6	0.628	0.00000369	736
Missense in Polyphen		9	15.676	0.57413		248
Synonymous	0.996	12	17.3	0.695	0.00000126	231
Loss of Function	1.99	0	4.60	0.00	4.36e-7	67

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000123	0.00000887
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays an important role in the regulation of embryonic development, cell proliferation and cell differentiation, and is required for normal cardiomyocyte proliferation and heart development. {ECO:0000269|PubMed:16597617}.
• Disease: DISEASE: Metacarpal 4-5 fusion (MF4) [MIM:309630]: A rare congenital malformation of the hand characterized by the partial or complete fusion of the fourth and fifth metacarpals. The anomaly occurs as an isolated trait or part of a syndrome. {ECO:0000269|PubMed:23709756, ECO:0000269|PubMed:25333065}. 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);Pathways Affected in Adenoid Cystic Carcinoma;MAPK Signaling Pathway;ESC Pluripotency Pathways;Focal Adhesion-PI3K-Akt-mTOR-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:FGFR4;PI-3K cascade:FGFR3;Downstream signaling of activated FGFR3;Disease;Negative regulation of FGFR3 signaling;Signaling by FGFR3;FGFR4 ligand binding and activation;Signal Transduction;FRS-mediated FGFR4 signaling;SHC-mediated cascade:FGFR4;Downstream signaling of activated FGFR4;Negative regulation of FGFR4 signaling;Signaling by FGFR4;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 Receptor Tyrosine Kinases;Intracellular signaling by second messengers;Diseases of signal transduction;Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R);Phospholipase C-mediated cascade; FGFR3;Phospholipase C-mediated cascade; FGFR4 (Consensus)

Recessive Scores

• pRec: 0.136

Haploinsufficiency Scores

• pHI: 0.914
• ghis: 0.408

Essentials

• gene_indispensability_pred: N
• gene_indispensability_score: 0.307

Mouse Genome Informatics

• Gene name: Fgf16
• Phenotype: cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); embryo phenotype; cellular phenotype; craniofacial phenotype; muscle phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: fgf16
• Affected structure: GABAergic neuron
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: MAPK cascade;regulation of endothelial cell proliferation;signal transduction;cell-cell signaling;fibroblast growth factor receptor signaling pathway;response to temperature stimulus;animal organ morphogenesis;regulation of signaling receptor activity;peptidyl-tyrosine phosphorylation;phosphatidylinositol-3-phosphate biosynthetic process;regulation of MAP kinase activity;phosphatidylinositol phosphorylation;positive regulation of protein kinase B signaling;positive regulation of brown fat cell proliferation;regulation of sprouting angiogenesis;positive regulation of endothelial cell chemotaxis to fibroblast growth factor
• 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