FGF16

protein-coding

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

Gene summary

This gene encodes a member of a family of proteins that are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. This gene is expressed in cardiac cells and is required for proper heart development. Mutation in this gene was also observed in individuals with metacarpal 4-5 fusion. [provided by RefSeq, Mar 2014]

Previous symbols:

MANE transcript

NM_003868.3

Inheritance

XL, AD

ClinVar variants

P:4U:6B:1

Top phenotype

Metacarpal 4-5 fusion

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chrX:77,447,389-77,457,278

External References & Databases

Ensembl (ENSG00000196468)

Transcript & Mutation Effects

hg38 • Region Span ~9.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

syndactyly type 8STRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010669

Submitter: Labcorp Genetics (formerly Invitae)

syndactyly type 8SUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0010669

Submitter: Orphanet

syndactyly type 8STRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010669

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Metacarpal 4-5 fusionXL

Manifestation: Musculoskeletal

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: 23709756; 24878828

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FGF16 variants in ClinVar

5 Conditions Cataloged

not providedTotal: 9

not specifiedTotal: 5

Syndactyly type 8Total: 3

FGF16-related disordersTotal: 2

FGF16-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003868.3. 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			1 clinvar	1 clinvar		2
missense			5 clinvar			5
nonsense	2 clinvar	2 clinvar				4
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	2	2	6	1	0	11

Highest pathogenic variant AF is 0.000008988118

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 4 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003868.3	RefSeq	NP_003859.1	3	MANE Select
ENST00000439435.3	Ensembl	ENSP00000399324.2	3	MANE Select
ENST00001122578.1	Ensembl	ENSP00000792383.1	3	Standard
ENST00001132605.1	Ensembl	ENSP00000812795.1	3	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
fgf16	Danio rerio	Structure: GABAergic neuron Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

fgf16

Danio rerio

Structure: GABAergic neuron

Quality: decreased amount

abnormal

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
regulation of endothelial cell proliferation
signal transduction
cell-cell signaling
fibroblast growth factor receptor signaling pathway

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: ENST00000439435
Coding exons: 2
Length: 3122
Individuals with no LoFs: 124487
Homozygous LoFs: 1
Heterozygous LoFs: 0
Defined: 124488
p: 0.00000402

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.884	28	44.6	0.628	0.00000369	736
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000012	0.0000089	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.136

Essentials

Indispensability pred.: N
Indispensability score: 0.307