FGF3

Chr 11

fibroblast growth factor 3

NCBI Gene: 2248 ENSG00000186895 UniProt: P11487

The protein encoded by FGF3 is a fibroblast growth factor that regulates embryonic development, cell proliferation, and cell differentiation, and is required for normal ear development. Mutations cause autosomal recessive congenital deafness with inner ear agenesis, microtia, and microdontia. The gene is not highly constrained against loss-of-function variants (pLI = 0.00009, LOEUF = 1.782), consistent with its recessive inheritance pattern.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

Plays an important role in the regulation of embryonic development, cell proliferation, and cell differentiation. Required for normal ear development

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtDeafness with labyrinthine aplasia, microtia and microdontia

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · deafness with labyrinthine aplasia, microtia, and microdontia · AR · ClinGen 2019

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.78

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — FGF3

Authoritative clinical overview · Recommended first read

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.78LOEUF

pLI 0.000

Z-score -0.02

OE 1.01 (0.54–1.78)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.12Z-score

OE missense 1.03 (0.90–1.18)

140 obs / 136.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.01 (0.54–1.78)

0≤0.351.4

Missense OE?1.03 (0.90–1.18)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 6 / 6.0Missense obs/exp: 140 / 136.1Syn Z: -0.00

Background carrier burden — how many people carry a rare variant somewhere in FGF3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 190

412 rare PASS variants

Rare truncating (LoF)

1 in 3,300

52 rare PASS variants

Rare synonymous (reference)

1 in 330

184 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FGF3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 300	1 in 3,400
South Asian	~43k	1 in 150	1 in 3,700
Remaining (unassigned)	~30k	1 in 170	≈ 1 in 9,500
European (Finnish)	~27k	1 in 1,400	1 in 900
Admixed American	~22k	1 in 120	≈ 1 in 8,100
African / African American	~21k	1 in 150	≈ 1 in 6,000
East Asian	~20k	1 in 190	≈ 1 in 8,600
Ashkenazi Jewish	~13k	1 in 670	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 89	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 2 of 3 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 3.? see exons ↓