GDF3
Chr 12ADgrowth differentiation factor 3
Also known as: KFS3, MCOP7, MCOPCB6
This gene encodes a secreted growth factor of the TGF-beta superfamily that regulates early embryonic development, particularly ocular and skeletal formation. Autosomal dominant mutations cause Klippel-Feil syndrome, isolated microphthalmia, and microphthalmia with coloboma, affecting craniofacial and skeletal development. The gene shows low constraint to loss-of-function variation, consistent with its dominant inheritance pattern.
Primary Disease Associations & Inheritance
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
144 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 42 | 0 | 42 |
Likely Pathogenic | 0 | 2 | 2 | 0 | 4 |
VUS | 2 | 55 | 9 | 1 | 67 |
Likely Benign | 0 | 5 | 1 | 8 | 14 |
Benign | 0 | 3 | 7 | 4 | 14 |
Conflicting | — | 2 | |||
| Total | 2 | 65 | 61 | 13 | 143 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
GDF3 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools