GDF6

Chr 8

growth differentiation factor 6

Also known as: BMP-13, BMP13, CDMP2, KFM, KFS, KFS1, KFSL, SGM1

NCBI Gene: 392255ENSG00000156466UniProt: Q6KF10

This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. This protein is required for normal formation of some bones and joints in the limbs, skull, and axial skeleton. Mutations in this gene are associated with Klippel-Feil syndrome, microphthalmia, and Leber congenital amaurosis. [provided by RefSeq, Sep 2016]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtKlippel-Feil syndrome 1, autosomal dominant
UniProtMicrophthalmia, isolated, 4
UniProtLeber congenital amaurosis 17
UniProtMultiple synostoses syndrome 4

Clinical highlights

Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.
0
Active trials
25
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.22
LOEUF· LoF intol.
Multiple*
Mechanism· predicted
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GeneReview available — GDF6
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
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.22LOEUF
pLI 0.988
Z-score 3.39
OE 0.00 (0.00–0.22)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
0.93Z-score
OE missense 0.83 (0.74–0.93)
204 obs / 245.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.00 (0.00–0.22)
0≤0.351.4
Missense OE?0.83 (0.74–0.93)
0≤0.61.4
Synonymous OE?1.05
0≤1.21.6
LoF obs/exp: 0 / 13.4Missense obs/exp: 204 / 245.2Syn Z: -0.39

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

GDF6 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients