MGP

Chr 12

matrix Gla protein

Also known as: GIG36, MGLAP, NTI

NCBI Gene: 4256ENSG00000111341UniProt: P08493

This gene encodes a member of the osteocalcin/matrix Gla family of proteins. The encoded vitamin K-dependent protein is secreted by chondrocytes and vascular smooth muscle cells, and functions as a physiological inhibitor of ectopic tissue calcification. Carboxylation status of the encoded protein is associated with calcification of the vasculature in human patients with cardiovascular disease and calcification of the synovial membranes in osteoarthritis patients. Mutations in this gene cause Keutel syndrome in human patients, which is characterized by abnormal cartilage calcification, peripheral pulmonary stenosis and facial hypoplasia. [provided by RefSeq, Sep 2016]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtKeutel syndrome

Clinical highlights

Gene-disease validity (ClinGen)
Keutel syndrome · ARDefinitivesufficient evidence for diagnostic panels
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.
1
Active trials
152
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
1.66
LOEUF
LOF
Mechanism· G2P
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?
1.66LOEUF
pLI 0.000
Z-score 0.21
OE 0.92 (0.52–1.66)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
0.12Z-score
OE missense 0.96 (0.79–1.18)
69 obs / 71.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.92 (0.52–1.66)
0≤0.351.4
Missense OE?0.96 (0.79–1.18)
0≤0.61.4
Synonymous OE?1.05
0≤1.21.6
LoF obs/exp: 7 / 7.6Missense obs/exp: 69 / 71.8Syn Z: -0.20

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

MGP · 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

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