MGP
Chr 12ARmatrix Gla protein
Also known as: GIG36, MGLAP, NTI
This protein is secreted by chondrocytes and vascular smooth muscle cells and functions as a vitamin K-dependent inhibitor of ectopic tissue calcification. Mutations cause Keutel syndrome, an autosomal recessive disorder characterized by abnormal cartilage calcification, peripheral pulmonary stenosis, and facial hypoplasia. The gene shows low constraint to loss-of-function variants (pLI 0.00004, LOEUF 1.66), consistent with its recessive inheritance pattern.
Primary Disease Associations & Inheritance
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
178 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 | 1 | 0 | 39 | 0 | 40 |
Likely Pathogenic | 2 | 0 | 2 | 0 | 4 |
VUS | 2 | 34 | 14 | 1 | 51 |
Likely Benign | 0 | 3 | 41 | 11 | 55 |
Benign | 0 | 2 | 15 | 0 | 17 |
Conflicting | — | 5 | |||
| Total | 5 | 39 | 111 | 12 | 172 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in 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.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Assessing Clinical Features and Outcome of Breast Cancer in PALB2 Mutation Carriers: the Palbreast Study
RECRUITINGRenal and Vascular Phenotypic Characterization of Patients With Enamel Renal Syndrome Due to a Pathogenic Variant of the FAM20A Gene and Pathophysiological Study of Ectopic Calcifications
NOT YET RECRUITINGExternal Resources
Links to major genomics databases and tools