MGP

Chr 12AR

matrix Gla protein

Also known as: GIG36, MGLAP, NTI

NCBI Gene: 4256 ENSG00000111341 UniProt: P08493 OMIM: 154870

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Keutel syndromeMIM #245150

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · Keutel syndrome · AR · ClinGen 2025

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

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

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LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

gnomad: Error: gnomAD API error: 400

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 220

213 rare PASS variants

Rare truncating (LoF)

1 in 1,500

43 rare PASS variants

Rare synonymous (reference)

1 in 1,700

49 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MGP. 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 200	1 in 1,400
South Asian	~43k	1 in 340	≈ 1 in 11,000
Remaining (unassigned)	~30k	1 in 280	1 in 1,600
European (Finnish)	~27k	1 in 1,900	1 in 4,800
Admixed American	~22k	1 in 240	1 in 1,900
African / African American	~21k	1 in 75	1 in 2,500
East Asian	~20k	1 in 670	1 in 2,400
Ashkenazi Jewish	~13k	1 in 390	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 210	≈ 1 in 2,800

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): 3 of 4 coding exons well covered in gnomAD exomes; exon 2 marginal. Genomes: all 4.? see exons ↓