MMP13

Chr 11ADAR

matrix metallopeptidase 13

Also known as: CLG3, MANDP1, MDST, MMP-13

NCBI Gene: 4322 ENSG00000137745 UniProt: P45452 OMIM: 600108

This gene encodes a member of the peptidase M10 family of matrix metalloproteinases (MMPs). Proteins in this family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. The encoded preproprotein is proteolytically processed to generate the mature protease. This protease cleaves type II collagen more efficiently than types I and III. It may be involved in articular cartilage turnover and cartilage pathophysiology associated with osteoarthritis. Mutations in this gene are associated with metaphyseal anadysplasia. This gene is part of a cluster of MMP genes on chromosome 11. [provided by RefSeq, Jan 2016]

GeneReviews OMIM Research

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Spondyloepimetaphyseal dysplasia, Missouri typeMIM #602111

Metaphyseal anadysplasia 1MIM #602111

Metaphyseal dysplasia, Spahr typeMIM #250400

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Metaphyseal anadysplasia 1; Metaphyseal dysplasia, Spahr type; no ClinGen or GenCC tier

Active trials

558

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.52

LOEUF

Multiple*

Mechanism· predicted

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GeneReview available — MMP13

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.52LOEUF

pLI 0.000

Z-score -0.41

OE 1.09 (0.80–1.52)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.21Z-score

OE missense 1.04 (0.94–1.15)

268 obs / 258.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.09 (0.80–1.52)

0≤0.351.4

Missense OE?1.04 (0.94–1.15)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 25 / 22.9Missense obs/exp: 268 / 258.5Syn Z: -0.11

Background carrier burden — how many people carry a rare variant somewhere in MMP13?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 71

659 rare PASS variants

Rare truncating (LoF)

1 in 1,100

116 rare PASS variants

Rare synonymous (reference)

1 in 160

222 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MMP13. 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 92	1 in 1,300
South Asian	~43k	1 in 94	1 in 580
Remaining (unassigned)	~30k	1 in 59	1 in 1,900
European (Finnish)	~27k	1 in 290	1 in 5,300
Admixed American	~22k	1 in 70	1 in 1,100
African / African American	~21k	1 in 74	1 in 730
East Asian	~20k	1 in 61	1 in 2,500
Ashkenazi Jewish	~13k	1 in 240	≈ 1 in 3,400
Middle Eastern	~2,884	1 in 89	none seen

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): 9 of 10 coding exons well covered in gnomAD exomes; exon 9 marginal. Genomes: all 10.? see exons ↓