MMP3

Chr 11

matrix metallopeptidase 3

Also known as: CHDS6, MMP-3, SL-1, STMY, STMY1, STR1

NCBI Gene: 4314 ENSG00000149968 UniProt: P08254 OMIM: 185250

Proteins of the matrix metalloproteinase (MMP) 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. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. This gene encodes an enzyme which degrades fibronectin, laminin, collagens III, IV, IX, and X, and cartilage proteoglycans. The enzyme is thought to be involved in wound repair, progression of atherosclerosis, and tumor initiation. The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3. [provided by RefSeq, Jul 2008]

OMIM Research

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Coronary heart disease, susceptibility to, 6}MIM #614466

Active trials

514

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.42

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.42LOEUF

pLI 0.000

Z-score 0.03

OE 0.99 (0.71–1.42)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.64Z-score

OE missense 1.11 (1.01–1.23)

285 obs / 256.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.99 (0.71–1.42)

0≤0.351.4

Missense OE?1.11 (1.01–1.23)

0≤0.61.4

Synonymous OE?1.18

0≤1.21.6

LoF obs/exp: 22 / 22.2Missense obs/exp: 285 / 256.0Syn Z: -1.38

Background carrier burden — how many people carry a rare variant somewhere in MMP3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 73

596 rare PASS variants

Rare truncating (LoF)

1 in 590

114 rare PASS variants

Rare synonymous (reference)

1 in 150

232 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MMP3. 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 110	1 in 840
South Asian	~43k	1 in 67	1 in 210
Remaining (unassigned)	~30k	1 in 70	1 in 680
European (Finnish)	~27k	1 in 450	1 in 620
Admixed American	~22k	1 in 66	1 in 300
African / African American	~21k	1 in 58	1 in 280
East Asian	~20k	1 in 170	1 in 320
Ashkenazi Jewish	~13k	1 in 570	1 in 690
Middle Eastern	~2,884	1 in 93	1 in 580

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 10 of 10 coding exons well covered in gnomAD exomes. Genomes: 9 of 10 (exon 3 below).? see exons ↓