MMP14

Chr 14

matrix metallopeptidase 14

Also known as: MMP-14, MMP-X1, MT-MMP, MT-MMP 1, MT1-MMP, MT1MMP, MTMMP1, WNCHRS

NCBI Gene: 4323 ENSG00000157227 UniProt: P50281

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. However, the protein encoded by this gene is a member of the membrane-type MMP (MT-MMP) subfamily; each member of this subfamily contains a potential transmembrane domain suggesting that these proteins are expressed at the cell surface rather than secreted. This protein activates MMP2 protein, and this activity may be involved in tumor invasion. [provided by RefSeq, Jul 2008]

Research

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtWinchester syndrome

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

163

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.27

LOEUF· LoF intol.

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.27LOEUF

pLI 0.995

Z-score 4.48

OE 0.10 (0.05–0.27)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

1.48Z-score

OE missense 0.78 (0.71–0.86)

290 obs / 370.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.10 (0.05–0.27)

0≤0.351.4

Missense OE?0.78 (0.71–0.86)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 3 / 29.1Missense obs/exp: 290 / 370.4Syn Z: 0.24

Background carrier burden — how many people carry a rare variant somewhere in MMP14?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 57

662 rare PASS variants

Rare truncating (LoF)

1 in 3,500

36 rare PASS variants

Rare synonymous (reference)

1 in 140

347 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MMP14. 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 74	1 in 9,200
South Asian	~43k	1 in 67	1 in 4,300
Remaining (unassigned)	~30k	1 in 59	≈ 1 in 7,500
European (Finnish)	~27k	1 in 440	none seen
Admixed American	~22k	1 in 100	≈ 1 in 8,600
African / African American	~21k	1 in 88	≈ 1 in 5,600
East Asian	~20k	1 in 85	1 in 520
Ashkenazi Jewish	~13k	1 in 520	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 95	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): All 10 coding exons well covered in gnomAD exomes and genomes.? see exons ↓