ECM1

Chr 1AR

extracellular matrix protein 1

Also known as: URBWD

ECM1 encodes a soluble extracellular protein that regulates bone mineralization, promotes angiogenesis by stimulating endothelial cell proliferation, and inhibits MMP9 proteolytic activity. Biallelic mutations cause Urbach-Wiethe disease (lipoid proteinosis), an autosomal recessive disorder characterized by generalized thickening of skin, mucosae, and certain viscera. The gene shows tolerance to loss-of-function variants (pLI near zero), consistent with its recessive inheritance pattern.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.131 OMIM phenotype
Clinical SummaryECM1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
44 unique Pathogenic / Likely Pathogenic· 98 VUS of 208 total submissions
📖
GeneReview available — ECM1
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.13LOEUF
pLI 0.000
Z-score 1.01
OE 0.80 (0.581.13)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.22Z-score
OE missense 1.03 (0.951.13)
336 obs / 324.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.80 (0.581.13)
00.351.4
Missense OE1.03 (0.951.13)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 24 / 30.0Missense obs/exp: 336 / 324.6Syn Z: 0.09

ClinVar Variant Classifications

208 submitted variants in ClinVar

Classification Summary

Pathogenic32
Likely Pathogenic12
VUS98
Likely Benign24
Benign28
Conflicting1
32
Pathogenic
12
Likely Pathogenic
98
VUS
24
Likely Benign
28
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
22
0
10
0
32
Likely Pathogenic
8
3
1
0
12
VUS
1
91
6
0
98
Likely Benign
0
7
6
11
24
Benign
0
6
18
4
28
Conflicting
1
Total311074115195

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ECM1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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