ECM1

Chr 1AR

extracellular matrix protein 1

Also known as: URBWD

NCBI Gene: 1893 ENSG00000143369 UniProt: Q16610 OMIM: 602201

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a soluble protein that is involved in endochondral bone formation, angiogenesis, and tumor biology. It also interacts with a variety of extracellular and structural proteins, contributing to the maintenance of skin integrity and homeostasis. Mutations in this gene are associated with lipoid proteinosis disorder (also known as hyalinosis cutis et mucosae or Urbach-Wiethe disease) that is characterized by generalized thickening of skin, mucosae and certain viscera. Alternatively spliced transcript variants encoding distinct isoforms have been described for this gene. [provided by RefSeq, Feb 2011]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.131 OMIM phenotype

Clinical Summary— ECM1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

14 unique Pathogenic / Likely Pathogenic· 67 VUS of 94 total submissions

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GeneReview available — ECM1

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?

1.13LOEUF

pLI 0.000

Z-score 1.01

OE 0.80 (0.58–1.13)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.22Z-score

OE missense 1.03 (0.95–1.13)

336 obs / 324.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.80 (0.58–1.13)

0≤0.351.4

Missense OE?1.03 (0.95–1.13)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 24 / 30.0Missense obs/exp: 336 / 324.6Syn Z: 0.09

ClinVar Variant Classifications

94 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10

Likely Pathogenic4

VUS67

Likely Benign4

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	10	0	10
Likely Pathogenic	3	1	4
VUS	0	67	67
Likely Benign	0	4	4
Benign	0	0	0
Total	13	72	85

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

View in ClinVar →

5 pathogenic / likely-pathogenic (of 6) ClinVar copy-number / structural variants overlap ECM1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →