ECM1

Chr 1AR

extracellular matrix protein 1

Also known as: URBWD

NCBI Gene: 1893ENSG00000143369UniProt: Q16610

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]

Primary Disease Associations & Inheritance

Urbach-Wiethe diseaseMIM #247100
AR
UniProtLipoid proteinosis
192
ClinVar variants
43
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ECM1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
43 Pathogenic / Likely Pathogenic· 96 VUS of 192 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.22Z-score
OE missense 1.03 (0.95–1.13)
336 obs / 324.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.80 (0.58–1.13)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.03 (0.95–1.13)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.99
0≤1.21.6
LoF obs/exp: 24 / 30.0Missense obs/exp: 336 / 324.6Syn Z: 0.09

ClinVar Variant Classifications

192 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic32
Likely Pathogenic11
VUS96
Likely Benign24
Benign28
Conflicting1
32
Pathogenic
11
Likely Pathogenic
96
VUS
24
Likely Benign
28
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
13
0
19
0
32
Likely Pathogenic
5
3
3
0
11
VUS
0
89
7
0
96
Likely Benign
0
7
6
11
24
Benign
0
6
18
4
28
Conflicting
—1
Total181055315192

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.

Gene2Phenotype Curations

ECM1-related lipoid proteinosis

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkin
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Urbach-Wiethe disease

MIM #247100

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — ECM1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
ECM1 is an essential factor for the determination of M1 macrophage polarization in IBD in response to LPS stimulation.
Zhang Y et al.·Proc Natl Acad Sci U S A
2020
Identification of prospective aging drug targets via Mendelian randomization analysis.
Mao R et al.·Aging Cell
2024
Lipoid proteinosis.
Mcgrath JA·Handb Clin Neurol
2015Review
Mechanistic study of celastrol-mediated inhibition of proinflammatory activation of macrophages in IgA nephropathy via down-regulating ECM1.
Zhao J et al.·Int J Biol Sci
2024
Organ-specific proteomic aging clocks predict disease and longevity across diverse populations.
Wang Y et al.·Nat Aging
2026
Alternative splicing in ovarian cancer.
Wei L et al.·Cell Commun Signal
2024Review
Augmenting antitumor efficacy of Th17-derived Th1 cells through IFN-γ-induced type I interferon response network via IRF7.
Lei X et al.·Proc Natl Acad Sci U S A
2024
Mechanisms Underlying Rare Inherited Pediatric Retinal Vascular Diseases: FEVR, Norrie Disease, Persistent Fetal Vascular Syndrome.
Le V et al.·Cells
2023Review
Lipoid proteinosis: Novel ECM1 pathogenic variants and intrafamilial variability in four unrelated Arab families.
Li M et al.·Pediatr Dermatol
2023
Genetics of ulcerative colitis.
Thompson AI et al.·Inflamm Bowel Dis
2011Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
The correlation between serum ECM1 and cardiac fibrosis in heart failure patients.
Xu Y et al.·BMC Cardiovasc Disord
2025🔓 Open AccessCohort
Opportunities and Risks of Promoting Skin and Bone Healing via Implant Biofunctionalization of Extracellular Matrix Protein ECM1.
Braun NR et al.·J Funct Biomater
2025🔓 Open AccessFunctional
Identification and validation of ECM1 as a causal plasma biomarker in knee osteoarthritis through proteome-wide association study and bioinformatics.
Wang H et al.·Medicine (Baltimore)
2025🔓 Open Access
ECM1 protects against liver steatosis through PCBP1-mediated iron homeostasis.
Zhang D et al.·Hepatology
2026
Human menstrual blood-derived stem cells secreted ECM1 directly interacts with LRP1α to ameliorate hepatic fibrosis through FoxO1 and mTOR signaling pathway.
Fang Y et al.·Stem Cell Res Ther
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools