EMILIN1

Chr 2

elastin microfibril interfacer 1

Also known as: ATBFS, EMI, EMILIN, HMN10, HMND10, gp115

NCBI Gene: 11117 ENSG00000138080 UniProt: Q9Y6C2

The protein is involved in elastic and collagen fiber formation in the extracellular matrix and is required for collagen network assembly and cross-linking, particularly at the interface between elastin and microfibrils in blood vessels, skin, heart and lung. Mutations cause arterial tortuosity-bone fragility syndrome (autosomal recessive) and distal hereditary motor neuronopathy type 10 (autosomal dominant). The gene shows moderate constraint against loss-of-function variants, reflecting its importance in connective tissue and vascular development.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes an extracellular matrix glycoprotein that is characterized by an N-terminal microfibril interface domain, a coiled-coiled alpha-helical domain, a collagenous domain and a C-terminal globular C1q domain. The encoded protein associates with elastic fibers at the interface between elastin and microfibrils and may play a role in the development of elastic tissues including large blood vessels, dermis, heart and lung. [provided by RefSeq, Sep 2009]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.51

Clinical Summary— EMILIN1

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Gene-Disease Validity (ClinGen)

arterial tortuosity-bone fragility syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.

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ClinVar Variants

7 unique Pathogenic / Likely Pathogenic· 196 VUS of 243 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.51LOEUF

pLI 0.004

Z-score 3.82

OE 0.31 (0.19–0.51)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.21Z-score

OE missense 0.86 (0.80–0.93)

526 obs / 610.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.31 (0.19–0.51)

0≤0.351.4

Missense OE?0.86 (0.80–0.93)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 11 / 35.6Missense obs/exp: 526 / 610.3Syn Z: 1.12

This gene — mechanism propensity

0.6840th %ile

GOF

0.6736th %ile

LOF

0.3260th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

243 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6

Likely Pathogenic1

VUS196

Likely Benign15

Benign9

Conflicting5

Pathogenic

Likely Pathogenic

196

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	5	1	0	0	6
Likely Pathogenic	1	0	0	0	1
VUS	0	195	1	0	196
Likely Benign	0	8	3	4	15
Benign	0	5	1	3	9
Conflicting	—				5
Total	6	209	5	7	232

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

View in ClinVar →

15 pathogenic / likely-pathogenic (of 23) ClinVar copy-number / structural variants overlap EMILIN1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →