EMILIN1

Chr 2ARAD

elastin microfibril interfacer 1

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

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismAR/ADLOEUF 0.512 OMIM phenotypes
Clinical SummaryEMILIN1
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Gene-Disease Validity (ClinGen)
arterial tortuosity-bone fragility syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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
22 unique Pathogenic / Likely Pathogenic· 203 VUS of 266 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.51LOEUF
pLI 0.004
Z-score 3.82
OE 0.31 (0.190.51)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.21Z-score
OE missense 0.86 (0.800.93)
526 obs / 610.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.31 (0.190.51)
00.351.4
Missense OE0.86 (0.800.93)
00.61.4
Synonymous OE0.91
01.21.6
LoF obs/exp: 11 / 35.6Missense obs/exp: 526 / 610.3Syn Z: 1.12
DN
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

266 submitted variants in ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic2
VUS203
Likely Benign15
Benign10
Conflicting5
20
Pathogenic
2
Likely Pathogenic
203
VUS
15
Likely Benign
10
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
1
14
0
20
Likely Pathogenic
1
0
1
0
2
VUS
0
195
8
0
203
Likely Benign
0
8
3
4
15
Benign
0
5
2
3
10
Conflicting
5
Total6209287255

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

View in ClinVar →

Protein Context — Lollipop Plot

EMILIN1 · 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.

Search ClinicalTrials.gov →
Clinical Literature
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