EDIL3

Chr 5

EGF like and discoidin domains 3

Also known as: DEL1

NCBI Gene: 10085 ENSG00000164176 UniProt: O43854 OMIM: 606018

The protein promotes endothelial cell adhesion through interaction with the alpha-v/beta-3 integrin receptor and regulates vascular morphogenesis during embryonic development. Mutations cause developmental and epileptic encephalopathy with microcephaly and simplified gyral pattern, inherited in an autosomal recessive pattern. This gene is highly constrained against loss-of-function variants, suggesting such mutations have severe consequences.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is an integrin ligand. It plays an important role in mediating angiogenesis and may be important in vessel wall remodeling and development. It also influences endothelial cell behavior. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.63

Clinical Summary— EDIL3

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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

70 VUS of 92 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.63LOEUF

pLI 0.000

Z-score 3.14

OE 0.39 (0.25–0.63)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.16Z-score

OE missense 0.80 (0.71–0.89)

206 obs / 258.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.39 (0.25–0.63)

0≤0.351.4

Missense OE?0.80 (0.71–0.89)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 12 / 30.8Missense obs/exp: 206 / 258.7Syn Z: 0.48

This gene — mechanism propensity

0.75top 25%

GOF

0.72top 25%

LOF

0.2680th %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

92 submitted variants in ClinVar

ClinVar

Classification Summary

VUS70

Likely Benign5

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	70	0	70
Likely Benign	4	1	5
Benign	1	1	2
Total	75	2	77

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

View in ClinVar →

8 pathogenic / likely-pathogenic (of 17) ClinVar copy-number / structural variants overlap EDIL3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →