EFEMP1

Chr 2ARAD

EGF-like fibulin extracellular matrix protein 1

Also known as: ARCL1D, DHRD, DRAD, FBLN3, FBNL, FIBL-3, GLC1H, MLVT

This gene encodes fibulin-4, an extracellular matrix glycoprotein that binds the EGF receptor and regulates cell adhesion, migration, and glial cell functions in neural development. Mutations cause Doyne honeycomb retinal dystrophy and open-angle glaucoma (autosomal dominant) as well as autosomal recessive cutis laxa with connective tissue abnormalities. The gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely incompatible with normal development.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismAR/ADLOEUF 0.153 OMIM phenotypes
Clinical SummaryEFEMP1
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Gene-Disease Validity (ClinGen)
Doyne honeycomb retinal dystrophy · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.15LOEUF
pLI 1.000
Z-score 4.99
OE 0.03 (0.010.15)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.82Z-score
OE missense 0.69 (0.610.78)
192 obs / 277.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.03 (0.010.15)
00.351.4
Missense OE0.69 (0.610.78)
00.61.4
Synonymous OE1.10
01.21.6
LoF obs/exp: 1 / 31.0Missense obs/exp: 192 / 277.5Syn Z: -0.83
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveEFEMP1-related Doyne honeycomb degeneration of retinaOTHERAD
DN
0.4983th %ile
GOF
0.4776th %ile
LOF
0.59top 25%

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

LOFLOEUF 0.15
GOF1 literature citation

Literature Evidence

GOFA recurrent gain-of-function variant (p.(Arg345Trp)) in EFEMP1 has previously been associated with Doyne honeycomb retinal dystrophy.PMID:33807164

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

EFEMP1 · 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.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗