EFEMP2

Chr 11AR

EGF-like fibulin extracellular matrix protein 2

Also known as: ARCL1B, FBLN4, MBP1, UPH1

A large number of extracellular matrix proteins have been found to contain variations of the epidermal growth factor (EGF) domain and have been implicated in functions as diverse as blood coagulation, activation of complement and determination of cell fate during development. The protein encoded by this gene contains four EGF2 domains and six calcium-binding EGF2 domains. This gene is necessary for elastic fiber formation and connective tissue development. Defects in this gene are cause of an autosomal recessive cutis laxa syndrome. Alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Jan 2011]

OMIMResearchGenerating clinical summary…
LOFmechanismARLOEUF 0.601 OMIM phenotype
Clinical SummaryEFEMP2
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Gene-Disease Validity (ClinGen)
cutis laxa, autosomal recessive, type 1B · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.60LOEUF
pLI 0.008
Z-score 3.03
OE 0.33 (0.200.60)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
0.98Z-score
OE missense 0.84 (0.750.93)
236 obs / 282.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.33 (0.200.60)
00.351.4
Missense OE?0.84 (0.750.93)
00.61.4
Synonymous OE?1.20
01.21.6
LoF obs/exp: 8 / 24.0Missense obs/exp: 236 / 282.1Syn Z: -1.70
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveEFEMP2-related cutis laxaLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7036th %ile
GOF
0.6444th %ile
LOF
0.3260th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

EFEMP2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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