EPB41L4A

Chr 5

erythrocyte membrane protein band 4.1 like 4A

Also known as: EPB41L4, NBL4

The protein encoded by this gene is a member of the band 4.1 protein superfamily. Members of this superfamily are thought to play an important role in regulating interactions between the cytoskeleton and plasma membrane, and contain an amino terminal conserved domain that binds glycophorin C. This gene product is thought to be involved in the beta-catenin signaling pathway. [provided by RefSeq, Dec 2016]

ResearchGenerating clinical summary…
MultiplemechanismLOEUF 1.01
Clinical SummaryEPB41L4A
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.01LOEUF
pLI 0.000
Z-score 1.46
OE 0.77 (0.601.01)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
-1.26Z-score
OE missense 1.18 (1.091.28)
451 obs / 381.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.77 (0.601.01)
00.351.4
Missense OE?1.18 (1.091.28)
00.61.4
Synonymous OE?1.17
01.21.6
LoF obs/exp: 38 / 49.1Missense obs/exp: 451 / 381.6Syn Z: -1.54

This gene — mechanism propensity

DN
0.6648th %ile
GOF
0.6639th %ile
LOF
0.4332th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

EPB41L4A · 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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