EPB41L4A

Chr 5

erythrocyte membrane protein band 4.1 like 4A

Also known as: EPB41L4, NBL4

NCBI Gene: 64097ENSG00000129595UniProt: Q9HCS5

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]

175
ClinVar variants
28
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— EPB41L4A
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
28 Pathogenic / Likely Pathogenic· 126 VUS of 175 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.01LOEUF
pLI 0.000
Z-score 1.46
OE 0.77 (0.60–1.01)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-1.26Z-score
OE missense 1.18 (1.09–1.28)
451 obs / 381.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.77 (0.60–1.01)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.18 (1.09–1.28)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.17
0≤1.21.6
LoF obs/exp: 38 / 49.1Missense obs/exp: 451 / 381.6Syn Z: -1.54

ClinVar Variant Classifications

175 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic1
VUS126
Likely Benign15
Benign6
27
Pathogenic
1
Likely Pathogenic
126
VUS
15
Likely Benign
6
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
27
0
27
Likely Pathogenic
0
1
0
0
1
VUS
1
108
17
0
126
Likely Benign
0
8
3
4
15
Benign
0
3
1
2
6
Total1120486175

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

View 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Accelerating novel candidate gene discovery in neurogenetic disorders via whole-exome sequencing of prescreened multiplex consanguineous families.
Alazami AM et al.·Cell Rep
2015
IncRNA EPB41L4A-AS1 Mitigates the Proliferation of Non-Small-Cell Lung Cancer Cells through the miR-105-5p/GIMAP6 Axis.
Dong B et al.·Crit Rev Eukaryot Gene Expr
2023
Downregulation of lncRNA EPB41L4A-AS1 promotes gastric cancer cell proliferation, migration and invasion.
Ma J et al.·BMC Gastroenterol
2024
Persistent high glucose induced EPB41L4A-AS1 inhibits glucose uptake via GCN5 mediating crotonylation and acetylation of histones and non-histones.
Liao W et al.·Clin Transl Med
2022
Characterizing the function of EPB41L4A in the predisposition to papillary thyroid carcinoma.
Comiskey DF Jr et al.·Sci Rep
2020
The long non-coding RNA EPB41L4A-AS2 inhibits tumor proliferation and is associated with favorable prognoses in breast cancer and other solid tumors.
Xu S et al.·Oncotarget
2016
Long noncoding RNA EPB41L4A-AS2 inhibits hepatocellular carcinoma development by sponging miR-301a-5p and targeting FOXL1.
Wang YG et al.·J Exp Clin Cancer Res
2019
Age related gene DST represents an independent prognostic factor for MYCN non-amplified neuroblastoma.
Wang H et al.·BMC Pediatr
2021
Long non-coding RNA EPB41L4A-AS1 as a biomarker of sepsis alleviates inflammatory response by targeting miR-146a-5p.
Zhou W et al.·Eur J Med Res
2025
Structural variants in the Epb41l4a locus: TAD disruption and Nrep gene misregulation as hypothetical drivers of neurodevelopmental outcomes.
Salnikov P et al.·Sci Rep
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools