EPB41L4B

Chr 9

erythrocyte membrane protein band 4.1 like 4B

Also known as: CG1, EHM2, LULU2

NCBI Gene: 54566ENSG00000095203UniProt: Q9H329

The protein serves as a structural constituent of the cytoskeleton and up-regulates the Rho guanine nucleotide exchange factor ARHGEF18, regulating the circumferential actomyosin belt in epithelial cells and promoting cellular adhesion and migration. Loss-of-function mutations in EPB41L4B cause neurodevelopmental disorders with an autosomal recessive inheritance pattern. The pathogenic mechanism involves disruption of cytoskeletal organization and cell adhesion processes critical for normal neural development.

Summary from RefSeq, UniProt, Mechanism
Research Assistant →
0
Active trials
1
Pubs (1 yr)
35
P/LP submissions
0%
P/LP missense
0.24
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical Summary— EPB41L4B
⚡
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.
📋
ClinVar Variants
35 unique Pathogenic / Likely Pathogenic· 112 VUS of 172 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.24LOEUF
pLI 1.000
Z-score 5.76
OE 0.12 (0.07–0.24)
Highly constrained

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

Missense Constraint
1.25Z-score
OE missense 0.84 (0.77–0.91)
395 obs / 471.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.12 (0.07–0.24)
0≤0.351.4
Missense OE0.84 (0.77–0.91)
0≤0.61.4
Synonymous OE0.88
0≤1.21.6
LoF obs/exp: 6 / 49.9Missense obs/exp: 395 / 471.4Syn Z: 1.26
DN
0.5673th %ile
GOF
0.6150th %ile
LOF
0.65top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.24

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

172 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic30
Likely Pathogenic5
VUS112
Likely Benign2
Conflicting1
30
Pathogenic
5
Likely Pathogenic
112
VUS
2
Likely Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
30
0
30
Likely Pathogenic
0
0
5
0
5
VUS
1
106
5
0
112
Likely Benign
0
1
0
1
2
Benign
0
0
0
0
0
Conflicting
—1
Total1107401150

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

View in ClinVar →

Protein Context — Lollipop Plot

EPB41L4B · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Prognostic Value and Immune Signatures of Anoikis-related Genes in Breast Cancer.
Wu Q et al.·J Immunother
2024
MicroRNAs Deregulated in Intraductal Papillary Mucinous Neoplasm Converge on Actin Cytoskeleton-Related Pathways That Are Maintained in Pancreatic Ductal Adenocarcinoma
Fernandez-Castañer E et al.·Cancers (Basel)
2021
Epigenetic modifications appear in the human placenta following anxiety and depression during pregnancy.
Martinez CA et al.·Placenta
2023
Identification of a 12-Gene Signature and Hub Genes Involved in Kidney Wilms Tumor via Integrated Bioinformatics Analysis
Huang G et al.·Front Oncol
2022
Overlapping Interstitial Deletions of the Region 9q22.33 to 9q33.3 of Three Patients Allow Pinpointing Candidate Genes for Epilepsy and Cleft Lip and Palate
Szalai R et al.·Mol Syndromol
2023Cohort
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 4 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients