EPB41L3

protein-coding

erythrocyte membrane protein band 4.1 like 3, the group of Erythrocyte membrane protein band 4.1|FERM domain containing

Gene summary

Predicted to enable cytoskeletal protein-membrane anchor activity. Predicted to be a structural constituent of cytoskeleton. Predicted to be involved in several processes, including nervous system development; paranodal junction maintenance; and protein localization to juxtaparanode region of axon. Located in cell-cell junction and plasma membrane. Implicated in esophagus squamous cell carcinoma. Biomarker of meningioma. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_012307.5

Inheritance

ClinVar variants

U:159B:15

Top phenotype

neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities

gnomAD constraint

pLI —, LoF o/e 0.33

Max pathogenic AF

—

Genomic locus

chr18:5,392,381-5,630,700

External References & Databases

Ensembl (ENSG00000082397)

Transcript & Mutation Effects

hg38 • Region Span ~238.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0100038

Submitter: G2P

neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalitiesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030063

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to EPB41L3 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 152

not providedTotal: 15

EPB41L3-related conditionTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012307.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	2 clinvar	2 clinvar	7
missense			153 clinvar	7 clinvar	4 clinvar	164
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	159	9	6	174

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 182 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012307.5	RefSeq	NP_036439.2	21	MANE Select
ENST00000341928.7	Ensembl	ENSP00000343158.2	21	MANE Select
NM_001281533.2	RefSeq	NP_001268462.1	20	Standard
NM_001281534.3	RefSeq	NP_001268463.1	18	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Splicing factor NOVA regulated synaptic proteins
Neuronal System
Neurexins and neuroligins
Protein-protein interactions at synapses

Biological Process

regulation of cell growth
protein localization to paranode region of axon
apoptotic process
cytoskeletal anchoring at plasma membrane
biological_process

Molecular Function

actin binding
structural constituent of cytoskeleton
protein binding

Cellular Component

cytosol
cytoskeleton
plasma membrane
cell-cell junction
postsynaptic density

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000341928
Coding exons: 21
Length: 238317
Individuals with no LoFs: 125685
Homozygous LoFs: 0
Heterozygous LoFs: 63
Defined: 125748
p: 0.000251

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.48	534	639	0.835	0.0000383	7030
Missense (PolyPhen)		189	270.84	0.69782		3111
Synonymous	-0.516	283	272	1.04	0.0000183	2169
Loss of Function	4.78	19	58.5	0.325	0.00000320	688

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00033	0.00031	rare
Latino/Admixed American	0.00046	0.00046	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.00034	0.00032	rare
European (Non-Finnish)	0.00026	0.00025	rare
South Asian	0.00010	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Tumor suppressor that inhibits cell proliferation and promotes apoptosis. Modulates the activity of protein arginine N- methyltransferases, including PRMT3 and PRMT5. {ECO:0000269|PubMed:15334060, ECO:0000269|PubMed:15737618, ECO:0000269|PubMed:16420693, ECO:0000269|PubMed:9892180}.;

Recessive Scores

pRec: 0.204

Intolerance Scores

RVIS EVS: 0.9
RVIS percentile EVS: 89.33

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.645

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium