EPB41L1

erythrocyte membrane protein band 4.1 like 1, the group of Erythrocyte membrane protein band 4.1|FERM domain containing

Basic information

Region (hg38): 20:36091503-36232799

Links

ENSG00000088367 ∙ NCBI:2036 ∙ OMIM:602879 ∙ HGNC:3378 ∙ Uniprot:Q9H4G0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal dominant 40 (Limited), mode of inheritance: AD
• autosomal dominant non-syndromic intellectual disability (Supportive), mode of inheritance: AD
• complex neurodevelopmental disorder (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mental retardation, autosomal dominant 11	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	21376300

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EPB41L1 gene.

• not provided (47 variants)
• not specified (32 variants)
• Inborn genetic diseases (29 variants)
• Intellectual disability, autosomal dominant 11 (8 variants)
• Abnormal brain morphology (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EPB41L1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	21	6	29
missense		1	33	11	2	47
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				5	1	6
non coding			2	1	4	7
Total	0	1	38	33	12

Variants in EPB41L1

This is a list of pathogenic ClinVar variants found in the EPB41L1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
20-36125460-G-A		Intellectual disability, autosomal dominant 11	Uncertain significance (May 21, 2020)
20-36125528-G-A		Intellectual disability, autosomal dominant 11	Uncertain significance (Dec 17, 2022)
20-36173799-G-A		not specified	Uncertain significance (Jan 31, 2022)
20-36173834-G-A		not specified	Uncertain significance (Sep 17, 2014)
20-36173888-C-T		not specified	Benign/Likely benign (Mar 01, 2022)
20-36173889-G-A		EPB41L1-related disorder • not specified	Conflicting classifications of pathogenicity (Mar 28, 2023)
20-36173900-G-T		not specified	Uncertain significance (Jul 25, 2023)
20-36173906-C-G		not specified	Uncertain significance (Aug 26, 2022)
20-36173907-T-C		Intellectual disability, autosomal dominant 11	Uncertain significance (Feb 23, 2021)
20-36173910-A-G		not specified	Uncertain significance (Aug 04, 2023)
20-36173938-C-T		not specified	Uncertain significance (Feb 11, 2022)
20-36175561-T-C		not specified	Uncertain significance (Jan 17, 2024)
20-36175570-A-G		not specified	Uncertain significance (Dec 01, 2022)
20-36175586-C-T			Likely benign (Dec 01, 2022)
20-36175597-C-T		not specified	Likely benign (Mar 04, 2016)
20-36175613-C-A			Likely benign (Apr 01, 2022)
20-36175692-T-G		not specified	Likely benign (Aug 14, 2014)
20-36177946-C-T		not specified	Likely benign (Sep 26, 2019)
20-36177962-G-A		not specified	Uncertain significance (Dec 21, 2022)
20-36177981-C-T			Likely benign (Jul 04, 2018)
20-36178023-C-T			Likely benign (Jan 01, 2023)
20-36182312-G-T		not specified	Benign/Likely benign (Sep 01, 2023)
20-36182336-A-G		not specified	Benign (Dec 31, 2019)
20-36182354-G-A			Likely benign (Jun 20, 2018)
20-36182355-C-T			Likely benign (Dec 28, 2017)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EPB41L1	protein_coding	protein_coding	ENST00000338074	21	141296

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.877	0.123	125731	0	17	125748	0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.94	394	518	0.760	0.0000337	5781
Missense in Polyphen		116	216.23	0.53647		2487
Synonymous	1.73	183	215	0.850	0.0000143	1743
Loss of Function	4.87	8	42.1	0.190	0.00000207	516

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000621	0.0000615
Ashkenazi Jewish	0.000103	0.0000992
East Asian	0.000273	0.000272
Finnish	0.0000465	0.0000462
European (Non-Finnish)	0.0000793	0.0000791
Middle Eastern	0.000273	0.000272
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May function to confer stability and plasticity to neuronal membrane via multiple interactions, including the spectrin-actin-based cytoskeleton, integral membrane channels and membrane-associated guanylate kinases.
• Pathway: Splicing factor NOVA regulated synaptic proteins;Neuronal System;Neurexins and neuroligins;Trafficking of AMPA receptors;Glutamate binding, activation of AMPA receptors and synaptic plasticity;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses;Protein-protein interactions at synapses;Trk receptor signaling mediated by PI3K and PLC-gamma (Consensus)

Recessive Scores

• pRec: 0.0936

Intolerance Scores

• loftool: 0.0449
• rvis_EVS: -0.73
• rvis_percentile_EVS: 14.15

Haploinsufficiency Scores

• pHI: 0.113
• hipred: Y
• hipred_score: 0.563
• ghis: 0.568

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.839

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Epb41l1
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); normal phenotype

Gene ontology

• Biological process: cortical actin cytoskeleton organization;actomyosin structure organization
• Cellular component: cytosol;cytoskeleton;plasma membrane
• Molecular function: actin binding;structural molecule activity;protein binding