EPB41

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

Basic information

Region (hg38): 1:28887091-29120046

Previous symbols: [ "EL1" ]

Links

ENSG00000159023 ∙ NCBI:2035 ∙ OMIM:130500 ∙ HGNC:3377 ∙ Uniprot:P11171 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary elliptocytosis (Supportive), mode of inheritance: AD
• elliptocytosis 1 (Strong), mode of inheritance: AD
• elliptocytosis 1 (Definitive), mode of inheritance: Semidominant
• elliptocytosis 1 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ellipsocytosis 1	AR	Hematologic	The recessive form is more severe, and due to anemia, individuals may require transfusions, and/or splenectomy	Hematologic	5731934; 7255153; 6894932; 7082842; 3965051; 3995181; 3755799; 3748797; 3674005; 1430200; 16730867; 14692233; 21839655

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EPB41 gene.

• Elliptocytosis_1 (102 variants)
• not_provided (99 variants)
• Inborn_genetic_diseases (52 variants)
• EPB41-related_disorder (13 variants)
• not_specified (5 variants)
• Hereditary_elliptocytosis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EPB41 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001376013.1. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	20	2	27
missense	2	2	124	12	1	141
nonsense	5	9				14
start loss						0
frameshift	4	7	1			12
splice donor/acceptor (+/-2bp)		3				3
Total	11	21	130	32	3

Highest pathogenic variant AF is 0.0000193416

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EPB41	protein_coding	protein_coding	ENST00000343067	19	232951

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000359	1.00	125695	0	53	125748	0.000211

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.922	406	462	0.879	0.0000252	5670
Missense in Polyphen		210	267.85	0.78402		3173
Synonymous	0.276	160	165	0.973	0.00000926	1625
Loss of Function	4.25	17	49.1	0.346	0.00000263	602

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000474	0.000474
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000217
Finnish	0.000323	0.000323
European (Non-Finnish)	0.000167	0.000167
Middle Eastern	0.000218	0.000217
South Asian	0.000261	0.000261
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Protein 4.1 is a major structural element of the erythrocyte membrane skeleton. It plays a key role in regulating membrane physical properties of mechanical stability and deformability by stabilizing spectrin-actin interaction. Recruits DLG1 to membranes. Required for dynein-dynactin complex and NUMA1 recruitment at the mitotic cell cortex during anaphase (PubMed:23870127). {ECO:0000269|PubMed:23870127}.
• Disease: DISEASE: Elliptocytosis 1 (EL1) [MIM:611804]: A Rhesus-linked form of hereditary elliptocytosis, a genetically heterogeneous, autosomal dominant hematologic disorder. It is characterized by variable hemolytic anemia and elliptical or oval red cell shape. {ECO:0000269|PubMed:3467321}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Splicing factor NOVA regulated synaptic proteins;Neuronal System;Neurexins and neuroligins;Protein-protein interactions at synapses;Syndecan-2-mediated signaling events (Consensus)

Recessive Scores

• pRec: 0.359

Intolerance Scores

• loftool: 0.0367
• rvis_EVS: -0.6
• rvis_percentile_EVS: 18.19

Haploinsufficiency Scores

• pHI: 0.757
• hipred: Y
• hipred_score: 0.744
• ghis: 0.494

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.945

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Epb41
• Phenotype: renal/urinary system phenotype; immune system phenotype; liver/biliary system phenotype; hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: epb41b
• Affected structure: nucleate erythrocyte
• Phenotype tag: abnormal
• Phenotype quality: increased fragility

Gene ontology

• Biological process: cell cycle;regulation of cell shape;actin cytoskeleton organization;cortical actin cytoskeleton organization;actomyosin structure organization;positive regulation of protein binding;cell division;protein-containing complex assembly;positive regulation of protein localization to cell cortex
• Cellular component: nucleus;cytosol;plasma membrane;cytoplasmic side of plasma membrane;postsynaptic density;spectrin-associated cytoskeleton;cell junction;cortical cytoskeleton;protein-containing complex;cell cortex region
• Molecular function: actin binding;structural constituent of cytoskeleton;protein binding;calmodulin binding;1-phosphatidylinositol binding;protein C-terminus binding;spectrin binding;protein N-terminus binding;phosphoprotein binding