EPB42

erythrocyte membrane protein band 4.2, the group of Transglutaminases

Basic information

Region (hg38): 15:43197226-43221018

Links

ENSG00000166947 ∙ NCBI:2038 ∙ OMIM:177070 ∙ HGNC:3381 ∙ Uniprot:P16452 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary spherocytosis type 5 (Strong), mode of inheritance: AR
• hereditary spherocytosis (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spherocytosis, type 5	AR	Hematologic	Due to anemia, individuals may require transfusions and/or splenectomy	Hematologic	4830746; 4413274; 2963832; 2386772; 2139792; 1558976; 7803799; 7772513; 9734643; 10406914; 12176912; 14636652; 19269200; 21275958

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EPB42 gene.

• Hereditary spherocytosis type 5 (93 variants)
• not provided (87 variants)
• Inborn genetic diseases (28 variants)
• not specified (14 variants)
• Spherocytosis, Recessive (3 variants)
• EPB42-related condition (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EPB42 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			4	13	1	18
missense	1	3	66	2		72
nonsense	1					1
start loss			1			1
frameshift	1	3	1			5
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			5	3	1	9
non coding			5	4	17	26
Total	3	6	78	19	18

Highest pathogenic variant AF is 0.0000131

Variants in EPB42

This is a list of pathogenic ClinVar variants found in the EPB42 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-43197281-A-T		Hereditary spherocytosis type 5	Uncertain significance (Jan 13, 2018)
15-43197316-C-T		Inborn genetic diseases	Uncertain significance (Dec 12, 2023)
15-43197329-G-A			Likely benign (Jan 16, 2022)
15-43197334-C-T		Hereditary spherocytosis type 5 • EPB42-related disorder	Conflicting classifications of pathogenicity (Jan 29, 2024)
15-43197346-T-C		Hereditary spherocytosis type 5 • EPB42-related disorder • Inborn genetic diseases	Conflicting classifications of pathogenicity (Nov 30, 2023)
15-43197364-T-C		Inborn genetic diseases	Uncertain significance (Nov 17, 2022)
15-43197390-C-T		Inborn genetic diseases	Uncertain significance (Jun 24, 2022)
15-43197414-G-A		Hereditary spherocytosis type 5	Uncertain significance (Jul 25, 2022)
15-43197434-CATG-C		Spherocytosis, Recessive	Uncertain significance (Jun 14, 2016)
15-43197459-C-T			Uncertain significance (May 03, 2017)
15-43197483-C-A			Likely benign (Jan 12, 2024)
15-43197599-TG-T			Benign (Jun 20, 2021)
15-43201845-T-C		EPB42-related disorder	Likely benign (Apr 05, 2023)
15-43201869-GC-G		Hereditary spherocytosis type 5	Likely pathogenic (Sep 08, 2023)
15-43201881-G-A			Likely benign (Jan 14, 2022)
15-43201895-C-A		Inborn genetic diseases	Uncertain significance (Jun 07, 2023)
15-43201905-T-A		Hereditary spherocytosis type 5	Uncertain significance (Mar 10, 2023)
15-43201962-C-T		Hereditary spherocytosis type 5	Uncertain significance (Aug 13, 2021)
15-43201969-C-A		Inborn genetic diseases	Uncertain significance (Dec 17, 2023)
15-43201975-C-T		Hereditary spherocytosis type 5	Uncertain significance (Aug 02, 2023)
15-43202091-ACT-A			Benign (Nov 11, 2018)
15-43202924-G-T			Benign (Nov 11, 2018)
15-43203014-T-C			Benign (Nov 11, 2018)
15-43203108-T-C		Hereditary spherocytosis type 5	Likely benign (May 06, 2021)
15-43203127-G-T		Hereditary spherocytosis type 5	Conflicting classifications of pathogenicity (Jan 25, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EPB42	protein_coding	protein_coding	ENST00000300215	13	115059

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.90e-9	0.996	125689	0	59	125748	0.000235

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.939	348	401	0.868	0.0000241	4669
Missense in Polyphen		89	122.81	0.7247		1552
Synonymous	0.669	151	162	0.933	0.00000980	1484
Loss of Function	2.63	19	36.1	0.527	0.00000202	391

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000487	0.000485
Ashkenazi Jewish	0.00	0.00
East Asian	0.000489	0.000489
Finnish	0.000323	0.000323
European (Non-Finnish)	0.000185	0.000185
Middle Eastern	0.000489	0.000489
South Asian	0.000327	0.000327
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probably plays an important role in the regulation of erythrocyte shape and mechanical properties.
• Disease: DISEASE: Spherocytosis 5 (SPH5) [MIM:612690]: Spherocytosis is a hematologic disorder leading to chronic hemolytic anemia and characterized by numerous abnormally shaped erythrocytes which are generally spheroidal. Absence of band 4.2 associated with spur or target erythrocytes has also been reported. {ECO:0000269|PubMed:10406914, ECO:0000269|PubMed:1558976, ECO:0000269|PubMed:7772513, ECO:0000269|PubMed:7819064, ECO:0000269|PubMed:8547071, ECO:0000269|PubMed:8547605}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.127

Intolerance Scores

• loftool: 0.299
• rvis_EVS: -0.19
• rvis_percentile_EVS: 39.24

Haploinsufficiency Scores

• pHI: 0.410
• hipred: N
• hipred_score: 0.145
• ghis: 0.533

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.281

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Epb42
• Phenotype: immune system phenotype; homeostasis/metabolism phenotype; hematopoietic system phenotype

Gene ontology

• Biological process: cell morphogenesis;cytoskeleton organization;regulation of cell shape;peptide cross-linking;hemoglobin metabolic process;erythrocyte maturation;spleen development;iron ion homeostasis
• Cellular component: cytoskeleton;plasma membrane;cortical cytoskeleton
• Molecular function: protein-glutamine gamma-glutamyltransferase activity;structural constituent of cytoskeleton;protein binding;ATP binding