EPB42

erythrocyte membrane protein band 4.2, the group of Transglutaminases

Basic information

Region (hg38): 15:43197227-43221018

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 (137 variants)
not_provided (99 variants)
Inborn_genetic_diseases (89 variants)
not_specified (14 variants)
EPB42-related_disorder (9 variants)
Spherocytosis,_Recessive (3 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. These statistics are base on transcript: NM_001114134.2. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	25 clinvar	2 clinvar	31
missense	1 clinvar	5 clinvar	140 clinvar	19 clinvar		165
nonsense	2 clinvar	1 clinvar				3
start loss			1			1
frameshift	3 clinvar	7 clinvar	1 clinvar			11
splice donor/acceptor (+/-2bp)	1 clinvar					1
Total	7	13	146	44	2

Highest pathogenic variant AF is 0.00008920728

Loading clinvar variants...

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