EPB42 (erythrocyte membrane protein band 4.2)

Gene

• Entrez ID: 2038
• Gene name: Erythrocyte membrane protein band 4.2
• Gene symbol: EPB42
• Synonyms (NCBI Gene): PA, SPH5
• Chromosome: 15
• Chromosome location: 15q15.2
• Summary: Erythrocyte membrane protein band 4.2 is an ATP-binding protein which may regulate the association of protein 3 with ankyrin. It probably has a role in erythrocyte shape and mechanical property regulation. Mutations in the EPB42 gene are associated with r

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs115998465	C>A,G	Pathogenic	Missense variant, coding sequence variant, stop gained
rs121917734	C>T	Pathogenic	Missense variant, coding sequence variant
rs143682977	C>A,G	Pathogenic	Missense variant, coding sequence variant, 5 prime UTR variant
rs266257354	C>-	Pathogenic	Coding sequence variant, upstream transcript variant, genic upstream transcript variant, frameshift variant
rs266257355	C>T	Pathogenic	Splice donor variant
rs515726211	G>A	Pathogenic	Coding sequence variant, missense variant
rs515726212	G>A	Pathogenic	Coding sequence variant, missense variant
rs515726213	C>-	Pathogenic	Coding sequence variant, frameshift variant
rs768899304	G>A	Conflicting-interpretations-of-pathogenicity	Intron variant, synonymous variant, coding sequence variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000902	Process	Cell morphogenesis	IEA
GO:0003810	Function	Protein-glutamine gamma-glutamyltransferase activity	IBA
GO:0003810	Function	Protein-glutamine gamma-glutamyltransferase activity	IEA
GO:0005200	Function	Structural constituent of cytoskeleton	TAS	1350227
GO:0005515	Function	Protein binding	IPI	12646258, 12970870, 32814053
GO:0005524	Function	ATP binding	TAS	8608138
GO:0005737	Component	Cytoplasm	IEA
GO:0005856	Component	Cytoskeleton	IEA
GO:0005856	Component	Cytoskeleton	TAS	1350227
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	TAS	1350227
GO:0007010	Process	Cytoskeleton organization	IEA
GO:0008360	Process	Regulation of cell shape	IEA
GO:0016020	Component	Membrane	IEA
GO:0020027	Process	Hemoglobin metabolic process	IEA
GO:0030863	Component	Cortical cytoskeleton	IEA
GO:0043249	Process	Erythrocyte maturation	IEA
GO:0048536	Process	Spleen development	IEA
GO:0050801	Process	Monoatomic ion homeostasis	IEA
GO:0060586	Process	Multicellular organismal-level iron ion homeostasis	IEA
GO:0071944	Component	Cell periphery	IEA
GO:0170014	Component	Ankyrin-1 complex	IDA	35835865

Other IDs

• MIM: 177070
• HGNC: 3381
• e!Ensembl: ENSG00000166947

Protein

• UniProt ID: P16452
• Protein name: Protein 4.2 (P4.2) (Erythrocyte membrane protein band 4.2) (Erythrocyte protein 4.2)
• Protein function: Component of the ankyrin-1 complex, a multiprotein complex involved in the stability and shape of the erythrocyte membrane.
• PDB: 7TVZ, 7TW0, 7TW1, 7TW3, 7TW5, 7TW6, 7UZS, 7V0K, 7V0Q, 8CS9, 8CSL, 8CSW, 8CTE
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00868	Transglut_N	4 → 124	Transglutaminase family	Domain
  PF01841	Transglut_core	224 → 351	Transglutaminase-like superfamily	Family
  PF00927	Transglut_C	475 → 580	Transglutaminase family, C-terminal ig like domain	Domain
  PF00927	Transglut_C	588 → 686	Transglutaminase family, C-terminal ig like domain	Domain

• Sequence:

  MGQALGIKSCDFQAARNNEEHHTKALSSRRLFVRRGQPFTIILYFRAPVRAFLPALKKVA
  LTAQTGEQPSKINRTQATFPISSLGDRKWWSAVVEERDAQSWTISVTTPADAVIGHYSLL
  LQVSGRKQLLLGQFTLLFNPWNREDAVFLKNEAQRMEYLLNQNGLIYLGTADCIQAESWD
  FGQFEGDVIDLSLRLLSKDKQVEKWSQPVHVARVLGALLHFLKEQRVLPTPQTQATQEGA
  LLNKRRGSVPILRQWLTGRGRPVYDGQAWVLAAVACTVLRCLGIPARVVTTFASAQGTGG
  RLLIDEYYNEEGLQNGEGQRGRIWIFQTSTECWMTRPALPQGYDGWQILHPSAPNGGGVL
  GSCDLVPVRAVKEGTLGLTPAVSDLFAAINASCVVWKCCEDGTLELTDSNTKYVGNNIST
  KGVGSDRCEDITQNYKYPEGSLQEKEVLERVEKEKMEREKDNGIRPPSLETASPLYLLLK
  APSSLPLRGDAQISVTLVNHSEQEKAVQLAIGVQAVHYNGVLAAKLWRKKLHLTLSANLE
  KIITIGLFFSNFERNPPENTFLRLTAMATHSESNLSCFAQEDIAICRPHLAIKMPEKAEQ
  YQPLTASVSLQNSLDAPMEDCVISILGRGLIHRERSYRFRSVWPENTMCAKFQFTPTHVG
  LQRLTVEVDCNMFQNLTNYKSVTVVAPELSA

• Sequence length: 691

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Hereditary spherocytosis type 5	Likely pathogenic; Pathogenic	rs777764528, rs143682977, rs266257354, rs121917734, rs266257355, rs115998465, rs2142263398, rs772330879, rs2142314789	RCV001781040 RCV000119050 RCV000033190 RCV000014140 RCV000014141 RCV000014142 RCV003639378 RCV001534608 RCV001534609	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EPB42-related disorder	Conflicting classifications of pathogenicity; Likely benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Spherocytosis, Recessive	Uncertain significance; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPHEROCYTOSIS, TYPE 5	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Alpha trait thalassemia	alpha Thalassemia	BEFREE	19508687		★☆☆☆☆ Found in Text Mining only
Anemia	Anemia	Pubtator	1689063	Associate	★☆☆☆☆ Found in Text Mining only
Anemia Hemolytic	Hemolytic anemia	Pubtator	1729896, 19508687	Associate	★☆☆☆☆ Found in Text Mining only
Anemia, Hemolytic	Anemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Anemia, hereditary spherocytic hemolytic	Anemia	GENOMICS_ENGLAND_DG	1558976, 7772513		★☆☆☆☆ Found in Text Mining only
Anemia, hereditary spherocytic hemolytic	Anemia	ORPHANET_DG	23664421		★☆☆☆☆ Found in Text Mining only
Carcinoma Squamous Cell	Squamous cell carcinoma	Pubtator	25402211	Inhibit	★☆☆☆☆ Found in Text Mining only
Cholelithiasis	Cholelithiasis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Coronary Restenosis	Coronary restenosis	Pubtator	35144391	Associate	★☆☆☆☆ Found in Text Mining only
Elliptocytosis 1	Hereditary elliptocytosis	Pubtator	19508687	Associate	★☆☆☆☆ Found in Text Mining only
Elliptocytosis, Hereditary	Elliptocytosis	GENOMICS_ENGLAND_DG	1558976, 7772513		★☆☆☆☆ Found in Text Mining only
Fabry Disease	Fabry disease	Pubtator	19508687	Associate	★☆☆☆☆ Found in Text Mining only
Fibrinogen Deficiency	Fibrinogen Deficiency	HPO_DG			★☆☆☆☆ Found in Text Mining only
Gout	Gout	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hereditary spherocytosis	Hereditary Spherocytosis	LHGDN	12393467		★☆☆☆☆ Found in Text Mining only
Hereditary spherocytosis	Hereditary Spherocytosis	BEFREE	12432217, 29402830		★☆☆☆☆ Found in Text Mining only
Hereditary spherocytosis	Hereditary Spherocytosis	ORPHANET_DG	23664421		★☆☆☆☆ Found in Text Mining only
Hereditary spherocytosis	Hereditary Spherocytosis	Orphanet			★☆☆☆☆ Found in Text Mining only
Hyperbilirubinemia	Hyperbilirubinemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypofibrinogenemia	Hypofibrinogenemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Leukemia Myeloid Acute	Myeloid leukemia	Pubtator	28793301, 35003895	Associate	★☆☆☆☆ Found in Text Mining only
Lupus Erythematosus Systemic	Systemic lupus erythematosus	Pubtator	39596553	Associate	★☆☆☆☆ Found in Text Mining only
Ovarian Neoplasms	Ovarian neoplasm	Pubtator	26824454	Associate	★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	17531530	Associate	★☆☆☆☆ Found in Text Mining only
Restrictive cardiomyopathy	Restrictive cardiomyopathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Spherocytosis Hereditary	Spherocytosis	Pubtator	12176912, 20179084, 31122244, 37385619, 38069343	Associate	★☆☆☆☆ Found in Text Mining only
Spherocytosis Type 4	Spherocytosis	Pubtator	12176912	Associate	★☆☆☆☆ Found in Text Mining only
Spherocytosis, Type 5	Spherocytosis	UNIPROT_DG	10406914, 1558976, 7772513, 7819064, 8547071, 8547605		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Spherocytosis, Type 5	Spherocytosis	GENOMICS_ENGLAND_DG	1558976, 7772513		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Spherocytosis, Type 5	Spherocytosis	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Spherocytosis, Type 5	Spherocytosis	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Squamous Cell Carcinoma of Head and Neck	Squamous cell carcinoma	Pubtator	19089912	Associate	★☆☆☆☆ Found in Text Mining only
Thrombophilia	Thrombophilia	HPO_DG			★☆☆☆☆ Found in Text Mining only