EIF2B4 (eukaryotic translation initiation factor 2B subunit delta)

Gene

• Entrez ID: 8890
• Gene name: Eukaryotic translation initiation factor 2B subunit delta
• Gene symbol: EIF2B4
• Synonyms (NCBI Gene): EIF-2B, EIF2B, EIF2Bdelta, VWM4
• Chromosome: 2
• Chromosome location: 2p23.3
• Summary: Eukaryotic initiation factor 2B (EIF2B), which is necessary for protein synthesis, is a GTP exchange factor composed of five different subunits. The protein encoded by this gene is the fourth, or delta, subunit. Defects in this gene are a cause of leukoen

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs113994027	G>A	Pathogenic	Coding sequence variant, missense variant
rs113994028	C>A,T	Likely-pathogenic, uncertain-significance	Coding sequence variant, missense variant
rs113994030	G>A	Likely-pathogenic	Coding sequence variant, missense variant
rs113994035	G>A	Pathogenic	Coding sequence variant, missense variant
rs113994037	C>T	Pathogenic	Splice donor variant
rs113994038	A>G	Pathogenic	Coding sequence variant, missense variant
rs113994040	A>G	Pathogenic	Coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT028435	hsa-miR-30a-5p	Proteomics	18668040
MIRT048246	hsa-miR-196a-5p	CLASH	23622248

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001541	Process	Ovarian follicle development	IMP	15507143
GO:0002183	Process	Cytoplasmic translational initiation	IBA
GO:0002183	Process	Cytoplasmic translational initiation	IDA	27023709
GO:0003743	Function	Translation initiation factor activity	IDA	16289705
GO:0003743	Function	Translation initiation factor activity	IEA
GO:0005085	Function	Guanyl-nucleotide exchange factor activity	IDA	11323413
GO:0005085	Function	Guanyl-nucleotide exchange factor activity	IDA	25858979, 27023709
GO:0005085	Function	Guanyl-nucleotide exchange factor activity	IEA
GO:0005085	Function	Guanyl-nucleotide exchange factor activity	IMP	15054402
GO:0005515	Function	Protein binding	IPI	15060152, 25416956, 25910212, 28169297, 31515488, 32296183, 32814053, 33961781
GO:0005737	Component	Cytoplasm	IDA	11323413
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	IEA
GO:0005829	Component	Cytosol	TAS
GO:0005851	Component	Eukaryotic translation initiation factor 2B complex	IBA
GO:0005851	Component	Eukaryotic translation initiation factor 2B complex	IDA	11323413, 15060152, 27023709
GO:0005851	Component	Eukaryotic translation initiation factor 2B complex	IEA
GO:0006412	Process	Translation	IEA
GO:0006413	Process	Translational initiation	IDA	16289705
GO:0006413	Process	Translational initiation	IEA
GO:0006417	Process	Regulation of translation	NAS	12556349
GO:0007417	Process	Central nervous system development	IEA
GO:0009408	Process	Response to heat	ISS
GO:0009408	Process	Response to heat	TAS
GO:0009749	Process	Response to glucose	ISS
GO:0014003	Process	Oligodendrocyte development	IMP	15217090
GO:0031369	Function	Translation initiation factor binding	ISS
GO:0042552	Process	Myelination	IMP	14566705
GO:0043434	Process	Response to peptide hormone	ISS
GO:0048513	Process	Animal organ development	IEA
GO:0050852	Process	T cell receptor signaling pathway	IDA	8626696

Other IDs

• MIM: 606687
• HGNC: 3260
• e!Ensembl: ENSG00000115211

Protein

• UniProt ID: Q9UI10
• Protein name: Translation initiation factor eIF2B subunit delta (eIF2B GDP-GTP exchange factor subunit delta)
• Protein function: Acts as a component of the translation initiation factor 2B (eIF2B) complex, which catalyzes the exchange of GDP for GTP on eukaryotic initiation factor 2 (eIF2) gamma subunit (PubMed:25858979, PubMed:27023709, PubMed:31048492). Its guanine nucl
• PDB: 6CAJ, 6EZO, 6K71, 6K72, 6O81, 6O85, 6O9Z, 7D43, 7D44, 7D45, 7D46, 7F64, 7F66, 7F67, 7KMF, 7L70, 7L7G, 7RLO, 7TRJ, 7VLK, 8TQO, 8TQZ
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01008	IF-2B	218 → 509	Initiation factor 2 subunit family	Family

• Sequence:

  MAAVAVAVREDSGSGMKAELPPGPGAVGREMTKEEKLQLRKEKKQQKKKRKEEKGAEPET
  GSAVSAAQCQVGPTRELPESGIQLGTPREKVPAGRSKAELRAERRAKQEAERALKQARKG
  EQGGPPPKASPSTAGETPSGVKRLPEYPQVDDLLLRRLVKKPERQQVPTRKDYGSKVSLF
  SHLPQYSRQNSLTQFMSIPSSVIHPAMVRLGLQYSQGLVSGSNARCIALLRALQQVIQDY
  TTPPNEELSRDLVNKLKPYMSFLTQCRPLSASMHNAIKFLNKEITSVGSSKREEEAKSEL
  RAAIDRYVQEKIVLAAQAISRFAYQKISNGDVILVYGCSSLVSRILQEAWTEGRRFRVVV
  VDSRPWLEGRHTLRSLVHAGVPASYLLIPAASYVLPEVSKVLLGAHALLANGSVMSRVGT
  AQLALVARAHNVPVLVCCETYKFCERVQTDAFVSNELDDPDDLQCKRGEHVALANWQNHA
  SLRLLNLVYDVTPPELVDLVITELGMIPCSSVPVVLRVKSSDQ

• Sequence length: 523

Pathways

KEGG:

Herpes simplex virus 1 infection

Reactome:

Recycling of eIF2:GDP

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
Leukoencephalopathy with vanishing white matter 1	Likely pathogenic; Pathogenic	rs1332546889, rs113994030	RCV004785557 RCV004787777	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Leukoencephalopathy with vanishing white matter 4	Likely pathogenic; Pathogenic	rs113994033, rs113994037, rs113994027, rs113994038, rs113994040, rs113994039, rs113994036, rs1438809925, rs113994030	RCV003221393 RCV003221395 RCV003221396 RCV003221397 RCV003221398 RCV003448660 RCV003448661 RCV003448662 RCV003492070	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Vanishing white matter disease	Likely pathogenic; Pathogenic	rs1682246203, rs113994033, rs113994040, rs2465519163, rs113994030, rs1682104932, rs1682025430, rs1681946262	RCV002266482 RCV005417412 RCV004585985 RCV003331687 RCV001782965 RCV001198840 RCV001256671 RCV001281377	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Cervical cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHILDHOOD ATAXIA WITH CENTRAL NERVOUS SYSTEM HYPOMYELINIZATION	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EIF2B4-related disorder	Benign; Likely benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GOUT	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
VANISHING WHITE MATTER LEUKODYSTROPHY WITH OVARIAN FAILURE	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Relationship Type	References	Evidence Score
Carcinoma Hepatocellular	Associate	36524514	★☆☆☆☆ Found in Text Mining only
Cognition Disorders	Associate	25875391	★☆☆☆☆ Found in Text Mining only
Dysuria	Associate	37981684	★☆☆☆☆ Found in Text Mining only
Epstein Barr Virus Infections	Associate	20958979	★☆☆☆☆ Found in Text Mining only
Fatigue Syndrome Chronic	Associate	16049284	★☆☆☆☆ Found in Text Mining only
Leukodystrophy Metachromatic	Associate	16823698, 20958979, 22952606	★☆☆☆☆ Found in Text Mining only
Leukoencephalopathies	Associate	16823698, 20958979, 35897042, 37981684	★☆☆☆☆ Found in Text Mining only
Neoplasms	Associate	32431053	★☆☆☆☆ Found in Text Mining only
Neoplasms Cystic Mucinous and Serous	Associate	37981684	★☆☆☆☆ Found in Text Mining only
Neurodegenerative Diseases	Associate	25875391	★☆☆☆☆ Found in Text Mining only
Nevus Epithelioid and Spindle Cell	Associate	32431053	★☆☆☆☆ Found in Text Mining only
Primary Ovarian Insufficiency	Associate	32962729	★☆☆☆☆ Found in Text Mining only