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
CONGENITAL OR EARLY INFANTILE CACH SYNDROME	—	Disgenet, Orphanet Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CREE LEUKOENCEPHALOPATHY	—	Orphanet	★★☆☆☆ 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	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adenocarcinoma of lung (disorder)	Lung adenocarcinoma	CTD_human_DG	24366584		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	31119045		★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	36524514	Associate	★☆☆☆☆ Found in Text Mining only
Central nervous system demyelination	Central Nervous System Demyelination	HPO_DG			★☆☆☆☆ Found in Text Mining only
Childhood Ataxia with Central Nervous System Hypomyelinization	Leukoencephalopathy with vanishing white matter	BEFREE	11704758, 11835386, 12707859, 14993275, 15054402, 15217090, 15723074, 16041584, 16047349, 16246152, 16246171, 16823698, 16998732, 19023445, 19158808, 20016818, 25843247, 26162493, 26671108, 28093708, 28306143, 30279648, 30720246, 31134486, 31385086, 31587290		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Childhood Ataxia with Central Nervous System Hypomyelinization	Leukoencephalopathy with vanishing white matter	UNIPROT_DG	11835386, 12707859, 15776425		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Childhood Ataxia with Central Nervous System Hypomyelinization	Leukoencephalopathy with vanishing white matter	GENOMICS_ENGLAND_DG	12707859, 24357685, 25089094, 26043506, 30073106		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Childhood Ataxia with Central Nervous System Hypomyelinization	Leukoencephalopathy with vanishing white matter	ORPHANET_DG	15136673		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cognition Disorders	Cognition disorder	Pubtator	25875391	Associate	★☆☆☆☆ Found in Text Mining only
Cree leukoencephalopathy	Cree Leukoencephalopathy	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Delusions	Delusions	HPO_DG			★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Development Disorder	BEFREE	22952606		★☆☆☆☆ Found in Text Mining only
Developmental regression	Developmental regression	HPO_DG			★☆☆☆☆ Found in Text Mining only
Diffuse Scleroderma	Scleroderma	BEFREE	29294089		★☆☆☆☆ Found in Text Mining only
Down Syndrome	Down Syndrome	BEFREE	31727829		★☆☆☆☆ Found in Text Mining only
Dysarthria	Dysarthria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Encephalopathies	Epileptic encephalopathy	BEFREE	14566705, 15021247, 15054402		★☆☆☆☆ Found in Text Mining only
Fatigue Syndrome Chronic	Fatigue syndrome	Pubtator	16049284	Associate	★☆☆☆☆ Found in Text Mining only
Impaired cognition	Impaired Cognition	BEFREE	20016818		★☆☆☆☆ Found in Text Mining only
Late infantile CACH syndrome	CACH Syndrome	Orphanet			★☆☆☆☆ Found in Text Mining only
Leukodystrophy	Leukodystrophy	BEFREE	15021247, 15054402, 15136673, 15723074, 16041584, 16378743, 18005052, 18263758, 18519871, 18678442, 20016818, 20958979, 22678813, 22737209, 22952606, 26974157, 29632131, 29740943, 30115954, 30279648, 31134486		★☆☆☆☆ Found in Text Mining only
Leukodystrophy Metachromatic	Metachromatic leukodystrophy	Pubtator	16823698, 20958979, 22952606	Associate	★☆☆☆☆ Found in Text Mining only
Leukoencephalopathy	Leukoencephalopathy	BEFREE	12499492, 14566705, 21560189, 24938145, 26625702, 30720246		★☆☆☆☆ Found in Text Mining only
Leukoencephalopathy	Leukoencephalopathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Lung Diseases, Interstitial	Lung Diseases	BEFREE	29294089		★☆☆☆☆ Found in Text Mining only
Macrocephaly	Macrocephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	31119045		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	29036434		★☆☆☆☆ Found in Text Mining only
melanoma	Melanoma	BEFREE	28096186		★☆☆☆☆ Found in Text Mining only
Mood swings	Mood swings	HPO_DG			★☆☆☆☆ Found in Text Mining only
Multiple Sclerosis	Multiple Sclerosis	BEFREE	18632786, 26671108, 28093708		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	30538549		★☆☆☆☆ Found in Text Mining only
nervous system disorder	Nervous System Disorder	BEFREE	22238342, 26614666		★☆☆☆☆ Found in Text Mining only
Neurodegenerative Diseases	Neurodegenerative disorder	Pubtator	25875391	Associate	★☆☆☆☆ Found in Text Mining only
Neurodegenerative Disorders	Neurodegenerative Disorders	BEFREE	14729329, 15060152, 16246171, 22678813, 23335982, 28306143, 28597716, 29036434, 29489452		★☆☆☆☆ Found in Text Mining only
Optic Atrophy	Optic Atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ovarian Failure, Premature	Ovarian Failure	BEFREE	15021247		★☆☆☆☆ Found in Text Mining only
OVARIOLEUKODYSTROPHY	Ovarioleukodystrophy	CTD_human_DG	12707859		★☆☆☆☆ Found in Text Mining only
OVARIOLEUKODYSTROPHY	Ovarioleukodystrophy	BEFREE	15054402, 18005052, 18061208, 18263758		★☆☆☆☆ Found in Text Mining only
OVARIOLEUKODYSTROPHY	Ovarioleukodystrophy	ORPHANET_DG	15136673		★☆☆☆☆ Found in Text Mining only
Ovarioleukodystrophy	Ovarioleukodystrophy	Orphanet			★☆☆☆☆ Found in Text Mining only
Parkinson Disease	Parkinson disease	BEFREE	15986317		★☆☆☆☆ Found in Text Mining only
Premature Menopause	Premature Menopause	BEFREE	15021247		★☆☆☆☆ Found in Text Mining only
Premature Menopause	Premature Menopause	HPO_DG			★☆☆☆☆ Found in Text Mining only
Primary physiologic amenorrhea	Physiologic Amenorrhea	HPO_DG			★☆☆☆☆ Found in Text Mining only
Scleroderma	Scleroderma	BEFREE	29294089		★☆☆☆☆ Found in Text Mining only
Secondary physiologic amenorrhea	Secondary Physiologic Amenorrhea	HPO_DG			★☆☆☆☆ Found in Text Mining only
Systemic Scleroderma	Scleroderma	BEFREE	29294089		★☆☆☆☆ Found in Text Mining only