EIF2S3B

Summary

EIF2S3B (eukaryotic translation initiation factor 2 subunit gamma B, HGNC:43863) is a protein-coding gene on chromosome 12p13.2, encoding Eukaryotic translation initiation factor 2 subunit 3B (Q2VIR3). Member of the eIF2 complex that functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA.

Predicted to enable translation initiation factor activity. Predicted to contribute to tRNA binding activity. Predicted to be involved in formation of translation preinitiation complex. Predicted to act upstream of or within positive regulation of male gonad development and spermatogenesis. Predicted to be part of eukaryotic translation initiation factor 2 complex.

Source: NCBI Gene 255308 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 3 total
• MANE Select transcript: NM_001357734

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:43863
Approved symbol	EIF2S3B
Name	eukaryotic translation initiation factor 2 subunit gamma B
Location	12p13.2
Locus type	gene with protein product
Status	Approved
Aliases	eIF2gA, eIF-2-gamma2
Ensembl gene	ENSG00000180574
Ensembl biotype	protein_coding
Entrez	255308

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000322446, ENST00000538173

RefSeq mRNA: 2 — MANE Select: NM_001357734 NM_001357731, NM_001357734

CCDS: CCDS86282, CCDS91654

Canonical transcript exons

ENST00000538173 — 1 exons

Exon	Start	End
ENSE00002304914	10505890	10508525

Expression profiles

Bgee: expression breadth ubiquitous, 103 present calls, max score 82.04.

Top tissues by expression

119 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.04	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	65.99	gold quality
stromal cell of endometrium	CL:0002255	59.22	gold quality
cortical plate	UBERON:0005343	57.92	gold quality
bone marrow cell	CL:0002092	57.84	silver quality
duodenum	UBERON:0002114	57.36	gold quality
ventricular zone	UBERON:0003053	56.77	gold quality
testis	UBERON:0000473	54.67	gold quality
right testis	UBERON:0004534	54.59	gold quality
skeletal muscle tissue	UBERON:0001134	53.12	gold quality
left testis	UBERON:0004533	53.11	gold quality
ganglionic eminence	UBERON:0004023	52.71	gold quality
bone marrow	UBERON:0002371	52.51	silver quality
rectum	UBERON:0001052	51.63	gold quality
muscle tissue	UBERON:0002385	50.32	gold quality
transverse colon	UBERON:0001157	48.70	gold quality
colonic epithelium	UBERON:0000397	48.44	gold quality
lower esophagus mucosa	UBERON:0035834	46.97	silver quality
urinary bladder	UBERON:0001255	46.85	gold quality
leukocyte	CL:0000738	46.19	gold quality
lymph node	UBERON:0000029	46.15	gold quality
hindlimb stylopod muscle	UBERON:0004252	46.11	silver quality
prefrontal cortex	UBERON:0000451	45.70	gold quality
colon	UBERON:0001155	44.94	gold quality
smooth muscle tissue	UBERON:0001135	44.76	gold quality
intestine	UBERON:0000160	44.73	gold quality
monocyte	CL:0000576	44.57	gold quality
vermiform appendix	UBERON:0001154	44.41	gold quality
small intestine	UBERON:0002108	44.13	gold quality
mucosa of transverse colon	UBERON:0004991	43.98	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.58

Regulation

Is transcription factor: no

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	eif2s3	ENSDARG00000008292
mus_musculus	Eif2s3x	ENSMUSG00000035150
rattus_norvegicus	Eif2s3y	ENSRNOG00000060048
drosophila_melanogaster	mEFTu2	FBGN0033184
drosophila_melanogaster	eIF2gamma	FBGN0263740
caenorhabditis_elegans	tufm-2	WBGENE00007001
caenorhabditis_elegans	eif-2gamma	WBGENE00021466

Paralogs (18): MTIF2 (ENSG00000085760), GTPBP1 (ENSG00000100226), EEF1A2 (ENSG00000101210), GSPT1 (ENSG00000103342), EFTUD2 (ENSG00000108883), HBS1L (ENSG00000112339), EIF2S3 (ENSG00000130741), EEFSEC (ENSG00000132394), EFL1 (ENSG00000140598), GUF1 (ENSG00000151806), EEF1A1 (ENSG00000156508), EIF5B (ENSG00000158417), GFM2 (ENSG00000164347), EEF2 (ENSG00000167658), GFM1 (ENSG00000168827), GTPBP2 (ENSG00000172432), TUFM (ENSG00000178952), GSPT2 (ENSG00000189369)

Protein

Protein identifiers

Eukaryotic translation initiation factor 2 subunit 3B — Q2VIR3 (reviewed: Q2VIR3)

Alternative names: Eukaryotic translation initiation factor 2 subunit gamma A

All UniProt accessions (1): Q2VIR3

UniProt curated annotations — full annotation on UniProt →

Function. Member of the eIF2 complex that functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA. This complex binds to a 40S ribosomal subunit, followed by mRNA binding to form the 43S pre-initiation complex (43S PIC). Junction of the 60S ribosomal subunit to form the 80S initiation complex is preceded by hydrolysis of the GTP bound to eIF2 and release of an eIF2-GDP binary complex. In order for eIF2 to recycle and catalyze another round of initiation, the GDP bound to eIF2 must exchange with GTP by way of a reaction catalyzed by eIF-2B.

Subunit / interactions. eIF2 is a heterotrimer composed of an alpha, a beta and a gamma chain. eIF2 is member of the 43S pre-initiation complex (43S PIC).

Tissue specificity. Specifically expressed in testis at the mRNA level.

Similarity. Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. EIF2G subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q2VIR3-1	1	yes
Q2VIR3-2	2

RefSeq proteins (2): NP_001344660, NP_001344663* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000795	T_Tr_GTP-bd_dom	Domain
IPR004161	EFTu-like_2	Domain
IPR009000	Transl_B-barrel_sf	Homologous_superfamily
IPR009001	Transl_elong_EF1A/Init_IF2_C	Homologous_superfamily
IPR015256	eIF2g_C	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR044127	eIF2g_dom_2	Domain
IPR044128	eIF2g_GTP-bd	Domain
IPR050543	eIF2G	Family

Pfam: PF00009, PF03144, PF09173

Catalyzed reactions (Rhea), 1 shown:

• GTP + H2O = GDP + phosphate + H(+) (RHEA:19669)

UniProt features (21 total): sequence conflict 7, region of interest 5, binding site 3, modified residue 2, initiator methionine 1, chain 1, splice variant 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q2VIR3-F1	85.40	0.39

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (3): 225–227; 51–56; 190–193

Post-translational modifications (2): 2, 16

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 21 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, GOBP_TRANSLATIONAL_INITIATION, GOMF_TRANSLATION_INITIATION_FACTOR_ACTIVITY, GOBP_TRANSLATION, GOBP_FORMATION_OF_TRANSLATION_PREINITIATION_COMPLEX, GOBP_CYTOPLASMIC_TRANSLATIONAL_INITIATION, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, GOMF_GTPASE_ACTIVITY, GOMF_TRNA_BINDING, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ACID_ANHYDRIDES, GOCC_EUKARYOTIC_TRANSLATION_INITIATION_FACTOR_2_COMPLEX, DESCARTES_MAIN_FETAL_ELF3_AGBL2_POSITIVE_CELLS, GOMF_GUANYL_NUCLEOTIDE_BINDING, LIU_OVARIAN_CANCER_TUMORS_AND_XENOGRAFTS_XDGS_DN

GO Biological Process (3): formation of translation preinitiation complex (GO:0001731), translation (GO:0006412), translational initiation (GO:0006413)

GO Molecular Function (6): tRNA binding (GO:0000049), translation initiation factor activity (GO:0003743), GTPase activity (GO:0003924), GTP binding (GO:0005525), nucleotide binding (GO:0000166), hydrolase activity (GO:0016787)

GO Cellular Component (1): eukaryotic translation initiation factor 2 complex (GO:0005850)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
translational initiation	2
cytoplasmic translational initiation	1
protein-RNA complex assembly	1
peptidyltransferase activity	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
formation of translation initiation ternary complex	1
translation	1
metabolic process	1
RNA binding	1
translation factor activity	1
ribonucleoside triphosphate phosphatase activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
catalytic activity	1
cytoplasm	1
protein-containing complex	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

16 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
	TK2	psi-mi:“MI:0915”(physical association)	0.400
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
DLD	NFKBIE	psi-mi:“MI:0914”(association)	0.350
DNM1L		psi-mi:“MI:0914”(association)	0.350
DLD	IRS4	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
TAGLN	LOC392647	psi-mi:“MI:0914”(association)	0.350
BMI1	MEIS3P1	psi-mi:“MI:0914”(association)	0.350
RYBP	PIPSL	psi-mi:“MI:0914”(association)	0.350
AFG2A	ESYT2	psi-mi:“MI:0914”(association)	0.350
NSS	DDX3X	psi-mi:“MI:0914”(association)	0.350
CDC5L		psi-mi:“MI:0914”(association)	0.350

ESM2 similar proteins: A0A1L8EV45, C9WPN6, F1QGW6, F6RQL9, O73723, O77676, P00516, P0C605, P20461, P23258, P23330, P31321, P32392, P35250, P41091, P53033, P61157, P61158, P62482, P62483, P81795, P83887, P83888, Q05B83, Q0VCD2, Q13126, Q13303, Q13976, Q27955, Q2KHU8, Q2KJ81, Q2VIR3, Q32KM1, Q4V7C7, Q5R797, Q5R8R1, Q5ZHS1, Q5ZMS3, Q641P0, Q641W4

Diamond homologs: A1AVJ8, A1AX82, A1UBL1, A2BT83, A3CP09, A3PV96, A4FPM7, A4FWW9, A4VTQ7, A4VZZ3, A5CW32, A5GIP0, A5GW14, A6UPK8, A6UTL4, A6VGE8, A7HWP7, A8AWA0, A9AAA4, A9BCK0, B0R6Y7, B1ICR4, B1MGH7, B1VET1, B5E653, B6YW69, B8ZL95, B9DRL9, B9LSM6, C1C881, C1CF71, C1CLI6, C1CSB0, C9WPN6, F1QGW6, J9VR81, O26361, O29663, O36041, O59410

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

3 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	1
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

139 predictions. Top by Δscore:

Variant	Effect	Δscore
12:10506870:C:CA	acceptor_gain	0.6500
12:10506729:G:T	donor_gain	0.5600
12:10506745:T:TA	donor_gain	0.5600
12:10506746:A:AA	donor_gain	0.5600
12:10506862:A:AG	acceptor_gain	0.5300
12:10506728:G:GT	donor_gain	0.5000
12:10506743:GGT:G	donor_gain	0.4900
12:10507037:A:AG	acceptor_gain	0.4700
12:10507038:G:GG	acceptor_gain	0.4700
12:10506734:GT:G	donor_gain	0.4300
12:10506870:CGG:C	acceptor_gain	0.4300
12:10506878:A:AG	acceptor_gain	0.4100
12:10507037:AGACG:A	acceptor_gain	0.4100
12:10507038:GACGG:G	acceptor_gain	0.4100
12:10506729:G:GT	donor_gain	0.4000
12:10506871:G:A	acceptor_gain	0.4000
12:10507036:TAGAC:T	acceptor_gain	0.4000
12:10506002:G:GT	donor_gain	0.3900
12:10506788:G:GG	donor_gain	0.3900
12:10506605:GTTT:G	donor_gain	0.3800
12:10506787:A:AG	donor_gain	0.3800
12:10506863:C:G	acceptor_gain	0.3600
12:10506747:G:GG	donor_gain	0.3500
12:10505976:TTACC:T	donor_gain	0.3300
12:10506277:A:G	donor_gain	0.3300
12:10506448:G:GT	donor_gain	0.3300
12:10506872:G:C	acceptor_gain	0.3300
12:10507038:GAC:G	acceptor_gain	0.3300
12:10506006:T:G	donor_gain	0.3200
12:10506554:G:GT	donor_gain	0.3200

AlphaMissense

3065 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:10506044:G:C	G48R	1.000
12:10506045:G:A	G48D	1.000
12:10506045:G:T	G48V	1.000
12:10506050:G:C	V50L	1.000
12:10506050:G:T	V50L	1.000
12:10506059:G:T	G53W	1.000
12:10506060:G:A	G53E	1.000
12:10506062:A:C	K54Q	1.000
12:10506063:A:T	K54I	1.000
12:10506066:C:T	S55F	1.000
12:10506147:G:A	G82E	1.000
12:10506300:T:A	V133D	1.000
12:10506302:G:C	D134H	1.000
12:10506303:A:C	D134A	1.000
12:10506303:A:T	D134V	1.000
12:10506305:T:C	C135R	1.000
12:10506306:G:A	C135Y	1.000
12:10506307:T:G	C135W	1.000
12:10506309:C:A	P136H	1.000
12:10506311:G:C	G137R	1.000
12:10506311:G:T	G137C	1.000
12:10506312:G:A	G137D	1.000
12:10506312:G:T	G137V	1.000
12:10506314:C:G	H138D	1.000
12:10506315:A:G	H138R	1.000
12:10506316:C:A	H138Q	1.000
12:10506316:C:G	H138Q	1.000
12:10506318:A:T	D139V	1.000
12:10506324:T:C	L141S	1.000
12:10506327:T:A	M142K	1.000

dbSNP variants (sampled 300 via entrez): RS1000030104 (12:10523302 A>G), RS1000102923 (12:10513523 T>C,G), RS1000337608 (12:10511100 C>G,T), RS1000373401 (12:10510727 C>T), RS1000550424 (12:10510411 A>G), RS1000653811 (12:10523036 G>A), RS1001320762 (12:10520162 A>C), RS1001335246 (12:10515663 G>A), RS1001372698 (12:10520639 T>C), RS1001508008 (12:10504096 A>G), RS1001704713 (12:10521707 A>C), RS1001994644 (12:10513409 T>C), RS1002011719 (12:10509455 T>G), RS1002044153 (12:10509205 T>A), RS1002225905 (12:10508668 C>A)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
di-n-butylphosphoric acid	affects expression	1
Arsenic Trioxide	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Tretinoin	affects cotreatment, decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.