EIF2S2

Summary

EIF2S2 (eukaryotic translation initiation factor 2 subunit beta, HGNC:3266) is a protein-coding gene on chromosome 20q11.22, encoding Eukaryotic translation initiation factor 2 subunit 2 (P20042). Component of the eIF2 complex that functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA. It is a common-essential gene (DepMap: required in 99.3% of cancer cell lines).

Eukaryotic translation initiation factor 2 (EIF-2) functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA and binding to a 40S ribosomal subunit. EIF-2 is composed of three subunits, alpha, beta, and gamma, with the protein encoded by this gene representing the beta subunit. The beta subunit catalyzes the exchange of GDP for GTP, which recycles the EIF-2 complex for another round of initiation. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 8894 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 30 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.3% of screened cell lines (common-essential)
• MANE Select transcript: NM_003908

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3266
Approved symbol	EIF2S2
Name	eukaryotic translation initiation factor 2 subunit beta
Location	20q11.22
Locus type	gene with protein product
Status	Approved
Aliases	EIF2beta, PPP1R67
Ensembl gene	ENSG00000125977
Ensembl biotype	protein_coding
OMIM	603908
Entrez	8894

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 13 protein_coding

ENST00000374980, ENST00000874817, ENST00000874818, ENST00000874819, ENST00000874820, ENST00000874821, ENST00000874822, ENST00000917520, ENST00000917521, ENST00000917522, ENST00000917523, ENST00000917524, ENST00000941876

RefSeq mRNA: 3 — MANE Select: NM_003908 NM_001316363, NM_001316364, NM_003908

CCDS: CCDS13231

Canonical transcript exons

ENST00000374980 — 9 exons

Exon	Start	End
ENSE00000860087	34090517	34090602
ENSE00000860088	34093675	34093731
ENSE00000860089	34096657	34096805
ENSE00000860090	34097416	34097516
ENSE00000860091	34098498	34098633
ENSE00000860092	34103462	34103565
ENSE00000860093	34105368	34105545
ENSE00001109935	34088309	34089905
ENSE00001465514	34112096	34112243

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 91.7086 / max 1440.3867, expressed in 1826 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
186980	86.5345	1826
186981	5.1742	1550

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cartilage tissue	UBERON:0002418	99.16	gold quality
oral cavity	UBERON:0000167	98.31	gold quality
gluteal muscle	UBERON:0002000	98.24	gold quality
heart right ventricle	UBERON:0002080	98.21	gold quality
trabecular bone tissue	UBERON:0002483	98.16	gold quality
deltoid	UBERON:0001476	97.94	gold quality
biceps brachii	UBERON:0001507	97.91	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.91	gold quality
triceps brachii	UBERON:0001509	97.87	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.72	gold quality
tibialis anterior	UBERON:0001385	97.60	gold quality
colonic mucosa	UBERON:0000317	97.59	gold quality
parotid gland	UBERON:0001831	97.57	gold quality
corpus epididymis	UBERON:0004359	97.34	gold quality
esophagus squamous epithelium	UBERON:0006920	97.14	gold quality
tibia	UBERON:0000979	97.10	gold quality
placenta	UBERON:0001987	97.06	gold quality
upper leg skin	UBERON:0004262	97.02	gold quality
bronchial epithelial cell	CL:0002328	96.99	gold quality
skin of hip	UBERON:0001554	96.93	gold quality
vastus lateralis	UBERON:0001379	96.84	gold quality
diaphragm	UBERON:0001103	96.83	gold quality
quadriceps femoris	UBERON:0001377	96.83	gold quality
cauda epididymis	UBERON:0004360	96.82	gold quality
caput epididymis	UBERON:0004358	96.59	gold quality
epithelium of esophagus	UBERON:0001976	96.52	gold quality
gingiva	UBERON:0001828	96.49	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.41	gold quality
skeletal muscle tissue	UBERON:0001134	96.40	gold quality
adrenal tissue	UBERON:0018303	96.38	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-HCAD-8	no	45.31
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NRF1

miRNA regulators (miRDB)

64 targeting EIF2S2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-3660	99.68	67.33	1149
HSA-MIR-4526	99.68	67.07	1136

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.3% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 6)

• These findings suggest that alpha and beta subunits of eIF2 interact with each other and the beta-subunit plays a critical role both in the regulation and function of eIF2. (PMID:18639529)
• This study provides mechanistic insight into the role of eIF5-carboxyl terminal domain’s dynamic interplay with eIF1 and eIF2beta (PMID:22813744)
• Mass spectrometry of CXCR4 immunoprecipitates revealed a specific interaction with the pentameric eukaryotic translation initiation factor 2B. (PMID:26609049)
• Data suggest that eukaryotic translation initiation factor 2 subunit beta (eIF2beta) is a therapeutic target for lung cancer. (PMID:29624814)
• RBP EIF2S2 Promotes Tumorigenesis and Progression by Regulating MYC-Mediated Inhibition via FHIT-Related Enhancers. (PMID:32059763)
• Recruitment of trimeric eIF2 by phosphatase non-catalytic subunit PPP1R15B. (PMID:38159565)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	eif2s2	ENSDARG00000053047
mus_musculus	Eif2s2	ENSMUSG00000074656
rattus_norvegicus	Eif2s2	ENSRNOG00000017447
drosophila_melanogaster	eIF2beta	FBGN0004926

Protein

Protein identifiers

Eukaryotic translation initiation factor 2 subunit 2 — P20042 (reviewed: P20042)

Alternative names: Eukaryotic translation initiation factor 2 subunit beta

All UniProt accessions (2): P20042, Q6IBR8

UniProt curated annotations — full annotation on UniProt →

Function. Component 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 eIF2B.

Subunit / interactions. Eukaryotic translation initiation factor 2 eIF2 is a heterotrimeric complex composed of an alpha (EIF2S1), a beta (EIF2S2) and a gamma (EIF2S3) chain. eIF2 is member of the 43S pre-initiation complex (43S PIC). eIF2 forms a complex with at least CELF1/CUGBP1, CALR, CALR3, EIF2S1, EIF2S2, HSP90B1 and HSPA5. EIF2S2 interacts with BZW2/5MP1. EIF2S2 interacts with EIF5. Interacts with CDC123. Interacts with methionyl-initiator methionine tRNA. (Microbial infection) Interacts with Aichi virus (AiV) leader protein.

Subcellular location. Cytoplasm. Cytosol.

Similarity. Belongs to the eIF-2-beta/eIF-5 family.

RefSeq proteins (3): NP_001303292, NP_001303293, NP_003899* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002735	Transl_init_fac_IF2/IF5_dom	Domain
IPR016189	Transl_init_fac_IF2/IF5_N	Homologous_superfamily
IPR016190	Transl_init_fac_IF2/IF5_Zn-bd	Homologous_superfamily
IPR045196	IF2/IF5	Family

Pfam: PF01873

Enzyme classification (BRENDA):

• EC 3.6.5.3 — protein-synthesizing GTPase (BRENDA: 45 organisms, 101 substrates, 61 inhibitors, 66 Km, 48 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
GTP	0.0003–0.27	53
ATP	0.12–0.2	2

UniProt features (25 total): modified residue 12, compositionally biased region 5, region of interest 2, initiator methionine 1, chain 1, zinc finger region 1, cross-link 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
8PPL	ELECTRON MICROSCOPY	2.65
9HVE	ELECTRON MICROSCOPY	2.7
6ZP4	ELECTRON MICROSCOPY	2.9
8PJ1	ELECTRON MICROSCOPY	3.4
7A09	ELECTRON MICROSCOPY	3.5
8OZ0	ELECTRON MICROSCOPY	3.5
6ZMW	ELECTRON MICROSCOPY	3.7
6YBV	ELECTRON MICROSCOPY	3.8
9HVF	ELECTRON MICROSCOPY	3.8
6K71	ELECTRON MICROSCOPY	4.3
7D43	ELECTRON MICROSCOPY	4.3
6K72	ELECTRON MICROSCOPY	4.6
7QP6	ELECTRON MICROSCOPY	4.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P20042-F1	64.98	0.27

Functional residue map

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

Post-translational modifications (13): 2, 2, 13, 31, 36, 67, 105, 111, 158, 218, 265, 293, 102

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-156827	L13a-mediated translational silencing of Ceruloplasmin expression
R-HSA-381042	PERK regulates gene expression
R-HSA-382556	ABC-family protein mediated transport
R-HSA-72649	Translation initiation complex formation
R-HSA-72695	Formation of the ternary complex, and subsequently, the 43S complex
R-HSA-72702	Ribosomal scanning and start codon recognition
R-HSA-72706	GTP hydrolysis and joining of the 60S ribosomal subunit
R-HSA-72731	Recycling of eIF2:GDP
R-HSA-9633012	Response of EIF2AK4 (GCN2) to amino acid deficiency
R-HSA-9648895	Response of EIF2AK1 (HRI) to heme deficiency
R-HSA-9833482	PKR-mediated signaling
R-HSA-9840373	Cellular response to mitochondrial stress

MSigDB gene sets: 254 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, TGCGCANK_UNKNOWN, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, BIOCARTA_RNA_PATHWAY, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GCAAGGA_MIR502, SHAFFER_IRF4_TARGETS_IN_ACTIVATED_B_LYMPHOCYTE, TATTATA_MIR374, GOBP_TRANSLATIONAL_INITIATION, MORF_HDAC2

GO Biological Process (7): in utero embryonic development (GO:0001701), formation of translation preinitiation complex (GO:0001731), male germ cell proliferation (GO:0002176), cytoplasmic translational initiation (GO:0002183), translational initiation (GO:0006413), male gonad development (GO:0008584), translation (GO:0006412)

GO Molecular Function (8): RNA binding (GO:0003723), mRNA binding (GO:0003729), translation initiation factor activity (GO:0003743), translation factor activity, RNA binding (GO:0008135), zinc ion binding (GO:0008270), translation initiation factor binding (GO:0031369), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (4): cytoplasm (GO:0005737), cytosol (GO:0005829), eukaryotic translation initiation factor 2 complex (GO:0005850), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Cap-dependent Translation Initiation	4
Cellular responses to stress	2
Eukaryotic Translation Initiation	1
Unfolded Protein Response (UPR)	1
Transport of small molecules	1
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	1
Cellular response to starvation	1
Antimicrobial mechanism of IFN-stimulated genes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
translational initiation	3
translation	2
RNA binding	2
translation factor activity	2
cellular anatomical structure	2
cytoplasm	2
chordate embryonic development	1
cytoplasmic translational initiation	1
protein-RNA complex assembly	1
germ cell proliferation	1
cytoplasmic translation	1
formation of translation initiation ternary complex	1
metabolic process	1
gonad development	1
development of primary male sexual characteristics	1
peptidyltransferase activity	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
nucleic acid binding	1
transition metal ion binding	1
protein binding	1
binding	1
cation binding	1
intracellular anatomical structure	1
protein-containing complex	1
cell junction	1

Protein interactions and networks

STRING

2690 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EIF2S2	EIF2S3	P41091	999
EIF2S2	EIF2S1	P05198	998
EIF2S2	EIF1	P41567	951
EIF2S2	RALY	Q9UKM9	933
EIF2S2	EIF5	P55010	876
EIF2S2	EIF3C	Q99613	799
EIF2S2	EIF4G1	Q04637	775
EIF2S2	RABIF	P47224	764
EIF2S2	EIF2B5	Q13144	759
EIF2S2	EIF4B	P23588	754
EIF2S2	NRF1	Q16656	703
EIF2S2	EIF2B3	Q9NR50	691
EIF2S2	EIF4A1	P04765	688
EIF2S2	EIF3A	Q14152	679
EIF2S2	ASIP	P42127	674

IntAct

207 interactions, top by confidence:

A	B	Type	Score
EIF2S3	EIF2S1	psi-mi:“MI:0407”(direct interaction)	0.820
EIF2S1	EIF2S2	psi-mi:“MI:0407”(direct interaction)	0.810
EIF2S2	EIF2S1	psi-mi:“MI:0407”(direct interaction)	0.810
EIF2S2	EIF2S1	psi-mi:“MI:0914”(association)	0.810
EIF2S1	EIF2S2	psi-mi:“MI:0914”(association)	0.810
EIF2S2	EIF2S3	psi-mi:“MI:0407”(direct interaction)	0.760
EIF2S2	CDC123	psi-mi:“MI:0914”(association)	0.710
CDC123	EIF2S2	psi-mi:“MI:0914”(association)	0.710
CDC123	EIF2S2	psi-mi:“MI:0915”(physical association)	0.710
DCC	NTN1	psi-mi:“MI:0914”(association)	0.700
MAP4K1	HSP90AB1	psi-mi:“MI:0914”(association)	0.670
JUN	EIF2S2	psi-mi:“MI:0915”(physical association)	0.670
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
CSNK2A1	EIF2S2	psi-mi:“MI:0217”(phosphorylation reaction)	0.590
EIF2S2	CHRNA4	psi-mi:“MI:0915”(physical association)	0.560
EIF2S2		psi-mi:“MI:0915”(physical association)	0.560
EIF2S2	MAP3K5	psi-mi:“MI:0915”(physical association)	0.560
NDUFV2	EIF2S2	psi-mi:“MI:0915”(physical association)	0.560
EIF2S2	NGF	psi-mi:“MI:0915”(physical association)	0.560
EIF2S2	PMP22	psi-mi:“MI:0915”(physical association)	0.560
RAB6A	EIF2S2	psi-mi:“MI:0915”(physical association)	0.560
EIF2S2	SORL1	psi-mi:“MI:0915”(physical association)	0.560
EIF2S2	KAT5	psi-mi:“MI:0915”(physical association)	0.560
APP	EIF2S2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (358): EIF2S2 (Affinity Capture-MS), EIF2S2 (Affinity Capture-MS), EIF2S2 (Affinity Capture-MS), EIF2S2 (Reconstituted Complex), EIF2S2 (Affinity Capture-MS), EIF2S2 (Affinity Capture-MS), EIF2S2 (Affinity Capture-MS), EIF2S2 (Affinity Capture-MS), EIF2S2 (Affinity Capture-MS), EIF2S3 (Affinity Capture-MS), PRMT7 (Affinity Capture-MS), EIF2S1 (Affinity Capture-MS), CDC123 (Affinity Capture-MS), EIF2S2 (Affinity Capture-MS), EIF2S2 (Affinity Capture-MS)

ESM2 similar proteins: A1C987, A4QSX4, A6QLI8, A6S043, A7E471, A8WWU0, O02328, O14164, O24473, P09064, P20042, P29083, P38431, P41035, P41375, P55010, P55871, P56329, P59325, Q07205, Q09689, Q0V1H5, Q10113, Q19753, Q21230, Q22918, Q29M42, Q2H731, Q2U0Q9, Q41969, Q4P0P0, Q54LA1, Q54T27, Q5AX75, Q5BH88, Q5E9D0, Q5R4L0, Q5R4T9, Q5RAT8, Q6C855

Diamond homologs: A0B5K5, A0B8A1, A1RUG4, A1RX59, A2SSW2, A3CXJ3, A3DNI8, A3MUE4, A4FZP0, A4WI40, A4YEI1, A5UKI8, A6URT3, A6UX55, A6VIT7, A7I5J0, A9A7T1, B0R583, B1YCG8, C3MK63, C3MU32, C3N120, C3N8N2, C3NMA3, C4KK87, C5A2A8, O24473, O27797, O27958, O58312, P09064, P20042, P41035, P41375, P55871, P56329, Q0W1F9, Q18E61, Q21230, Q2NHD9

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
CSNK2A1	up-regulates	EIF2S2	phosphorylation
EIF4G2	“up-regulates activity”	EIF2S2	binding
EIF2S2	“up-regulates quantity”	EGLN1	“translation regulation”
EIF2S2	“form complex”	Ternary_GTP_eIF2_tRNA_complex	binding
EIF2B5	“up-regulates activity”	EIF2S2	“guanine nucleotide exchange factor”
EIF2B1	“up-regulates activity”	EIF2S2	“guanine nucleotide exchange factor”
EIF2B2	“up-regulates activity”	EIF2S2	“guanine nucleotide exchange factor”
EIF2B3	“up-regulates activity”	EIF2S2	“guanine nucleotide exchange factor”
EIF2B4	“up-regulates activity”	EIF2S2	“guanine nucleotide exchange factor”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 185 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Formation of the ternary complex, and subsequently, the 43S complex	9	14.1×	3e-06
Ribosomal scanning and start codon recognition	10	13.8×	9e-07
Translation initiation complex formation	9	12.4×	6e-06
GTP hydrolysis and joining of the 60S ribosomal subunit	13	9.4×	9e-07
L13a-mediated translational silencing of Ceruloplasmin expression	12	8.8×	3e-06
Formation of a pool of free 40S subunits	10	8.1×	5e-05
SRP-dependent cotranslational protein targeting to membrane	11	8.0×	2e-05
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	9	7.7×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
formation of cytoplasmic translation initiation complex	5	33.6×	9e-05
translational initiation	8	17.2×	1e-05
regulation of translational initiation	5	14.0×	3e-03
peptidyl-tyrosine phosphorylation	5	12.6×	5e-03
cytoplasmic translation	11	12.2×	2e-06
cell surface receptor protein tyrosine kinase signaling pathway	10	10.4×	2e-05
negative regulation of translation	7	8.2×	3e-03
protein autophosphorylation	8	7.0×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1454 predictions. Top by Δscore:

Variant	Effect	Δscore
20:34089901:TTCCT:T	acceptor_gain	1.0000
20:34090515:A:AC	donor_gain	1.0000
20:34090516:C:CG	donor_gain	1.0000
20:34090600:CCA:C	acceptor_gain	1.0000
20:34090601:CA:C	acceptor_gain	1.0000
20:34090601:CAC:C	acceptor_gain	1.0000
20:34090603:C:CC	acceptor_gain	1.0000
20:34090605:A:C	acceptor_gain	1.0000
20:34091828:G:C	donor_gain	1.0000
20:34093669:TCTTA:T	donor_loss	1.0000
20:34093670:CTTA:C	donor_loss	1.0000
20:34093671:TTA:T	donor_loss	1.0000
20:34093672:TACCT:T	donor_loss	1.0000
20:34093674:C:CA	donor_loss	1.0000
20:34093729:AATC:A	acceptor_loss	1.0000
20:34093731:TC:T	acceptor_loss	1.0000
20:34093732:C:A	acceptor_loss	1.0000
20:34093732:C:CC	acceptor_gain	1.0000
20:34093733:T:C	acceptor_loss	1.0000
20:34096655:A:AC	donor_gain	1.0000
20:34096656:C:CC	donor_gain	1.0000
20:34096656:CAG:C	donor_gain	1.0000
20:34096705:A:AC	donor_gain	1.0000
20:34096706:C:CC	donor_gain	1.0000
20:34096801:AGCAG:A	acceptor_gain	1.0000
20:34096802:GCAG:G	acceptor_gain	1.0000
20:34096803:CAG:C	acceptor_gain	1.0000
20:34096803:CAGC:C	acceptor_gain	1.0000
20:34096804:AG:A	acceptor_gain	1.0000
20:34096805:GC:G	acceptor_loss	1.0000

AlphaMissense

2247 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:34089747:G:A	R329C	1.000
20:34089747:G:T	R329S	1.000
20:34089756:C:G	A326P	1.000
20:34089758:C:G	R325P	1.000
20:34089770:A:T	V321D	1.000
20:34089773:G:T	A320D	1.000
20:34089774:C:G	A320P	1.000
20:34089774:C:T	A320T	1.000
20:34089778:G:C	F318L	1.000
20:34089778:G:T	F318L	1.000
20:34089779:A:C	F318C	1.000
20:34089779:A:G	F318S	1.000
20:34089780:A:C	F318V	1.000
20:34089780:A:G	F318L	1.000
20:34089780:A:T	F318I	1.000
20:34089782:C:A	G317V	1.000
20:34089782:C:T	G317D	1.000
20:34089783:C:A	G317C	1.000
20:34089783:C:G	G317R	1.000
20:34089787:T:A	K315N	1.000
20:34089787:T:G	K315N	1.000
20:34089789:T:C	K315E	1.000
20:34089791:A:C	I314S	1.000
20:34089791:A:G	I314T	1.000
20:34089791:A:T	I314N	1.000
20:34089792:T:A	I314F	1.000
20:34089793:A:C	S313R	1.000
20:34089793:A:T	S313R	1.000
20:34089795:T:G	S313R	1.000
20:34089797:G:T	A312D	1.000

dbSNP variants (sampled 300 via entrez): RS1000013689 (20:34094459 T>C,G), RS1000159291 (20:34101903 G>T), RS1000184739 (20:34106693 G>A), RS1000394839 (20:34109911 T>A,C,G), RS1000741050 (20:34106951 G>A,T), RS1000867257 (20:34101582 G>A,C), RS1000958333 (20:34107710 G>A,T), RS1001298067 (20:34098806 G>A), RS1001405232 (20:34109939 CA>C,CAA), RS1001501457 (20:34091081 G>A,T), RS1001785269 (20:34090750 A>T), RS1002064115 (20:34111661 T>G), RS1002175603 (20:34103261 C>A), RS1002303720 (20:34096944 C>T), RS1002378336 (20:34088881 T>C)

Disease associations

OMIM: gene MIM:603908 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001683_3	Breast cancer	1.000000e-08
GCST004219_6	Skin pigmentation	2.000000e-07
GCST006867_85	Type 2 diabetes	2.000000e-08
GCST008745_27	Estimated glomerular filtration rate in non-diabetics	3.000000e-10
GCST010002_65	Refractive error	5.000000e-19

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066945 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.10	Kd	7970	nM	CHEMBL5653589
5.10	ED50	7970	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148302: Binding affinity to human EIF2S2 incubated for 45 mins by Kinobead based pull down assay	kd	7.9703	uM

CTD chemical–gene interactions

68 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression	4
sodium arsenite	increases reaction, decreases expression, increases activity, increases expression, affects binding	3
Cadmium Chloride	decreases expression, increases abundance, increases expression	3
Calcitriol	decreases expression	2
Carbamazepine	affects expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tunicamycin	increases expression	2
Thapsigargin	affects expression, increases expression	2
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
TAK-243	decreases sumoylation	1
dicrotophos	decreases expression	1
chloroacetaldehyde	affects expression	1
deoxynivalenol	affects expression	1
pyrogallol 1,3-dimethyl ether	decreases expression, affects cotreatment, affects localization	1
trichostatin A	affects expression	1
arsenite	increases reaction, affects binding	1
tetrabromobisphenol A	decreases expression	1
ochratoxin A	increases expression	1
coumarin	increases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-nonanoic acid	increases expression	1
deguelin	increases expression	1
2-palmitoylglycerol	increases expression	1
fenpyroximate	increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol B	increases expression	1
thifluzamide	increases expression	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651344	Binding	Binding affinity to human EIF2S2 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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