EIF3H

Summary

EIF3H (eukaryotic translation initiation factor 3 subunit H, HGNC:3273) is a protein-coding gene on chromosome 8q23.3-q24.11, encoding Eukaryotic translation initiation factor 3 subunit H (O15372). Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis. It is a common-essential gene (DepMap: required in 90.4% of cancer cell lines).

Enables metal-dependent deubiquitinase activity. Contributes to translation initiation factor activity. Involved in negative regulation of proteasomal ubiquitin-dependent protein catabolic process and translational initiation. Located in extracellular exosome and membrane. Part of eukaryotic translation initiation factor 3 complex. Implicated in breast cancer; prostate cancer; and prostate carcinoma. Biomarker of prostate cancer.

Source: NCBI Gene 8667 — RefSeq curated summary.

At a glance

• GWAS associations: 27
• Clinical variants (ClinVar): 73 total — 1 pathogenic
• Phenotypes (HPO): 1
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 90.4% of screened cell lines (common-essential)
• MANE Select transcript: NM_003756

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3273
Approved symbol	EIF3H
Name	eukaryotic translation initiation factor 3 subunit H
Location	8q23.3-q24.11
Locus type	gene with protein product
Status	Approved
Aliases	eIF3-gamma, eIF3-p40
Ensembl gene	ENSG00000147677
Ensembl biotype	protein_coding
OMIM	603912
Entrez	8667

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 11 protein_coding, 3 retained_intron, 2 nonsense_mediated_decay

ENST00000276682, ENST00000517974, ENST00000518034, ENST00000518949, ENST00000518995, ENST00000519046, ENST00000520289, ENST00000520813, ENST00000521861, ENST00000522453, ENST00000522800, ENST00000891872, ENST00000891873, ENST00000923016, ENST00000966244, ENST00000966245

RefSeq mRNA: 1 — MANE Select: NM_003756 NM_003756

CCDS: CCDS6319

Canonical transcript exons

ENST00000521861 — 8 exons

Exon	Start	End
ENSE00001087176	116646471	116646603
ENSE00001087177	116657215	116657314
ENSE00001123293	116642130	116645103
ENSE00003515373	116655856	116656005
ENSE00003590436	116658813	116658980
ENSE00003659548	116726016	116726172
ENSE00003686469	116755666	116755823
ENSE00003785543	116648806	116648926

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 99.50.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 241.0363 / max 4838.1266, expressed in 1828 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
94522	238.3771	1828
94515	2.5858	1230
94516	0.0575	20
94523	0.0160	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	99.50	gold quality
ganglionic eminence	UBERON:0004023	99.49	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	99.40	gold quality
left ovary	UBERON:0002119	99.37	gold quality
embryo	UBERON:0000922	99.33	gold quality
ovary	UBERON:0000992	99.33	gold quality
parotid gland	UBERON:0001831	99.31	gold quality
monocyte	CL:0000576	99.29	gold quality
leukocyte	CL:0000738	99.27	gold quality
mononuclear cell	CL:0000842	99.27	gold quality
right ovary	UBERON:0002118	99.22	gold quality
body of uterus	UBERON:0009853	99.19	gold quality
endocervix	UBERON:0000458	99.17	gold quality
lymph node	UBERON:0000029	99.15	gold quality
ectocervix	UBERON:0012249	99.15	gold quality
granulocyte	CL:0000094	99.14	gold quality
body of pancreas	UBERON:0001150	99.10	gold quality
upper leg skin	UBERON:0004262	99.09	gold quality
parietal pleura	UBERON:0002400	99.08	gold quality
ventricular zone	UBERON:0003053	99.08	gold quality
tendon of biceps brachii	UBERON:0008188	99.07	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.06	gold quality
mucosa of stomach	UBERON:0001199	99.02	gold quality
cervix squamous epithelium	UBERON:0006922	99.02	gold quality
uterine cervix	UBERON:0000002	98.99	gold quality
tibia	UBERON:0000979	98.99	gold quality
skin of hip	UBERON:0001554	98.99	gold quality
tibial artery	UBERON:0007610	98.99	gold quality
saliva-secreting gland	UBERON:0001044	98.98	gold quality
rectum	UBERON:0001052	98.98	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	88.72
E-CURD-122	yes	5.04
E-MTAB-7606	no	1238.50
E-MTAB-8207	no	560.26
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

16 targeting EIF3H, 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-627-3P	99.90	71.42	3316
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-425-5P	99.59	67.67	900
HSA-MIR-520E-5P	99.27	68.90	1513
HSA-MIR-3117-5P	99.04	67.93	618
HSA-MIR-3164	99.02	68.39	1071
HSA-MIR-6820-3P	99.02	68.50	1035
HSA-MIR-6737-3P	98.95	68.56	1577
HSA-MIR-7157-3P	98.95	68.70	1582
HSA-MIR-5008-3P	98.73	67.50	1433
HSA-MIR-4274	98.59	66.10	630
HSA-MIR-4662A-5P	98.48	67.18	1007

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 90.4% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 20)

• Gain of EIF3S3 was associated with poor cancer-specific survival in incidentally found prostate carcinomas. (PMID:11733359)
• PTK2 and EIF3S3, which, respectively, encode focal adhesion kinase and the p40 subunit of the eukaryotic initiation factor 3, were probable targets within the amplification at 8q23-q24 and may be involved in progression of HCC. (PMID:14578863)
• overexpression of EIF3S3 is associated with breast and prostate cancer (PMID:14997205)
• results suggest that eukaryotic translation initiation factor 3, subunit 3 (EIF3S3) regulates cell growth and viability, and that overexpression of the gene may provide growth advantage to the cancer cells (PMID:16652384)
• high eIF3h levels directly stimulate protein synthesis, resulting in the establishment and maintenance of the malignant state in cells. (PMID:18544531)
• MYC and EIF3H are frequently coamplified in NSCLC and that a high copy number correlates with increased epidermal growth factor receptor tyrosine kinase inhibitors sensitivity. (PMID:19204574)
• Increased expression of EIF3H gene increases colorectal cancer growth and invasiveness thereby providing a biological mechanism for the 8q23.3 association. (PMID:20862326)
• -RAD21 and EIF3H, both on chromosome 8q23, CHRAC1 on chromosome 8q24.3 and TANC2 on chromosome 17q23-were confirmed to be driver genes regulating the proliferation/survival of clonogenic breast cancer cells (PMID:24148822)
• eukaryotic translation initiation factor 3H has roles in proliferation, invasion and tumorigenicity in human hepatocellular carcinoma (PMID:27340783)
• EIF3H plays key roles in the apoptosis in colorectal cancer cells, which suggests EIF3H as a potential diagnostic biomarker in colorectal cancer (PMID:30022709)
• EIF3H knockdown inhibited cell proliferation and colony formation in gastric cancer lines and led to cell cycle arrest at the G0/G1 phase, while inducing apoptosis via up- and downregulation of pro- and anti-apoptotic factors, respectively. These results indicate that EIF3H can serve as a novel therapeutic target for the clinical treatment of gastric cancer. (PMID:30060823)
• METTL3-eIF3h interaction is required for enhanced translation, formation of densely packed polyribosomes and oncogenic transformation; findings uncover a mechanism of translation control that is based on mRNA looping and identify METTL3-eIF3h as a potential therapeutic target for patients with cancer (PMID:30232453)
• EIF3H Orchestrates Hippo Pathway-Mediated Oncogenesis via Catalytic Control of YAP Stability. (PMID:32269044)
• EIF3H promotes aggressiveness of esophageal squamous cell carcinoma by modulating Snail stability. (PMID:32867821)
• EIF3H knockdown inhibits malignant melanoma through regulating cell proliferation, apoptosis and cell cycle. (PMID:33508274)
• The effect of miR-496 on eIF3h in lung invasive adenocarcinoma. (PMID:34038061)
• EIF3H stabilizes CCND1 to promotes intrahepatic cholangiocarcinoma progression via Wnt/beta-catenin signaling. (PMID:36350008)
• Repeat polymorphisms underlie top genetic risk loci for glaucoma and colorectal cancer. (PMID:37527660)
• The deubiquitinase EIF3H promotes hepatocellular carcinoma progression by stabilizing OGT and inhibiting ferroptosis. (PMID:37559097)
• The EIF3H-HAX1 axis increases RAF-MEK-ERK signaling activity to promote colorectal cancer progression. (PMID:38514606)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000116963
mus_musculus	Eif3h	ENSMUSG00000022312
rattus_norvegicus	Eif3h	ENSRNOG00000004252
drosophila_melanogaster	eIF3h	FBGN0022023
caenorhabditis_elegans	eif-3.H	WBGENE00001231

Paralogs (3): PSMD14 (ENSG00000115233), COPS5 (ENSG00000121022), BRCC3 (ENSG00000185515)

Protein

Protein identifiers

Eukaryotic translation initiation factor 3 subunit H — O15372 (reviewed: O15372)

Alternative names: Eukaryotic translation initiation factor 3 subunit 3, eIF-3-gamma, eIF3 p40 subunit

All UniProt accessions (9): O15372, B3KS98, E5RFH0, E5RFW7, E5RGU4, E5RH59, E5RHC7, E5RJT0, Q6IB98

UniProt curated annotations — full annotation on UniProt →

Function. Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis. The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation. The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression.

Subunit / interactions. Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is composed of 13 subunits: EIF3A, EIF3B, EIF3C, EIF3D, EIF3E, EIF3F, EIF3G, EIF3H, EIF3I, EIF3J, EIF3K, EIF3L and EIF3M. The eIF-3 complex appears to include 3 stable modules: module A is composed of EIF3A, EIF3B, EIF3G and EIF3I; module B is composed of EIF3F, EIF3H, and EIF3M; and module C is composed of EIF3C, EIF3D, EIF3E, EIF3K and EIF3L. EIF3C of module C binds EIF3B of module A and EIF3H of module B, thereby linking the three modules. EIF3J is a labile subunit that binds to the eIF-3 complex via EIF3B. The eIF-3 complex interacts with RPS6KB1 under conditions of nutrient depletion. Mitogenic stimulation leads to binding and activation of a complex composed of MTOR and RPTOR, leading to phosphorylation and release of RPS6KB1 and binding of EIF4B to eIF-3. Interacts with RNF139; the interaction leads to protein translation inhibitions in a ubiquitination-dependent manner. Interacts with DHX33; the interaction is independent of RNA.

Subcellular location. Cytoplasm.

Similarity. Belongs to the eIF-3 subunit H family.

RefSeq proteins (1): NP_003747* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000555	JAMM/MPN+_dom	Domain
IPR027524	eIF3h	Family
IPR037518	MPN	Domain
IPR045810	eIF3h_C	Domain
IPR050242	JAMM_MPN+_peptidase_M67A	Family

Pfam: PF01398, PF19445

UniProt features (40 total): helix 11, turn 9, strand 9, compositionally biased region 3, region of interest 2, modified residue 2, chain 1, domain 1, sequence conflict 1, cross-link 1

Structure

Experimental structures (PDB)

27 structures.

PDB	Method	Resolution (Å)
8PPL	ELECTRON MICROSCOPY	2.65
6ZP4	ELECTRON MICROSCOPY	2.9
8PJ5	ELECTRON MICROSCOPY	2.9
8PJ6	ELECTRON MICROSCOPY	2.9
6ZON	ELECTRON MICROSCOPY	3
9KZU	ELECTRON MICROSCOPY	3
8PJ4	ELECTRON MICROSCOPY	3.2
9KN5	ELECTRON MICROSCOPY	3.2
9KRP	ELECTRON MICROSCOPY	3.2
6YBD	ELECTRON MICROSCOPY	3.3
9KKF	ELECTRON MICROSCOPY	3.3
9KN6	ELECTRON MICROSCOPY	3.3
9KZX	ELECTRON MICROSCOPY	3.3
8PJ1	ELECTRON MICROSCOPY	3.4
8PJ2	ELECTRON MICROSCOPY	3.4
8RG0	ELECTRON MICROSCOPY	3.4
7A09	ELECTRON MICROSCOPY	3.5
8OZ0	ELECTRON MICROSCOPY	3.5
8XXN	ELECTRON MICROSCOPY	3.6
6ZMW	ELECTRON MICROSCOPY	3.7
7QP7	ELECTRON MICROSCOPY	3.7
8PJ3	ELECTRON MICROSCOPY	3.7
6ZVJ	ELECTRON MICROSCOPY	3.8
9BLN	ELECTRON MICROSCOPY	3.9
7QP6	ELECTRON MICROSCOPY	4.7
3J8B	ELECTRON MICROSCOPY	9.3
3J8C	ELECTRON MICROSCOPY	11.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15372-F1	73.91	0.02

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 (3): 3, 183, 303

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-156827	L13a-mediated translational silencing of Ceruloplasmin expression
R-HSA-72649	Translation initiation complex formation
R-HSA-72689	Formation of a pool of free 40S subunits
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

MSigDB gene sets: 237 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, GOBP_CYTOPLASMIC_TRANSLATION, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GOMF_METALLOPEPTIDASE_ACTIVITY, MODULE_151, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, MORF_UBE2I, MORF_HDAC1, GOBP_MACROMOLECULE_CATABOLIC_PROCESS

GO Biological Process (6): formation of cytoplasmic translation initiation complex (GO:0001732), translational initiation (GO:0006413), regulation of translational initiation (GO:0006446), negative regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032435), cytoplasmic translational initiation (GO:0002183), translation (GO:0006412)

GO Molecular Function (6): RNA binding (GO:0003723), translation initiation factor activity (GO:0003743), metallopeptidase activity (GO:0008237), metal-dependent deubiquitinase activity (GO:0140492), protein binding (GO:0005515), peptidase activity (GO:0008233)

GO Cellular Component (8): cytosol (GO:0005829), eukaryotic translation initiation factor 3 complex (GO:0005852), membrane (GO:0016020), eukaryotic 43S preinitiation complex (GO:0016282), eukaryotic 48S preinitiation complex (GO:0033290), extracellular exosome (GO:0070062), eukaryotic translation initiation factor 3 complex, eIF3m (GO:0071541), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Cap-dependent Translation Initiation	4
Eukaryotic Translation Initiation	1
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
translational initiation	4
cellular anatomical structure	3
cytoplasm	2
cytosolic small ribosomal subunit	2
cytosolic translation preinitiation complex	2
cytoplasmic translational initiation	1
protein-RNA complex assembly	1
formation of translation initiation ternary complex	1
translation	1
metabolic process	1
regulation of translation	1
regulation of proteasomal ubiquitin-dependent protein catabolic process	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
negative regulation of proteasomal protein catabolic process	1
negative regulation of ubiquitin-dependent protein catabolic process	1
cytoplasmic translation	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
translation factor activity	1
peptidase activity	1
metallopeptidase activity	1
deubiquitinase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
protein-containing complex	1
extracellular vesicle	1
eukaryotic translation initiation factor 3 complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2302 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EIF3H	METTL3	Q86U44	989
EIF3H	EIF3B	P55884	985
EIF3H	EIF3C	Q99613	984
EIF3H	EIF3E	P60228	978
EIF3H	EIF3F	O00303	976
EIF3H	EIF3D	O15371	949
EIF3H	PSMD7	P51665	901
EIF3H	EIF3J	O75822	901
EIF3H	EIF3M	Q7L2H7	871
EIF3H	EIF3I	Q13347	864
EIF3H	TRPS1	Q9UHF7	848
EIF3H	EIF3K	Q9UBQ5	823
EIF3H	EIF3L	Q9Y262	816
EIF3H	EIF6	P56537	782
EIF3H	EIF3A	Q14152	735

IntAct

250 interactions, top by confidence:

A	B	Type	Score
EIF3M	EIF3F	psi-mi:“MI:0914”(association)	0.960
EIF3B	EIF3F	psi-mi:“MI:0915”(physical association)	0.920
EIF3A	EIF3F	psi-mi:“MI:0915”(physical association)	0.910
EIF3A	EIF3F	psi-mi:“MI:0914”(association)	0.910
EIF3H	EIF3F	psi-mi:“MI:0914”(association)	0.890
EIF3F	EIF3H	psi-mi:“MI:0915”(physical association)	0.890
EIF3F	EIF3H	psi-mi:“MI:0407”(direct interaction)	0.890
EIF3F	EIF3H	psi-mi:“MI:0914”(association)	0.890
EIF3H	EIF3M	psi-mi:“MI:0407”(direct interaction)	0.870
EIF3B	EIF3H	psi-mi:“MI:0915”(physical association)	0.830
EIF3C	EIF3F	psi-mi:“MI:0915”(physical association)	0.800
ABI3	EIF3H	psi-mi:“MI:0915”(physical association)	0.760

BioGRID (539): EIF3H (Two-hybrid), ABI2 (Two-hybrid), SORBS3 (Two-hybrid), ABI3 (Two-hybrid), EIF3H (Affinity Capture-MS), EIF3H (Affinity Capture-MS), EIF3H (Affinity Capture-MS), EIF3H (Affinity Capture-MS), EIF3B (Affinity Capture-MS), EIF3K (Affinity Capture-MS), EIF3A (Affinity Capture-MS), PRRC2B (Affinity Capture-MS), EIF3CL (Affinity Capture-MS), EIF3C (Affinity Capture-MS), EIF3M (Affinity Capture-MS)

ESM2 similar proteins: A1CQB4, A1CQH7, A1D379, A1D3E1, A2QQ10, A2QQA2, A4QT78, A4R0E5, A6RQZ9, A7E7B3, A8PZS4, B0WDA9, B0XQ55, B0XQB9, B5FY35, O04202, O15372, O43060, O74440, O82264, P0CO84, P0CO85, Q0CCM5, Q0D1J4, Q0UMR2, Q0UTQ6, Q1DHB6, Q1DRC9, Q2GZK0, Q2HGJ2, Q2U2J1, Q2UPM0, Q4PI64, Q4PI88, Q4WTA6, Q4WTH0, Q4WZP2, Q56JZ5, Q5BB47, Q5BDW0

Diamond homologs: A1CQB4, A1D379, A2QQA2, A4QT78, A6RQZ9, A7E7B3, A7SA47, A8QCY3, A9V3P1, B0WDA9, B0XQB9, B5FY35, B5RI54, O15372, Q0D1J4, Q0UMR2, Q170C2, Q1DHB6, Q2GZK0, Q2U2J1, Q4PI64, Q4WTA6, Q54UD0, Q56JZ5, Q5BDW0, Q5PPY6, Q5PR67, Q5ZLE6, Q6AXJ2, Q6C1I3, Q6P381, Q6P9U8, Q7PVR3, Q7S9Y9, Q91WK2, Q9C5Z2, Q9GV27, Q9UT48, O01974, A3QVV1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
EIF3H	“form complex”	EIF3_complex	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 138 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
Ribosomal scanning and start codon recognition	21	40.4×	1e-26
Formation of the ternary complex, and subsequently, the 43S complex	18	39.2×	7e-23
Translation initiation complex formation	20	38.5×	4e-25
GTP hydrolysis and joining of the 60S ribosomal subunit	24	24.3×	4e-25
L13a-mediated translational silencing of Ceruloplasmin expression	23	23.5×	8e-24
Formation of a pool of free 40S subunits	20	22.6×	3e-20
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	7	19.2×	3e-06
Eukaryotic Translation Initiation	5	15.6×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
formation of cytoplasmic translation initiation complex	14	126.8×	8e-27
translational initiation	18	52.0×	2e-24
regulation of translational initiation	7	26.4×	1e-06
negative regulation of proteasomal ubiquitin-dependent protein catabolic process	5	16.2×	1e-03
cytoplasmic translation	10	14.9×	3e-07
positive regulation of translation	6	11.0×	1e-03
negative regulation of translation	6	9.5×	2e-03
translation	10	8.3×	4e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	50
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1703572	GRCh37/hg19 8q23.3-24.11(chr8:115662767-117718250)	Pathogenic

SpliceAI

1869 predictions. Top by Δscore:

Variant	Effect	Δscore
8:116646465:CAATA:C	donor_loss	1.0000
8:116646466:AATAC:A	donor_loss	1.0000
8:116646467:ATACC:A	donor_loss	1.0000
8:116646468:TA:T	donor_loss	1.0000
8:116646470:C:CA	donor_loss	1.0000
8:116646492:T:TA	donor_gain	1.0000
8:116646599:TGATA:T	acceptor_gain	1.0000
8:116646600:GATA:G	acceptor_gain	1.0000
8:116646600:GATAC:G	acceptor_gain	1.0000
8:116646601:ATA:A	acceptor_gain	1.0000
8:116646601:ATACT:A	acceptor_gain	1.0000
8:116646602:TA:T	acceptor_gain	1.0000
8:116646602:TAC:T	acceptor_loss	1.0000
8:116646602:TACT:T	acceptor_gain	1.0000
8:116646603:ACT:A	acceptor_gain	1.0000
8:116646604:C:CC	acceptor_gain	1.0000
8:116646609:A:AC	acceptor_gain	1.0000
8:116646609:A:C	acceptor_gain	1.0000
8:116646612:C:CT	acceptor_gain	1.0000
8:116646613:A:T	acceptor_gain	1.0000
8:116648802:CAAC:C	donor_loss	1.0000
8:116648804:AC:A	donor_loss	1.0000
8:116648805:CCT:C	donor_loss	1.0000
8:116648927:C:CC	acceptor_gain	1.0000
8:116655849:CACTT:C	donor_loss	1.0000
8:116655850:ACTTA:A	donor_loss	1.0000
8:116655851:CTTAC:C	donor_loss	1.0000
8:116655852:TTAC:T	donor_loss	1.0000
8:116655853:TA:T	donor_loss	1.0000
8:116655855:C:CT	donor_loss	1.0000

AlphaMissense

2337 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:116646569:C:G	R288P	1.000
8:116646570:G:T	R288S	1.000
8:116646590:C:G	R281P	1.000
8:116657275:G:T	A166E	1.000
8:116658821:A:G	L150P	1.000
8:116658821:A:T	L150H	1.000
8:116658824:A:T	V149D	1.000
8:116658827:A:T	V148D	1.000
8:116658830:G:A	S147F	1.000
8:116658831:A:G	S147P	1.000
8:116658848:T:G	Q141P	1.000
8:116658852:A:C	Y140D	1.000
8:116658852:A:G	Y140H	1.000
8:116658860:T:G	Q137P	1.000
8:116658864:A:G	S136P	1.000
8:116658912:A:C	Y120D	1.000
8:116658912:A:G	Y120H	1.000
8:116658913:C:A	W119C	1.000
8:116658913:C:G	W119C	1.000
8:116658915:A:G	W119R	1.000
8:116658915:A:T	W119R	1.000
8:116658917:C:A	G118V	1.000
8:116658917:C:T	G118D	1.000
8:116658918:C:A	G118C	1.000
8:116658918:C:G	G118R	1.000
8:116658918:C:T	G118S	1.000
8:116658924:G:C	H116D	1.000
8:116658926:A:G	L115P	1.000
8:116658932:T:A	D113V	1.000
8:116658932:T:C	D113G	1.000

dbSNP variants (sampled 300 via entrez): RS1000024936 (8:116712258 A>G), RS1000040446 (8:116653068 G>C), RS1000049573 (8:116659050 C>T), RS1000088817 (8:116730431 C>T), RS1000119913 (8:116730643 G>A,C), RS1000172186 (8:116686355 G>A), RS1000266659 (8:116753734 A>C), RS1000269649 (8:116718072 G>A), RS1000275754 (8:116641957 A>C), RS1000294330 (8:116765679 T>C,G), RS1000324753 (8:116730572 C>A,T), RS1000353410 (8:116758866 G>C), RS1000363060 (8:116665251 C>G), RS1000369519 (8:116724345 T>C), RS1000371868 (8:116723198 A>T)

Disease associations

OMIM: gene MIM:603912 | disease phenotypes: MIM:614701, MIM:190350, MIM:209850

GenCC curated gene-disease

Mondo (3): Cornelia de Lange syndrome 4 (MONDO:0013864), trichorhinophalangeal syndrome type I (MONDO:0008596), autism (MONDO:0005260)

Orphanet (2): Cornelia de Lange syndrome (Orphanet:199), Trichorhinophalangeal syndrome type 1 (Orphanet:77258)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000717	Autism

GWAS associations

27 associations (top):

Study	Trait	p-value
GCST000169_2	Colorectal cancer	3.000000e-18
GCST001161_4	Colorectal cancer	4.000000e-07
GCST001680_6	Corneal curvature	7.000000e-06
GCST002411_8	Colorectal cancer	2.000000e-08
GCST002545_4	Ossification of the posterior longitudinal ligament of the spine	1.000000e-10
GCST002783_72	Body mass index	6.000000e-06
GCST002919_7	Colorectal cancer	2.000000e-11
GCST003017_14	Colorectal cancer	3.000000e-12
GCST003799_29	Colorectal cancer	1.000000e-15
GCST003799_3	Colorectal cancer	1.000000e-12
GCST003799_4	Colorectal cancer	2.000000e-12
GCST004025_12	Systemic juvenile idiopathic arthritis	2.000000e-06
GCST005212_10	Asthma	2.000000e-06
GCST005591_5	Colorectal cancer	5.000000e-07
GCST006224_4	Right lateral prefrontal cortical growth	7.000000e-06
GCST007552_11	Colorectal cancer	2.000000e-10
GCST007552_8	Colorectal cancer	2.000000e-14
GCST007565_64	Morning person	4.000000e-16
GCST007856_24	Colorectal cancer or advanced adenoma	4.000000e-32
GCST007856_52	Colorectal cancer or advanced adenoma	6.000000e-10
GCST007856_55	Colorectal cancer or advanced adenoma	2.000000e-16
GCST007856_7	Colorectal cancer or advanced adenoma	4.000000e-08
GCST008161_55	Waist circumference adjusted for body mass index	5.000000e-06
GCST008839_532	Height	1.000000e-10
GCST009391_1594	Metabolite levels	7.000000e-06
GCST012226_756	Waist circumference adjusted for body mass index	1.000000e-08
GCST90020028_311	Hip circumference adjusted for BMI	3.000000e-09

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004345	corneal topography
EFO:0004340	body mass index
EFO:0008328	chronotype measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0010376	phosphatidylcholine 34:2 measurement
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
C536820	Trichorhinophalangeal Syndrome, Type I (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067045 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.75	Kd	179	nM	CHEMBL5653589
6.75	ED50	179	nM	CHEMBL5653589
5.85	Kd	1400	nM	CHEMBL3752910
5.85	ED50	1400	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 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	2148144: Binding affinity to human EIF3H incubated for 45 mins by Kinobead based pull down assay	kd	0.1790	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148144: Binding affinity to human EIF3H incubated for 45 mins by Kinobead based pull down assay	kd	1.4003	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Fluorouracil	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
2,4,6-tribromophenol	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
methylparaben	decreases expression	1
sodium arsenite	decreases expression	1
tetrabromobisphenol A	decreases expression	1
aflatoxin B2	decreases methylation	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
bisphenol B	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Sunitinib	increases expression	1
Benzo(a)pyrene	affects methylation	1
Benztropine	decreases expression	1
Caffeine	increases phosphorylation	1
Doxorubicin	increases expression	1
Ivermectin	decreases expression	1
Ribonucleotides	affects binding	1
Tobacco Smoke Pollution	affects expression	1
Tretinoin	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651186	Binding	Binding affinity to human EIF3H 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

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1QW	Abcam HeLa EIF3H KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
NCT00346736	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00352248	PHASE3	COMPLETED	Randomized Controlled Trial of Acupuncture Versus Sham Acupuncture in Autistic Spectrum Disorder
NCT00352352	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00355329	PHASE3	COMPLETED	Randomized Control Trial of Using Tongue Acupuncture in Autistic Spectrum Disorder Using PET Scan for Clinical Correlation
NCT00498173	PHASE3	COMPLETED	Effectiveness of Atomoxetine in Treating ADHD Symptoms in Children and Adolescents With Autism
NCT00541346	PHASE3	COMPLETED	A Pilot Study of Daytrana TM in Children With Autism Co-Morbid for Attention Deficit Hyperactivity Disorder (ADHD) Symptoms