EIF3I

Summary

EIF3I (eukaryotic translation initiation factor 3 subunit I, HGNC:3272) is a protein-coding gene on chromosome 1p35.2, encoding Eukaryotic translation initiation factor 3 subunit I (Q13347). 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 99.8% of cancer cell lines).

Contributes to translation initiation factor activity. Involved in translational initiation. Located in extracellular exosome. Part of eukaryotic translation initiation factor 3 complex.

Source: NCBI Gene 8668 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Moderate, GenCC)
• Clinical variants (ClinVar): 30 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_003757

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3272
Approved symbol	EIF3I
Name	eukaryotic translation initiation factor 3 subunit I
Location	1p35.2
Locus type	gene with protein product
Status	Approved
Aliases	TRIP-1, eIF3-beta, eIF3-p36
Ensembl gene	ENSG00000084623
Ensembl biotype	protein_coding
OMIM	603911
Entrez	8668

Gene structure

Transcript identifiers

Ensembl transcripts: 49 — 28 protein_coding, 11 nonsense_mediated_decay, 10 retained_intron

ENST00000355082, ENST00000373586, ENST00000471486, ENST00000474371, ENST00000483517, ENST00000489353, ENST00000676554, ENST00000676679, ENST00000676801, ENST00000676837, ENST00000676957, ENST00000676998, ENST00000677053, ENST00000677183, ENST00000677198, ENST00000677202, ENST00000677353, ENST00000677378, ENST00000677540, ENST00000677580, ENST00000677640, ENST00000677676, ENST00000677701, ENST00000677711, ENST00000677760, ENST00000677767, ENST00000677772, ENST00000677844, ENST00000678063, ENST00000678106, ENST00000678150, ENST00000678162, ENST00000678306, ENST00000678420, ENST00000678534, ENST00000678689, ENST00000678711, ENST00000678842, ENST00000678883, ENST00000678889, ENST00000678968, ENST00000679044, ENST00000679270, ENST00000679290, ENST00000918997, ENST00000918998, ENST00000956082, ENST00000956083, ENST00000956084

RefSeq mRNA: 2 — MANE Select: NM_003757 NM_001394168, NM_003757

CCDS: CCDS357, CCDS90907

Canonical transcript exons

ENST00000677711 — 11 exons

Exon	Start	End
ENSE00001306346	32230927	32231019
ENSE00001460965	32231115	32231604
ENSE00003460147	32222538	32222630
ENSE00003471640	32226171	32226320
ENSE00003501085	32228727	32228816
ENSE00003543831	32229135	32229208
ENSE00003573049	32228499	32228609
ENSE00003621377	32224410	32224475
ENSE00003653214	32226403	32226530
ENSE00003667101	32224034	32224121
ENSE00003907454	32222407	32222444

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 98.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 106.1870 / max 709.1135, expressed in 1823 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
1962	92.7546	1823
1963	13.4324	1787

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	98.92	gold quality
ganglionic eminence	UBERON:0004023	98.78	gold quality
smooth muscle tissue	UBERON:0001135	98.69	gold quality
rectum	UBERON:0001052	98.63	gold quality
gastrocnemius	UBERON:0001388	98.63	gold quality
left adrenal gland	UBERON:0001234	98.59	gold quality
right adrenal gland	UBERON:0001233	98.57	gold quality
ventricular zone	UBERON:0003053	98.55	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.53	gold quality
left adrenal gland cortex	UBERON:0035825	98.52	gold quality
stromal cell of endometrium	CL:0002255	98.49	gold quality
right adrenal gland cortex	UBERON:0035827	98.46	gold quality
left ovary	UBERON:0002119	98.45	gold quality
muscle of leg	UBERON:0001383	98.43	gold quality
cortical plate	UBERON:0005343	98.42	gold quality
gall bladder	UBERON:0002110	98.35	gold quality
right ovary	UBERON:0002118	98.30	gold quality
endocervix	UBERON:0000458	98.27	gold quality
body of pancreas	UBERON:0001150	98.27	gold quality
body of stomach	UBERON:0001161	98.25	gold quality
ectocervix	UBERON:0012249	98.22	gold quality
adrenal cortex	UBERON:0001235	98.21	gold quality
left uterine tube	UBERON:0001303	98.21	gold quality
body of uterus	UBERON:0009853	98.19	gold quality
skin of leg	UBERON:0001511	98.18	gold quality
lower esophagus	UBERON:0013473	98.17	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.17	gold quality
adrenal gland	UBERON:0002369	98.15	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.15	gold quality
esophagus	UBERON:0001043	98.12	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-7249	no	3765.48
E-GEOD-93593	no	9.04
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR

miRNA regulators (miRDB)

12 targeting EIF3I, 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-3934-3P	99.76	65.51	1351
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-4677-3P	99.49	67.91	1246
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-660-3P	98.14	66.04	1434
HSA-MIR-6742-3P	97.95	64.50	1490
HSA-MIR-6747-3P	97.73	64.84	1596
HSA-MIR-4474-3P	96.97	65.87	870
HSA-MIR-4485-5P	95.91	59.69	198

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 15)

• eIF3i overexpression fosters the integration of growth signals by mTOR into the mRNA translation process, promoting protein synthesis and tumor growth. (PMID:16929481)
• Subunit b of the eIF3 complex directly binds to HCV IRES domain III via its N-terminal-RRM. (PMID:19059401)
• TGF-beta receptor interacting protein 1 (TRIP-1), which we show inhibits fibroblast collagen contraction, is higher in fetal than adult fibroblasts (PMID:19329541)
• findings report that short hairpin RNA mediated depletion of TRIP-1 gene transcripts in A549 cells promotes epithelial-mesenchymal transition (EMT); knockdown of TRIP-1 dramatically increased A549 responsiveness to TGF-beta1 induction of EMT (PMID:21378021)
• POLR2J interacts with three different subunits of eIF3, eIF3a, eIF3i, and eIF3m. (PMID:22022972)
• eIF3i is a proto-oncogene that drives colon oncogenesis by translationally upregulating COX-2 and activating the beta-catenin signaling pathway (PMID:24056964)
• Clusterin is an independent predictive factor for prognosis of hepatocellular carcinoma and it facilitates metastasis through EIF3I/Akt/MMP13 signaling. (PMID:25609201)
• High eIF3i expression is associated with melanoma. (PMID:28193911)
• EIF3i may affect vesicular stomatitis virus (VSV) growth by regulating the host antiviral response in HeLa cells. (PMID:29173589)
• varying concentrations of TRIP-1 can participate in the nucleation of calcium phosphate polymorphs. (PMID:29745814)
• eIF3i regulation of protein synthesis, cell proliferation, cell cycle progression, and tumorigenesis. (PMID:33301799)
• Insights into the Structure and Function of TRIP-1, a Newly Identified Member in Calcified Tissues. (PMID:36979349)
• eIF3i promotes colorectal cancer cell survival via augmenting PHGDH translation. (PMID:37611825)
• circEIF3I facilitates the recruitment of SMAD3 to early endosomes to promote TGF-beta signalling pathway-mediated activation of MMPs in pancreatic cancer. (PMID:37689715)
• METTL3-mediated m[6]A modification of lncRNA TSPAN12 promotes metastasis of hepatocellular carcinoma through SENP1-depentent deSUMOylation of EIF3I. (PMID:38374407)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	eif3i	ENSDARG00000017445
mus_musculus	Eif3i	ENSMUSG00000028798
rattus_norvegicus	Eif3i	ENSRNOG00000047185
drosophila_melanogaster	eIF3i	FBGN0015834

Protein

Protein identifiers

Eukaryotic translation initiation factor 3 subunit I — Q13347 (reviewed: Q13347)

Alternative names: Eukaryotic translation initiation factor 3 subunit 2, TGF-beta receptor-interacting protein 1, eIF-3-beta, eIF3 p36

All UniProt accessions (28): Q13347, A0A7I2V2M3, A0A7I2V391, A0A7I2V3K6, A0A7I2V3N2, A0A7I2V3T4, A0A7I2V3U3, A0A7I2V415, A0A7I2V4C2, A0A7I2V4S8, A0A7I2V5E4, A0A7I2V5V8, A0A7I2V607, A0A7I2V613, A0A7I2V640, A0A7I2V685, A0A7I2YQC8, A0A7I2YQF8, A0A7I2YQI2, A0A7I2YQI6, A0A7I2YQN1, A0A7I2YQP9, A0A7I2YQT9, A0A7I2YQU2, A0A7I2YQX4, A0A7P0MRT9, Q5TFK1, Q5U0F4

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.

Subcellular location. Cytoplasm.

Post-translational modifications. Phosphorylated by TGF-beta type II receptor.

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

RefSeq proteins (2): NP_001381097, NP_003748* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR019775	WD40_repeat_CS	Conserved_site
IPR027525	eIF3i	Family
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily

Pfam: PF24805

UniProt features (12 total): repeat 7, modified residue 3, chain 1, cross-link 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
6ZP4	ELECTRON MICROSCOPY	2.9
8PJ5	ELECTRON MICROSCOPY	2.9
8PJ6	ELECTRON MICROSCOPY	2.9
6ZON	ELECTRON MICROSCOPY	3
8PJ4	ELECTRON MICROSCOPY	3.2
8PJ1	ELECTRON MICROSCOPY	3.4
8PJ2	ELECTRON MICROSCOPY	3.4
7A09	ELECTRON MICROSCOPY	3.5
8OZ0	ELECTRON MICROSCOPY	3.5
8XXN	ELECTRON MICROSCOPY	3.6
6ZMW	ELECTRON MICROSCOPY	3.7
8PJ3	ELECTRON MICROSCOPY	3.7
6ZVJ	ELECTRON MICROSCOPY	3.8
9BLN	ELECTRON MICROSCOPY	3.9
6YBT	ELECTRON MICROSCOPY	6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13347-F1	92.07	0.83

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 (4): 308, 282, 219, 264

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: 177 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, MORF_DNMT1, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, KAAB_FAILED_HEART_ATRIUM_DN, MODULE_151, ENK_UV_RESPONSE_KERATINOCYTE_UP, MORF_UBE2I, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, MORF_CDK2, GOBP_TRANSLATIONAL_INITIATION, MORF_HDAC2, GOCC_EUKARYOTIC_TRANSLATION_INITIATION_FACTOR_3_COMPLEX, GOMF_TRANSLATION_INITIATION_FACTOR_ACTIVITY, MODULE_149, GOBP_TRANSLATION

GO Biological Process (4): formation of cytoplasmic translation initiation complex (GO:0001732), cytoplasmic translational initiation (GO:0002183), translational initiation (GO:0006413), translation (GO:0006412)

GO Molecular Function (3): RNA binding (GO:0003723), translation initiation factor activity (GO:0003743), protein binding (GO:0005515)

GO Cellular Component (8): cytosol (GO:0005829), eukaryotic translation initiation factor 3 complex (GO:0005852), eukaryotic 43S preinitiation complex (GO:0016282), eukaryotic 48S preinitiation complex (GO:0033290), synapse (GO:0045202), 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	3
cytoplasm	2
cellular anatomical structure	2
cytosolic small ribosomal subunit	2
cytosolic translation preinitiation complex	2
cytoplasmic translational initiation	1
protein-RNA complex assembly	1
cytoplasmic translation	1
formation of translation initiation ternary complex	1
translation	1
metabolic process	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
binding	1
protein-containing complex	1
cell junction	1
extracellular vesicle	1
eukaryotic translation initiation factor 3 complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2718 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EIF3I	EIF3B	P55884	999
EIF3I	EIF3G	O75821	998
EIF3I	EIF3C	Q99613	994
EIF3I	EIF3J	O75822	970
EIF3I	EIF3D	O15371	953
EIF3I	EIF3E	P60228	867
EIF3I	EIF3K	Q9UBQ5	866
EIF3I	EIF3M	Q7L2H7	866
EIF3I	EIF3H	O15372	864
EIF3I	EIF3F	O00303	848
EIF3I	EIF3L	Q9Y262	837
EIF3I	EIF1	P41567	809
EIF3I	CSDE1	O75534	795
EIF3I	EIF4B	P23588	732
EIF3I	EIF5	P55010	718

IntAct

224 interactions, top by confidence:

A	B	Type	Score
EIF3B	EIF3G	psi-mi:“MI:0915”(physical association)	0.930
EIF3B	EIF3G	psi-mi:“MI:0914”(association)	0.930
EIF3B	EIF3F	psi-mi:“MI:0915”(physical association)	0.920
EIF3A	EIF3F	psi-mi:“MI:0915”(physical association)	0.910
EIF3B	EIF3I	psi-mi:“MI:0915”(physical association)	0.830
EIF3G	EIF3I	psi-mi:“MI:0407”(direct interaction)	0.820
EIF3A	EIF3G	psi-mi:“MI:0915”(physical association)	0.800
EIF3G	EIF3F	psi-mi:“MI:0914”(association)	0.730
EIF3D	EIF3F	psi-mi:“MI:0914”(association)	0.730
EIF3J	EIF3B	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
EIF3C	EIF3D	psi-mi:“MI:0915”(physical association)	0.670
HTT	EIF3I	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (462): EIF3I (Affinity Capture-MS), EIF3I (Affinity Capture-MS), EIF3I (Affinity Capture-MS), EIF3B (Affinity Capture-MS), EIF3K (Affinity Capture-MS), HERC2 (Affinity Capture-MS), EIF4G1 (Affinity Capture-MS), EIF3A (Affinity Capture-MS), EIF3H (Affinity Capture-MS), EPB41L1 (Affinity Capture-MS), PRRC2B (Affinity Capture-MS), EIF3F (Affinity Capture-MS), EIF3CL (Affinity Capture-MS), EIF3C (Affinity Capture-MS), EIF3M (Affinity Capture-MS)

ESM2 similar proteins: A1CJY4, A1D7I5, A2QEV8, A3LX18, A4RDD7, A5DGL8, A5DVY3, A6RUL1, A6ZMK5, A7EF03, A7RM20, A7TH19, B0BNA7, B0XYC8, B3MVL6, B3N4C7, B4GSH1, B4JB43, B4KGX9, B4LUA5, B4N0L0, B5FZ19, E3LB80, O02195, P0CS32, P0CS33, P40217, P79083, Q0CXH9, Q13347, Q1DPU4, Q1HPW4, Q29L19, Q2GTM8, Q2UQ34, Q38884, Q4P6E2, Q4WX90, Q5AI86, Q5B8Y3

Diamond homologs: A0AUS0, A0DB19, A0JMQ0, A1CJY4, A1D7I5, A2QEV8, A3LX18, A4H6F7, A4HUV2, A4RDD7, A5DGL8, A5DVY3, A6RUL1, A6ZMK5, A7EF03, A7RM20, A7TH19, A8QBF3, A8WVX8, A8XYW9, A9UZS7, B0BNA7, B0XFT7, B0XYC8, B3MVL6, B3N4C7, B4GIU9, B4GSH1, B4I195, B4JB43, B4KGX9, B4KQU8, B4LUA5, B4MYI5, B4N0L0, B4NW98, B4Q354, B5FZ19, B6K1G6, B8M0Q1

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
EIF3I	up-regulates	TGFBR2	binding
EIF3I	“form complex”	EIF3_complex	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 169 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	20	32.3×	7e-23
Formation of the ternary complex, and subsequently, the 43S complex	17	31.0×	2e-19
Translation initiation complex formation	19	30.6×	2e-21
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	5	28.5×	3e-05
GTP hydrolysis and joining of the 60S ribosomal subunit	22	18.7×	5e-20
L13a-mediated translational silencing of Ceruloplasmin expression	21	18.0×	6e-19
Formation of a pool of free 40S subunits	18	17.1×	1e-15
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	7	16.1×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
formation of cytoplasmic translation initiation complex	13	103.6×	7e-23
translational initiation	17	43.2×	2e-21
stress granule assembly	5	21.3×	5e-04
regulation of translational initiation	6	19.9×	9e-05
protein targeting	5	13.0×	4e-03
cytoplasmic translation	9	11.8×	2e-05
positive regulation of translation	6	9.7×	4e-03
negative regulation of translation	6	8.3×	6e-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	13
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1533 predictions. Top by Δscore:

Variant	Effect	Δscore
1:32221198:C:CC	acceptor_gain	1.0000
1:32222115:T:TA	donor_gain	1.0000
1:32222440:GGATG:G	donor_gain	1.0000
1:32222441:GATGG:G	donor_gain	1.0000
1:32222442:ATGG:A	donor_loss	1.0000
1:32222443:TGGTG:T	donor_loss	1.0000
1:32222445:G:GG	donor_gain	1.0000
1:32222445:GT:G	donor_loss	1.0000
1:32222446:T:A	donor_loss	1.0000
1:32222535:CA:C	acceptor_loss	1.0000
1:32222536:A:AG	acceptor_gain	1.0000
1:32222537:G:GG	acceptor_gain	1.0000
1:32222537:GA:G	acceptor_gain	1.0000
1:32222537:GAA:G	acceptor_gain	1.0000
1:32222631:G:GG	donor_gain	1.0000
1:32224400:A:AG	acceptor_gain	1.0000
1:32226316:GATTG:G	donor_gain	1.0000
1:32226317:A:G	donor_gain	1.0000
1:32226398:CACA:C	acceptor_loss	1.0000
1:32226399:ACAGA:A	acceptor_loss	1.0000
1:32226400:CA:C	acceptor_loss	1.0000
1:32226401:A:AG	acceptor_gain	1.0000
1:32226401:AG:A	acceptor_loss	1.0000
1:32226402:G:GC	acceptor_gain	1.0000
1:32226402:GACA:G	acceptor_gain	1.0000
1:32226402:GACAA:G	acceptor_gain	1.0000
1:32226528:AAGG:A	donor_loss	1.0000
1:32226529:AGGTA:A	donor_loss	1.0000
1:32226531:GT:G	donor_loss	1.0000
1:32226532:T:G	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000097457 (1:32226247 G>A,C), RS1000559671 (1:32222834 C>A,G), RS1000571877 (1:32229450 G>A,C,T), RS1000621551 (1:32221435 A>T), RS1001605814 (1:32223102 C>T), RS1001784433 (1:32235015 C>A,T), RS1001900008 (1:32234650 C>A,T), RS1001918662 (1:32236267 A>C), RS1002027015 (1:32230681 C>G,T), RS1002216917 (1:32233957 T>C), RS1002324796 (1:32234196 G>A), RS1002563095 (1:32225655 C>A,G,T), RS1002597255 (1:32225396 G>A), RS1002637739 (1:32224378 G>A), RS1002846040 (1:32227972 G>A)

Disease associations

OMIM: gene MIM:603911 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Moderate	Autosomal dominant

Mondo (1): complex neurodevelopmental disorder (MONDO:0100038)

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: yes

ChEMBL targets (1): CHEMBL4295814 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.97	Kd	107.9	nM	CHEMBL3752910
6.97	ED50	107.9	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 5 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-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148145: Binding affinity to human EIF3I incubated for 45 mins by Kinobead based pull down assay	kd	0.1079	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	2
sodium arsenite	decreases expression	2
Cyclosporine	increases expression	2
Cadmium Chloride	increases abundance, increases expression, affects reaction, decreases expression	2
TAK-243	increases sumoylation	1
chlorophyllin	decreases expression	1
deoxynivalenol	increases expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects localization, increases expression, affects cotreatment	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
arsenic trichloride	decreases expression, increases abundance	1
CD 437	decreases expression	1
tanespimycin	affects cotreatment, decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
5-(2,4-dihydroxy-5-isopropylphenyl)-4-(4-morpholin-4-ylmethylphenyl)isoxazole-3-carboxylic acid ethylamide	decreases expression	1
STA 9090	decreases expression	1
bisphenol S	increases expression	1
VER 155008	affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	decreases expression, increases abundance	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases methylation	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118682	Binding	Binding affinity to EIF3I in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder