EIF3C

Summary

EIF3C (eukaryotic translation initiation factor 3 subunit C, HGNC:3279) is a protein-coding gene on chromosome 16p11.2, encoding Eukaryotic translation initiation factor 3 subunit C (Q99613). Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis.

Enables ribosome binding activity. Contributes to translation initiation factor activity. Involved in positive regulation of translation and translational initiation. Part of eukaryotic translation initiation factor 3 complex.

Source: NCBI Gene 8663 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 14 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_003752

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3279
Approved symbol	EIF3C
Name	eukaryotic translation initiation factor 3 subunit C
Location	16p11.2
Locus type	gene with protein product
Status	Approved
Aliases	eIF3-p110
Ensembl gene	ENSG00000184110
Ensembl biotype	protein_coding
OMIM	603916
Entrez	8663

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 30 protein_coding, 5 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000331666, ENST00000395587, ENST00000563139, ENST00000564243, ENST00000564839, ENST00000565099, ENST00000565932, ENST00000566086, ENST00000566501, ENST00000566519, ENST00000566866, ENST00000568426, ENST00000569005, ENST00000569690, ENST00000910878, ENST00000910879, ENST00000910880, ENST00000910881, ENST00000910882, ENST00000910883, ENST00000910884, ENST00000910885, ENST00000910886, ENST00000910887, ENST00000910888, ENST00000930031, ENST00000930032, ENST00000930033, ENST00000930034, ENST00000930035, ENST00000966835, ENST00000966836, ENST00000966837, ENST00000966838, ENST00000966839, ENST00000966840

RefSeq mRNA: 5 — MANE Select: NM_003752 NM_001037808, NM_001199142, NM_001267574, NM_001286478, NM_003752

CCDS: CCDS10638, CCDS66993

Canonical transcript exons

ENST00000331666 — 21 exons

Exon	Start	End
ENSE00001297082	28723164	28723323
ENSE00001673265	28714819	28714928
ENSE00001674875	28714321	28714446
ENSE00001766067	28714636	28714690
ENSE00001785177	28715307	28715434
ENSE00002382627	28711657	28711787
ENSE00002601345	28711464	28711518
ENSE00003463163	28735173	28735335
ENSE00003480739	28724322	28724463
ENSE00003491603	28724919	28725012
ENSE00003493042	28734520	28734679
ENSE00003502717	28727021	28727245
ENSE00003519061	28734778	28734843
ENSE00003607973	28731829	28732192
ENSE00003611293	28726605	28726795
ENSE00003644420	28723448	28723551
ENSE00003646704	28713909	28714098
ENSE00003657392	28713701	28713766
ENSE00003659101	28734932	28735019
ENSE00003666792	28724658	28724783
ENSE00003902294	28735431	28735596

Expression profiles

Bgee: expression breadth ubiquitous, 206 present calls, max score 99.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.0330 / max 28.7072, expressed in 1234 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153386	24.6456	1810
153387	2.0330	1234

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	99.44	gold quality
cortical plate	UBERON:0005343	99.39	gold quality
left testis	UBERON:0004533	99.33	gold quality
ganglionic eminence	UBERON:0004023	99.31	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.29	gold quality
lower esophagus mucosa	UBERON:0035834	99.28	gold quality
right lobe of thyroid gland	UBERON:0001119	99.27	gold quality
body of pancreas	UBERON:0001150	99.26	gold quality
right testis	UBERON:0004534	99.23	gold quality
left lobe of thyroid gland	UBERON:0001120	99.22	gold quality
adenohypophysis	UBERON:0002196	99.16	gold quality
left ovary	UBERON:0002119	99.14	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.14	gold quality
mucosa of transverse colon	UBERON:0004991	99.12	gold quality
skin of abdomen	UBERON:0001416	99.10	gold quality
skin of leg	UBERON:0001511	99.09	gold quality
endocervix	UBERON:0000458	99.06	gold quality
ventricular zone	UBERON:0003053	99.06	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.05	gold quality
metanephros cortex	UBERON:0010533	99.04	gold quality
body of stomach	UBERON:0001161	99.03	gold quality
stromal cell of endometrium	CL:0002255	99.01	gold quality
right ovary	UBERON:0002118	98.99	gold quality
anterior cingulate cortex	UBERON:0009835	98.99	gold quality
right frontal lobe	UBERON:0002810	98.93	gold quality
ectocervix	UBERON:0012249	98.92	gold quality
body of uterus	UBERON:0009853	98.89	gold quality
left uterine tube	UBERON:0001303	98.87	gold quality
granulocyte	CL:0000094	98.85	gold quality
right coronary artery	UBERON:0001625	98.85	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	17.08
E-MTAB-6819	no	1443.05

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

20 targeting EIF3C, 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-3617-3P	99.98	67.86	918
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-1228-3P	99.00	66.53	857
HSA-MIR-873-5P	98.84	66.90	1348
HSA-MIR-1199-5P	98.44	66.51	829
HSA-MIR-6751-3P	98.44	66.35	835
HSA-MIR-4660	97.79	67.44	1328
HSA-MIR-4759	97.39	65.86	608
HSA-MIR-134-5P	97.11	66.52	976
HSA-MIR-3118	97.11	66.58	984
HSA-MIR-215-3P	97.02	68.01	1209
HSA-MIR-6759-3P	96.94	68.31	823
HSA-MIR-34A-3P	96.80	67.70	805
HSA-MIR-6854-5P	96.77	65.96	848
HSA-MIR-6857-3P	96.70	65.43	915
HSA-MIR-3117-3P	95.96	67.82	473
HSA-MIR-8083	95.93	67.55	694

Literature-anchored findings (GeneRIF, showing 16)

• These results indicate that the interaction between Hsp90 and eIF3c may play an important role in hepatitis C virus internal ribosome entry site-mediated translation. (PMID:22016036)
• Collectively, eIF3c deletion effectively reduced the survival of colon cancer cells and could be used as a therapeutic tool for colon cancer therapy. (PMID:23733421)
• eukaryotic initiation factor 4G (eIF4G) protein binds to eIF3c, -d, and -e to promote mRNA recruitment to the ribosome. (PMID:24092755)
• eIF3a and eIF3c control abundance and assembly of the entire eIF3 and thus represent its crucial scaffolding elements critically required for formation of preinitiation complexes. (PMID:24912683)
• These findings suggest that eIF3c is overexpressed in human gliomas and essential for their proliferation and survival. (PMID:25823503)
• High eIF3c expression is positively associated with KRAS. (PMID:28231410)
• In EIF3C-positive tumors, 32 out of 42 showed significantly higher frequencies of high grade group by immunoreactivity. (PMID:28854163)
• circ_0067934 promotes cervical cancer progression via miR-545/EIF3C axis. (PMID:30362562)
• EIF3C overexpression was correlated to age and tumor stage in prostate cancer patients and indicated poor survival. The proliferation, migration, and invasiveness of PC3 cells were all inhibited after EIF3C knockdown. Phosphorylation level of PI3K and Akt and total NF-kappaB and Myc decreased after EIF3C knockdown. Therefore, EIF3C at least partially regulates the activity of PI3K/Akt/NF-kappaB signaling pathway in PC3… (PMID:31181967)
• Eukaryotic initiation factor 3, subunit C silencing inhibits cell proliferation and promotes apoptosis in human ovarian cancer cells. (PMID:31316002)
• eIF3C expression was upregulated in renal cell carcinoma (RCC) tissues and cell lines. Depletion of eIF3C reduced tumor cell proliferation and arrested them at the G1 stage, thus promoting their apoptosis in vitro. Depletion of eIF3C also inhibited the formation and growth of tumor cell xenografts in nude mice. Study demonstrated that upregulated eIF3C expression contributed to the development and progression of RCC. (PMID:31638200)
• Whereas the eIF3c knockdown reduces it, downregulation of eIF3k or eIF3l increases mRNA recruitment, suggesting that the latter subunits possess a regulatory potential. Altogether this study provides new insights into the role of human eIF3 in the initial assembly steps of the translational machinery (PMID:31863585)
• ZNF280A promotes lung adenocarcinoma development by regulating the expression of EIF3C. (PMID:33414445)
• Human oncoprotein 5MP suppresses general and repeat-associated non-AUG translation via eIF3 by a common mechanism. (PMID:34260931)
• circPDE5A regulates prostate cancer metastasis via controlling WTAP-dependent N6-methyladenisine methylation of EIF3C mRNA. (PMID:35650605)
• Complement factor H attenuates TNF-alpha-induced inflammation by upregulating EIF3C in rheumatoid arthritis. (PMID:37996918)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	eif3c	ENSDARG00000016443
mus_musculus	Eif3c	ENSMUSG00000030738
rattus_norvegicus	Eif3c	ENSRNOG00000018761
drosophila_melanogaster	eIF3c	FBGN0034258
caenorhabditis_elegans	eif-3.C	WBGENE00001226

Paralogs (1): EIF3CL (ENSG00000205609)

Protein

Protein identifiers

Eukaryotic translation initiation factor 3 subunit C — Q99613 (reviewed: Q99613)

Alternative names: Eukaryotic translation initiation factor 3 subunit 8, eIF3 p110

All UniProt accessions (4): Q99613, H3BPE3, H3BPE4, H3BTY8

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. Identified in a HCV IRES-mediated translation complex, at least composed of EIF3C, IGF2BP1, RPS3 and HCV RNA-replicon. Interacts with ALKBH4, IFIT1 and IFIT2. Interacts with BZW2/5MP1.

Subcellular location. Cytoplasm.

Post-translational modifications. Phosphorylated. Phosphorylation is enhanced upon serum stimulation.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q99613-1	1	yes
Q99613-2	2

RefSeq proteins (5): NP_001032897, NP_001186071, NP_001254503, NP_001273407, NP_003743* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000717	PCI_dom	Domain
IPR008905	EIF3C_N_dom	Domain
IPR027516	EIF3C	Family
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR058999	EIF3CL_C	Domain

Pfam: PF01399, PF05470, PF26569

UniProt features (97 total): helix 39, strand 17, modified residue 15, turn 10, compositionally biased region 7, region of interest 4, sequence conflict 2, chain 1, domain 1, splice variant 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
6YBW	ELECTRON MICROSCOPY	3.1
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
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-Q99613-F1	71.72	0.12

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 (15): 9, 11, 13, 15, 16, 18, 39, 99, 166, 178, 181, 182, 524, 643, 909

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: 124 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, GU_PDEF_TARGETS_DN, ENK_UV_RESPONSE_KERATINOCYTE_UP, MORF_RAD21, HSIAO_HOUSEKEEPING_GENES, GOBP_TRANSLATIONAL_INITIATION, GOCC_EUKARYOTIC_TRANSLATION_INITIATION_FACTOR_3_COMPLEX, GOMF_TRANSLATION_INITIATION_FACTOR_ACTIVITY, MODULE_149, GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, MORF_SKP1A, chr16p11, GOBP_CYTOPLASMIC_TRANSLATIONAL_INITIATION, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION

GO Biological Process (5): formation of cytoplasmic translation initiation complex (GO:0001732), translational initiation (GO:0006413), positive regulation of translation (GO:0045727), cytoplasmic translational initiation (GO:0002183), translation (GO:0006412)

GO Molecular Function (5): RNA binding (GO:0003723), translation initiation factor activity (GO:0003743), translation initiation factor binding (GO:0031369), ribosome binding (GO:0043022), protein binding (GO:0005515)

GO Cellular Component (5): cytosol (GO:0005829), eukaryotic translation initiation factor 3 complex (GO:0005852), eukaryotic 43S preinitiation complex (GO:0016282), eukaryotic 48S preinitiation complex (GO:0033290), 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
translation	2
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
formation of translation initiation ternary complex	1
metabolic process	1
regulation of translation	1
positive regulation of gene expression	1
positive regulation of protein metabolic 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
protein binding	1
ribonucleoprotein complex binding	1
binding	1
protein-containing complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2572 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EIF3C	EIF3B	P55884	999
EIF3C	EIF3G	O75821	998
EIF3C	EIF3E	P60228	995
EIF3C	EIF3I	Q13347	994
EIF3C	EIF3D	O15371	984
EIF3C	EIF3H	O15372	984
EIF3C	EIF3J	O75822	973
EIF3C	EIF3F	O00303	973
EIF3C	EIF3L	Q9Y262	959
EIF3C	EIF1	P41567	904
EIF3C	EIF3K	Q9UBQ5	887
EIF3C	EIF4G1	Q04637	870
EIF3C	EIF5	P55010	853
EIF3C	EIF2S2	P20042	799
EIF3C	EIF3M	Q7L2H7	794

IntAct

231 interactions, top by confidence:

A	B	Type	Score
EIF3M	EIF3F	psi-mi:“MI:0914”(association)	0.960
EIF3G	EIF3B	psi-mi:“MI:0914”(association)	0.930
EIF3F	EIF3B	psi-mi:“MI:0914”(association)	0.920
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:0914”(association)	0.890
EIF3C	EIF3E	psi-mi:“MI:0915”(physical association)	0.810
EIF3E	EIF3C	psi-mi:“MI:0915”(physical association)	0.810
DUSP4	MAPK1	psi-mi:“MI:0914”(association)	0.810
EIF3A	EIF3G	psi-mi:“MI:0915”(physical association)	0.800
EIF3C	EIF3F	psi-mi:“MI:0915”(physical association)	0.800
EIF3A	EIF3C	psi-mi:“MI:0407”(direct interaction)	0.800
EIF3D	EIF3F	psi-mi:“MI:0914”(association)	0.730

BioGRID (477): EIF3C (Affinity Capture-MS), EIF3C (Affinity Capture-MS), EIF3C (Affinity Capture-MS), EIF3C (Affinity Capture-MS), EIF3C (Affinity Capture-MS), EIF3C (Affinity Capture-MS), EIF3C (Affinity Capture-MS), EIF3C (Affinity Capture-MS), EIF3C (Affinity Capture-Western), EIF3C (Affinity Capture-Western), EIF3B (Co-fractionation), EIF3C (Co-fractionation), EIF3C (Co-fractionation), EIF3C (Co-fractionation), EIF3C (Co-fractionation)

ESM2 similar proteins: A0A8I3P7X4, A7S641, A8WG88, A9ULY7, B0R034, B0W6N3, B5DFC8, B5ME19, D6WIX5, E7EXT2, F7AEX0, O60308, O95202, P0C204, P45433, P53569, Q03701, Q0VA06, Q173M7, Q1L987, Q28HX4, Q3SYW6, Q3ZC50, Q4QR58, Q5RAT8, Q5RCI4, Q5U2X6, Q5XGZ8, Q5XIN6, Q5ZK33, Q66I12, Q6AZI2, Q6IVW0, Q6P1V4, Q6PFQ2, Q6PGY6, Q7PGE8, Q7SYB2, Q8BZN6, Q8R1B4

Diamond homologs: A1C987, A1D9P1, A1ZAX1, A3GGB4, A4QSX4, A5DPQ5, A5E3Q2, A6S043, A6ZN26, A7E471, A7TML4, A8WWU0, B0W0S3, B0YEH1, B3MIF1, B3NML0, B4GIB1, B4HMY3, B4J789, B4KN00, B4LNA1, B4MRZ8, B4P562, B5DFC8, B5ME19, O02328, O14164, O49160, P0CN46, P0CN47, P32497, Q0CVT0, Q0V1H5, Q0ZB76, Q17Q06, Q1DP77, Q28Z41, Q2H731, Q2U0Q9, Q3SYW6

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
EIF3C	“form complex”	EIF3_complex	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 156 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	22	39.5×	1e-27
Formation of the ternary complex, and subsequently, the 43S complex	19	38.6×	7e-24
Translation initiation complex formation	21	37.7×	5e-26
GTP hydrolysis and joining of the 60S ribosomal subunit	24	22.7×	3e-24
L13a-mediated translational silencing of Ceruloplasmin expression	23	21.9×	6e-23
Formation of a pool of free 40S subunits	20	21.1×	2e-19
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	7	18.0×	8e-06
Eukaryotic Translation Initiation	5	14.6×	7e-04

GO biological processes:

GO term	Partners	Fold	FDR
formation of cytoplasmic translation initiation complex	14	119.2×	1e-26
translational initiation	20	54.3×	1e-27
regulation of translational initiation	7	24.8×	2e-06
negative regulation of proteasomal ubiquitin-dependent protein catabolic process	5	15.2×	2e-03
cytoplasmic translation	10	14.0×	5e-07
negative regulation of translation	6	8.9×	4e-03
translation	10	7.8×	9e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2825 predictions. Top by Δscore:

Variant	Effect	Δscore
16:28711653:GCA:G	acceptor_loss	1.0000
16:28711656:GGT:G	acceptor_gain	1.0000
16:28711656:GGTCC:G	acceptor_gain	1.0000
16:28711772:GCAAC:G	donor_gain	1.0000
16:28711773:C:T	donor_gain	1.0000
16:28711783:AAACA:A	donor_gain	1.0000
16:28711784:AACA:A	donor_gain	1.0000
16:28711785:ACA:A	donor_gain	1.0000
16:28711786:CA:C	donor_gain	1.0000
16:28711786:CAG:C	donor_loss	1.0000
16:28711788:G:GG	donor_gain	1.0000
16:28713695:A:AG	acceptor_gain	1.0000
16:28713696:A:G	acceptor_gain	1.0000
16:28713699:A:AG	acceptor_gain	1.0000
16:28713699:AG:A	acceptor_gain	1.0000
16:28713699:AGGC:A	acceptor_loss	1.0000
16:28713700:G:GT	acceptor_gain	1.0000
16:28713700:GG:G	acceptor_gain	1.0000
16:28713700:GGC:G	acceptor_gain	1.0000
16:28713700:GGCC:G	acceptor_gain	1.0000
16:28713700:GGCCA:G	acceptor_gain	1.0000
16:28713762:AAGAG:A	donor_loss	1.0000
16:28713763:AGAGG:A	donor_loss	1.0000
16:28713764:GAG:G	donor_gain	1.0000
16:28713765:AGGT:A	donor_loss	1.0000
16:28713767:G:GG	donor_gain	1.0000
16:28713768:T:G	donor_loss	1.0000
16:28713905:CCAG:C	acceptor_loss	1.0000
16:28713906:CAGGT:C	acceptor_loss	1.0000
16:28713907:A:T	acceptor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000487710 (16:28710493 C>G,T), RS1001092220 (16:28694722 C>T), RS1001253504 (16:28692755 G>A,C,T), RS1001347881 (16:28703175 T>A,C), RS1001465565 (16:28700618 GC>G), RS1002356596 (16:28689729 G>C,T), RS1003207410 (16:28730002 A>G), RS1003832750 (16:28730597 T>C), RS1004333241 (16:28712885 C>G,T), RS1004933598 (16:28700529 G>C), RS1005122455 (16:28698579 GCTC>G), RS1005784352 (16:28733959 C>G), RS1007053268 (16:28730803 T>G), RS1007680074 (16:28732863 A>G), RS1008273098 (16:28728164 CT>C,CTT)

Disease associations

OMIM: gene MIM:603916 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST000531_2	Inflammatory bowel disease (early onset)	2.000000e-09
GCST000879_2	Crohn’s disease	2.000000e-11
GCST001725_52	Inflammatory bowel disease	1.000000e-21
GCST004131_83	Inflammatory bowel disease	2.000000e-12
GCST004132_69	Crohn’s disease	3.000000e-10
GCST007044_23	Extremely high intelligence	2.000000e-08
GCST010133_15	Lamb consumption	3.000000e-08
GCST010703_152	Brain morphology (MOSTest)	3.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0008111	diet measurement
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725123 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
7.05	IC50	90	nM	MOLIBRESIB

PubChem BioAssay actives

1 with measured affinity, of 6 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
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178800: Inhibition of EIF3C (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.0900	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, increases expression	2
Cyclosporine	increases methylation, decreases expression	2
chloroacetaldehyde	decreases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
sodium arsenate	decreases expression	1
sodium arsenite	increases stability	1
coumarin	increases phosphorylation	1
methacrylaldehyde	increases abundance, affects cotreatment, increases oxidation	1
CGP 52608	affects binding, increases reaction	1
ICG 001	increases expression	1
abrine	increases expression	1
pyrachlostrobin	decreases expression	1
bisphenol S	increases expression	1
picoxystrobin	decreases expression	1
bisphenol AF	increases expression	1
Arsenic Trioxide	increases expression	1
Cidofovir	decreases expression	1
Acrolein	increases abundance, affects cotreatment, increases oxidation	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Ascorbic Acid	decreases expression	1
Benztropine	decreases expression, affects cotreatment	1
Caffeine	affects phosphorylation	1
Carbamazepine	affects expression	1
Cisplatin	decreases expression	1
Clozapine	affects cotreatment, decreases expression	1
Cuprizone	affects cotreatment, decreases expression	1
Clodronic Acid	decreases expression	1
Diclofenac	affects expression	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	increases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697530	Binding	Inhibition of EIF3C (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Clinical trials (associated diseases)

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