EIF3M

Summary

EIF3M (eukaryotic translation initiation factor 3 subunit M, HGNC:24460) is a protein-coding gene on chromosome 11p13, encoding Eukaryotic translation initiation factor 3 subunit M (Q7L2H7). 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 97.3% of cancer cell lines).

This gene encodes a protein that is part of the eurkaryotic translation initiation factor 3 complete (eIF-3) required for protein synthesis. Elevated levels of the encoded protein are present in cancer cell lines. Inactivation of the encoded protein has been shown to interfere with translation of herpes virus mRNAs by preventing the association of mRNAs with the ribosomes. A pseudogene of this gene is located on the X chromosome.

Source: NCBI Gene 10480 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 51 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 97.3% of screened cell lines (common-essential)
• MANE Select transcript: NM_006360

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24460
Approved symbol	EIF3M
Name	eukaryotic translation initiation factor 3 subunit M
Location	11p13
Locus type	gene with protein product
Status	Approved
Aliases	hfl-B5, FLJ29030, GA17, TANGO7
Ensembl gene	ENSG00000149100
Ensembl biotype	protein_coding
OMIM	609641
Entrez	10480

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 16 protein_coding, 4 nonsense_mediated_decay, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000323213, ENST00000524711, ENST00000524896, ENST00000525054, ENST00000525782, ENST00000526267, ENST00000530026, ENST00000531120, ENST00000531186, ENST00000531921, ENST00000532054, ENST00000532444, ENST00000533439, ENST00000873388, ENST00000873389, ENST00000873390, ENST00000873391, ENST00000924135, ENST00000924136, ENST00000924137, ENST00000924138, ENST00000924139, ENST00000924140, ENST00000924141

RefSeq mRNA: 2 — MANE Select: NM_006360 NM_001307929, NM_006360

CCDS: CCDS76392, CCDS7880

Canonical transcript exons

ENST00000531120 — 11 exons

Exon	Start	End
ENSE00002182985	32602279	32606264
ENSE00002190054	32583831	32583929
ENSE00003461761	32594914	32595013
ENSE00003487651	32589547	32589641
ENSE00003496185	32587012	32587144
ENSE00003546840	32600689	32600832
ENSE00003587893	32588594	32588732
ENSE00003604395	32595966	32596047
ENSE00003648441	32601762	32601822
ENSE00003651945	32593866	32593949
ENSE00003682943	32589012	32589135

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 183.1141 / max 2858.6136, expressed in 1828 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
113628	171.6418	1827
113627	11.0021	1771
113632	0.4702	222

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
germinal epithelium of ovary	UBERON:0001304	99.74	gold quality
superficial temporal artery	UBERON:0001614	99.31	gold quality
parietal pleura	UBERON:0002400	99.30	gold quality
body of pancreas	UBERON:0001150	99.26	gold quality
ganglionic eminence	UBERON:0004023	99.25	gold quality
left ovary	UBERON:0002119	99.24	gold quality
ovary	UBERON:0000992	99.22	gold quality
monocyte	CL:0000576	99.21	gold quality
oral cavity	UBERON:0000167	99.21	gold quality
epithelium of nasopharynx	UBERON:0001951	99.19	gold quality
adrenal tissue	UBERON:0018303	99.16	gold quality
mononuclear cell	CL:0000842	99.15	gold quality
endometrium	UBERON:0001295	99.15	gold quality
leukocyte	CL:0000738	99.14	gold quality
ventricular zone	UBERON:0003053	99.12	gold quality
right ovary	UBERON:0002118	99.11	gold quality
cortical plate	UBERON:0005343	99.08	gold quality
pleura	UBERON:0000977	99.05	gold quality
mucosa of paranasal sinus	UBERON:0005030	99.05	gold quality
penis	UBERON:0000989	99.03	gold quality
right adrenal gland	UBERON:0001233	99.03	gold quality
body of uterus	UBERON:0009853	99.03	gold quality
right adrenal gland cortex	UBERON:0035827	99.03	gold quality
left adrenal gland	UBERON:0001234	99.00	gold quality
adrenal cortex	UBERON:0001235	99.00	gold quality
lymph node	UBERON:0000029	98.99	gold quality
endocervix	UBERON:0000458	98.97	gold quality
adrenal gland	UBERON:0002369	98.97	gold quality
left adrenal gland cortex	UBERON:0035825	98.97	gold quality
gingival epithelium	UBERON:0001949	98.95	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-124472	yes	2285.51
E-GEOD-114530	yes	1917.93
E-HCAD-10	yes	1721.92
E-HCAD-1	yes	11.08
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ZIC1

miRNA regulators (miRDB)

53 targeting EIF3M, 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-3924	100.00	72.09	2394
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-520D-3P	99.83	70.78	1676
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-199A-3P	99.75	70.48	929
HSA-MIR-199B-3P	99.75	70.48	929
HSA-MIR-3129-5P	99.75	70.46	914
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-379-3P	99.69	69.60	1524
HSA-MIR-411-3P	99.69	69.63	1524
HSA-MIR-298	99.63	67.56	1916

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 97.3% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 6)

• Cloned a previously uncharacterized human gene, designated hfl-B5, and showed that it encodes a type II cell surface membrane protein that can serve as a receptor for entry of HSV. (PMID:15919898)
• Concluded that the C terminus of B5 contains a functional region that is important for the B5 receptor to mediate events in HSV entry. (PMID:15919899)
• the human Tango7 counterpart, PCID1 (also known as EIF3M), impinged on caspase 9, revealing a new regulatory axis affecting the apoptosome (PMID:19483676)
• Results demonstrate that B5 plays a major role in the initiation of HSV protein translation and could provide a novel target for strategies to prevent primary and recurrent herpetic disease. (PMID:20676407)
• eIF3m mediates regulation of tumorigenesis-related genes in human colon cancer (PMID:20838379)
• POLR2J interacts with three different subunits of eIF3, eIF3a, eIF3i, and eIF3m. (PMID:22022972)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	eif3m	ENSDARG00000013931
mus_musculus	Eif3m	ENSMUSG00000027170
rattus_norvegicus	Eif3m	ENSRNOG00000012738
drosophila_melanogaster	eIF3m	FBGN0033902
caenorhabditis_elegans		WBGENE00019543

Paralogs (2): COPS7A (ENSG00000111652), COPS7B (ENSG00000144524)

Protein

Protein identifiers

Eukaryotic translation initiation factor 3 subunit M — Q7L2H7 (reviewed: Q7L2H7)

Alternative names: Fetal lung protein B5, PCI domain-containing protein 1

All UniProt accessions (8): Q7L2H7, E7ESM3, E9PN86, E9PRI2, E9PRY0, E9PSB3, H0YCQ8, J3KNJ2

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. (Microbial infection) May favor virus entry in case of infection with herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2).

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.

Tissue specificity. Broadly expressed.

Induction. By glucose deprivation in neuroblastoma cells.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q7L2H7-1	1	yes
Q7L2H7-2	2

RefSeq proteins (2): NP_001294858, NP_006351* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000717	PCI_dom	Domain
IPR016024	ARM-type_fold	Homologous_superfamily
IPR027528	eIF3m	Family
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR040750	eIF3m_C_helix	Domain
IPR045237	COPS7/eIF3m	Family

Pfam: PF01399, PF18005

UniProt features (69 total): helix 19, turn 14, strand 12, sequence conflict 7, modified residue 5, mutagenesis site 4, sequence variant 3, initiator methionine 1, chain 1, domain 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

28 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
6FEC	ELECTRON MICROSCOPY	6.3
3J8B	ELECTRON MICROSCOPY	9.3
3J8C	ELECTRON MICROSCOPY	11.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7L2H7-F1	55.33	0.00

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 (5): 2, 2, 152, 254, 367

Mutagenesis-validated functional residues (4):

Position	Phenotype
350	reduces hsv binding and entry.
354	reduces hsv binding and entry.
361	reduces hsv binding and entry.
364	reduces hsv binding and entry.

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: 147 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, MODULE_151, MORF_UBE2I, MORF_HDAC1, GOBP_TRANSLATIONAL_INITIATION, MORF_HDAC2, GOCC_EUKARYOTIC_TRANSLATION_INITIATION_FACTOR_3_COMPLEX, GOMF_TRANSLATION_INITIATION_FACTOR_ACTIVITY, PUJANA_CHEK2_PCC_NETWORK, GOBP_TRANSLATION, OSWALD_HEMATOPOIETIC_STEM_CELL_IN_COLLAGEN_GEL_UP, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, GOBP_CYTOPLASMIC_TRANSLATIONAL_INITIATION, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION

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): translation initiation factor activity (GO:0003743), translation initiation factor binding (GO:0031369), protein binding (GO:0005515)

GO Cellular Component (7): cytosol (GO:0005829), eukaryotic translation initiation factor 3 complex (GO:0005852), eukaryotic 43S preinitiation complex (GO:0016282), eukaryotic 48S preinitiation complex (GO:0033290), eukaryotic translation initiation factor 3 complex, eIF3m (GO:0071541), cytoplasm (GO:0005737), protein-containing complex (GO:0032991)

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
translation factor activity	1
protein binding	1
binding	1
protein-containing complex	1
eukaryotic translation initiation factor 3 complex	1
intracellular anatomical structure	1
cellular_component	1

Protein interactions and networks

STRING

2091 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EIF3M	EIF3E	P60228	951
EIF3M	EIF3B	P55884	928
EIF3M	DEPDC7	Q96QD5	926
EIF3M	EIF3D	O15371	901
EIF3M	EIF3F	O00303	887
EIF3M	EIF3H	O15372	871
EIF3M	EIF3I	Q13347	866
EIF3M	EIF3K	Q9UBQ5	865
EIF3M	EIF3L	Q9Y262	855
EIF3M	EIF3J	O75822	826
EIF3M	CSTF3	Q12996	816
EIF3M	EIF3C	Q99613	794
EIF3M	EIF3A	Q14152	771
EIF3M	DIAPH1	O60610	767
EIF3M	EIF4G1	Q04637	747

IntAct

216 interactions, top by confidence:

A	B	Type	Score
EIF3F	EIF3M	psi-mi:“MI:0915”(physical association)	0.960
EIF3M	EIF3F	psi-mi:“MI:0915”(physical association)	0.960
EIF3F	EIF3M	psi-mi:“MI:0407”(direct interaction)	0.960
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
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
EIF3H	EIF3F	psi-mi:“MI:0914”(association)	0.890
EIF3F	EIF3H	psi-mi:“MI:0915”(physical association)	0.890
EIF3F	EIF3H	psi-mi:“MI:0914”(association)	0.890
EIF3H	EIF3M	psi-mi:“MI:0407”(direct interaction)	0.870
EIF3C	EIF3F	psi-mi:“MI:0915”(physical association)	0.800

BioGRID (361): EIF3M (Affinity Capture-MS), EIF3M (Affinity Capture-MS), EIF3M (Affinity Capture-MS), EIF3M (Affinity Capture-MS), EIF3M (Affinity Capture-MS), EIF3M (Affinity Capture-MS), EIF3K (Affinity Capture-MS), EIF3B (Affinity Capture-MS), EIF3A (Affinity Capture-MS), EIF3CL (Affinity Capture-MS), EIF3C (Affinity Capture-MS), EIF3L (Affinity Capture-MS), EIF3D (Affinity Capture-MS), EIF3E (Affinity Capture-MS), USP34 (Affinity Capture-MS)

ESM2 similar proteins: A1CKN7, A1D6T6, A5A6M4, A5AAA4, A7RWP6, B0WAM5, B0WR18, B0XXL3, B3M4D9, B3NDH5, B4HK67, B4IXG1, B4KY00, B4PK98, B4QMY7, O00232, O49160, O77410, P45432, Q0CNR3, Q1E170, Q1HQY6, Q2F5R8, Q2HJG5, Q2UKS9, Q3T148, Q3ZCK1, Q4WY08, Q5M7J9, Q5R8C4, Q5RBI3, Q5ZJ64, Q6DK91, Q6INS3, Q6P878, Q7L2H7, Q7QIL8, Q7T2A5, Q7T3B0, Q8AVJ0

Diamond homologs: A7SPX9, A8WQY8, B0WTN3, B3MCZ5, B3NRC6, B4GDM5, B4HR14, B4JW83, B4KT65, B4LJT9, B4MY75, B4P6M6, B4QFD2, Q17D30, Q292F0, Q3T148, Q5DHT6, Q5R8C4, Q5ZJ64, Q6DK91, Q7JVI3, Q7L2H7, Q7Q068, Q7T3B0, Q7ZYU8, Q94261, Q99JX4, Q9V4S8, Q7SEK1, Q94JU3, B0BN93, Q9UNM6, Q9WVJ2, Q0UXJ7, Q09722

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
EIF3M	“form complex”	EIF3_complex	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 146 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	38.1×	1e-27
Translation initiation complex formation	21	36.3×	5e-26
Formation of the ternary complex, and subsequently, the 43S complex	18	35.3×	6e-22
GTP hydrolysis and joining of the 60S ribosomal subunit	27	24.6×	4e-28
L13a-mediated translational silencing of Ceruloplasmin expression	26	23.9×	4e-27
Formation of a pool of free 40S subunits	22	22.4×	4e-22
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	8	19.8×	2e-07
Eukaryotic Translation Initiation	5	14.0×	7e-04

GO biological processes:

GO term	Partners	Fold	FDR
formation of cytoplasmic translation initiation complex	14	121.9×	8e-27
translational initiation	20	55.6×	8e-28
regulation of translational initiation	8	29.0×	5e-08
cytoplasmic translation	12	17.2×	1e-09
negative regulation of proteasomal ubiquitin-dependent protein catabolic process	5	15.6×	1e-03
negative regulation of translation	9	13.7×	3e-06
positive regulation of translation	7	12.4×	1e-04
ribosomal small subunit biogenesis	6	10.6×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2217 predictions. Top by Δscore:

Variant	Effect	Δscore
11:32583928:AGGT:A	donor_loss	1.0000
11:32583929:GGTG:G	donor_loss	1.0000
11:32583930:G:GA	donor_loss	1.0000
11:32587140:TAAAG:T	donor_loss	1.0000
11:32587141:AAAGG:A	donor_loss	1.0000
11:32587142:AAG:A	donor_loss	1.0000
11:32587143:AGGTT:A	donor_loss	1.0000
11:32587146:T:A	donor_loss	1.0000
11:32588588:GTGTA:G	acceptor_loss	1.0000
11:32588589:TGTA:T	acceptor_loss	1.0000
11:32588591:TAGAT:T	acceptor_loss	1.0000
11:32588592:A:AG	acceptor_gain	1.0000
11:32588592:A:G	acceptor_loss	1.0000
11:32588593:G:A	acceptor_loss	1.0000
11:32588593:G:GG	acceptor_gain	1.0000
11:32588593:GAT:G	acceptor_gain	1.0000
11:32588728:CAGTT:C	donor_gain	1.0000
11:32588730:GTT:G	donor_gain	1.0000
11:32588731:TT:T	donor_gain	1.0000
11:32588733:G:GG	donor_gain	1.0000
11:32588738:T:G	donor_gain	1.0000
11:32589136:G:GG	donor_gain	1.0000
11:32589652:G:GG	donor_gain	1.0000
11:32593864:A:AG	acceptor_gain	1.0000
11:32593864:AGT:A	acceptor_gain	1.0000
11:32593865:G:GG	acceptor_gain	1.0000
11:32593865:GT:G	acceptor_gain	1.0000
11:32593865:GTG:G	acceptor_gain	1.0000
11:32593865:GTGA:G	acceptor_gain	1.0000
11:32593865:GTGAT:G	acceptor_gain	1.0000

AlphaMissense

2490 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:32588614:A:C	S66R	1.000
11:32588616:T:A	S66R	1.000
11:32588616:T:G	S66R	1.000
11:32593943:C:A	A204D	1.000
11:32594982:T:A	V229D	1.000
11:32595967:T:C	L240P	1.000
11:32602298:T:C	F342L	1.000
11:32602300:T:A	F342L	1.000
11:32602300:T:G	F342L	1.000
11:32583903:T:C	F6L	0.999
11:32583905:C:A	F6L	0.999
11:32583905:C:G	F6L	0.999
11:32587022:T:C	L18P	0.999
11:32589023:T:C	L109P	0.999
11:32593898:T:A	L189H	0.999
11:32593898:T:C	L189P	0.999
11:32593922:C:A	A197D	0.999
11:32593942:G:C	A204P	0.999
11:32594915:T:C	C207R	0.999
11:32594919:T:A	I208N	0.999
11:32594964:T:C	L223P	0.999
11:32594979:C:A	P228Q	0.999
11:32594979:C:G	P228R	0.999
11:32594987:T:C	F231L	0.999
11:32594989:T:A	F231L	0.999
11:32594989:T:G	F231L	0.999
11:32594991:T:C	L232S	0.999
11:32594991:T:G	L232W	0.999
11:32596011:T:C	F255L	0.999
11:32596012:T:C	F255S	0.999

dbSNP variants (sampled 300 via entrez): RS1000023858 (11:32596733 C>G), RS1000138077 (11:32596445 A>G), RS1000272589 (11:32593103 G>C,T), RS1000371320 (11:32583608 G>A), RS1000401164 (11:32600358 T>C), RS1000444654 (11:32589374 C>G), RS1000464155 (11:32592004 A>C), RS1000570648 (11:32601028 C>A,G), RS1000577623 (11:32594191 G>C), RS1000950318 (11:32583114 G>A), RS1001012039 (11:32594639 T>C), RS1001068880 (11:32588408 A>G), RS1001138069 (11:32582477 T>C,G), RS1001260207 (11:32601107 T>A), RS1001329089 (11:32595467 C>A,G,T)

Disease associations

OMIM: gene MIM:609641 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005312_51	Menopause (age at onset)	3.000000e-09
GCST012295_16	Schizophrenia, bipolar disorder or recurrent major depressive disorder x sex interaction	1.000000e-05

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004704	age at menopause
EFO:0004952	disease recurrence
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725006 (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
7.30	Kd	50.3	nM	CHEMBL5653589
7.30	ED50	50.3	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 8 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	2148140: Binding affinity to human EIF3M incubated for 45 mins by Kinobead based pull down assay	kd	0.0503	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression, affects expression	4
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
Arsenic	affects cotreatment, increases abundance, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
FR900359	affects phosphorylation	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
sodium arsenate	decreases expression	1
trichostatin A	increases expression	1
arsenite	affects binding, increases reaction	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
chloropicrin	increases expression	1
entinostat	decreases expression	1
K 7174	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
bisphenol S	increases expression	1
jinfukang	decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Temozolomide	increases expression	1
Arsenic Trioxide	increases expression	1
Panobinostat	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	increases expression	1
Cadmium	increases abundance, increases expression	1
Caffeine	increases phosphorylation	1
Clozapine	affects cotreatment, increases expression	1
Cuprizone	affects cotreatment, increases expression	1
Demecolcine	increases expression	1
Diethylstilbestrol	increases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651182	Binding	Binding affinity to human EIF3M 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.