EIF4G3

Summary

EIF4G3 (eukaryotic translation initiation factor 4 gamma 3, HGNC:3298) is a protein-coding gene on chromosome 1p36.12, encoding Eukaryotic translation initiation factor 4 gamma 3 (O43432). Component of the protein complex eIF4F, which is involved in the recognition of the mRNA cap, ATP-dependent unwinding of 5’-terminal secondary structure and recruitment of mRNA to the ribosome.

The protein encoded by this gene is thought to be part of the eIF4F protein complex, which is involved in mRNA cap recognition and transport of mRNAs to the ribosome. Interestingly, a microRNA (miR-520c-3p) has been found that negatively regulates synthesis of the encoded protein, and this leads to a global decrease in protein translation and cell proliferation. Therefore, this protein is a key component of the anti-tumor activity of miR-520c-3p.

Source: NCBI Gene 8672 — RefSeq curated summary.

At a glance

• GWAS associations: 18
• Clinical variants (ClinVar): 236 total — 1 likely-pathogenic
• MANE Select transcript: NM_001391906

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3298
Approved symbol	EIF4G3
Name	eukaryotic translation initiation factor 4 gamma 3
Location	1p36.12
Locus type	gene with protein product
Status	Approved
Aliases	eIF4GII
Ensembl gene	ENSG00000075151
Ensembl biotype	protein_coding
OMIM	603929
Entrez	8672

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 14 protein_coding, 4 nonsense_mediated_decay, 4 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000264211, ENST00000356916, ENST00000374933, ENST00000374935, ENST00000400422, ENST00000411888, ENST00000435383, ENST00000438975, ENST00000463775, ENST00000476088, ENST00000485722, ENST00000602326, ENST00000634778, ENST00000634879, ENST00000681717, ENST00000681767, ENST00000682284, ENST00000684485, ENST00000685814, ENST00000685872, ENST00000686579, ENST00000688741, ENST00000693470

RefSeq mRNA: 20 — MANE Select: NM_001391906 NM_001198801, NM_001198802, NM_001198803, NM_001391892, NM_001391893, NM_001391894, NM_001391895, NM_001391896, NM_001391897, NM_001391898, NM_001391899, NM_001391900, NM_001391901, NM_001391902, NM_001391903, NM_001391904, NM_001391905, NM_001391906, NM_001391907, NM_003760

CCDS: CCDS214, CCDS55580, CCDS59192, CCDS72723, CCDS90875, CCDS90876

Canonical transcript exons

ENST00000602326 — 37 exons

Exon	Start	End
ENSE00001066154	20973002	20973099
ENSE00001419647	20997601	20997633
ENSE00001465226	21001199	21001312
ENSE00001465229	21176175	21176358
ENSE00001542805	20806479	20807500
ENSE00001594127	20879323	20879520
ENSE00001604127	20862228	20862332
ENSE00001604595	20813158	20813239
ENSE00001658251	20865116	20865262
ENSE00001672406	20817392	20817538
ENSE00001683487	20810738	20810884
ENSE00001686750	20950003	20950111
ENSE00001690105	20886201	20886371
ENSE00001690531	20849415	20849530
ENSE00001703965	20864476	20864712
ENSE00001712596	20854978	20855071
ENSE00001726513	20853560	20853677
ENSE00001764077	20860385	20860517
ENSE00001784396	20851258	20851478
ENSE00001804546	20857403	20857497
ENSE00002176939	20825100	20825198
ENSE00002247070	20982388	20982408
ENSE00003227684	21050866	21050994
ENSE00003235835	21089138	21089213
ENSE00003337316	21002713	21002808
ENSE00003457551	21176722	21176897
ENSE00003472324	20895368	20895501
ENSE00003477705	20980334	20980448
ENSE00003484684	20827617	20827698
ENSE00003489381	20893517	20893636
ENSE00003490165	20899697	20899943
ENSE00003564924	20829147	20829272
ENSE00003613920	20941491	20942330
ENSE00003618120	20904883	20904971
ENSE00003647587	20981048	20981227
ENSE00003683156	20840856	20841028
ENSE00003789229	20969474	20969596

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.24.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 72.6450 / max 1100.7359, expressed in 1825 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
10814	69.8979	1825
10813	1.0960	660
10804	0.8666	542
10803	0.4183	204
10802	0.1899	48
10815	0.1652	33
10816	0.0110	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.24	gold quality
male germ cell	CL:0000015	97.99	gold quality
choroid plexus epithelium	UBERON:0003911	97.80	gold quality
right testis	UBERON:0004534	96.36	gold quality
left testis	UBERON:0004533	96.34	gold quality
frontal pole	UBERON:0002795	96.30	gold quality
Brodmann (1909) area 10	UBERON:0013541	96.25	gold quality
testis	UBERON:0000473	95.98	gold quality
ventricular zone	UBERON:0003053	95.70	gold quality
cortical plate	UBERON:0005343	95.04	gold quality
colonic epithelium	UBERON:0000397	94.90	gold quality
lateral nuclear group of thalamus	UBERON:0002736	94.14	gold quality
middle frontal gyrus	UBERON:0002702	93.94	gold quality
primary visual cortex	UBERON:0002436	93.92	gold quality
stromal cell of endometrium	CL:0002255	93.84	gold quality
postcentral gyrus	UBERON:0002581	93.83	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.75	gold quality
prefrontal cortex	UBERON:0000451	93.71	gold quality
ganglionic eminence	UBERON:0004023	93.64	gold quality
adrenal tissue	UBERON:0018303	93.61	gold quality
Brodmann (1909) area 23	UBERON:0013554	93.55	gold quality
parietal lobe	UBERON:0001872	93.27	gold quality
superior frontal gyrus	UBERON:0002661	93.18	gold quality
entorhinal cortex	UBERON:0002728	93.18	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	93.01	gold quality
CA1 field of hippocampus	UBERON:0003881	92.97	gold quality
medial globus pallidus	UBERON:0002477	92.96	gold quality
occipital lobe	UBERON:0002021	92.82	gold quality
frontal cortex	UBERON:0001870	92.72	gold quality
islet of Langerhans	UBERON:0000006	92.71	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.08

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): DEAF1

miRNA regulators (miRDB)

76 targeting EIF4G3, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-6757-3P	99.63	66.88	1089
HSA-MIR-567	99.63	68.57	1219
HSA-MIR-106A-3P	99.53	67.58	995
HSA-MIR-7159-3P	99.51	70.17	1920
HSA-MIR-548AV-3P	99.43	68.50	1721
HSA-MIR-4666A-5P	99.41	69.72	1887

Literature-anchored findings (GeneRIF, showing 1)

• Our study demonstrates that circ-EIF4G3 promotes the proliferation, invasion and migration of gastric cancer via sponging miR-335. (PMID:31257089)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	eif4g3b	ENSDARG00000074331
danio_rerio	eif4g3a	ENSDARG00000077215
mus_musculus	Eif4g3	ENSMUSG00000028760
rattus_norvegicus	Eif4g3	ENSRNOG00000014368

Paralogs (2): EIF4G2 (ENSG00000110321), EIF4G1 (ENSG00000114867)

Protein

Protein identifiers

Eukaryotic translation initiation factor 4 gamma 3 — O43432 (reviewed: O43432)

Alternative names: eIF-4-gamma II

All UniProt accessions (14): O43432, A0A0A0MSA7, A0A0U1RQK7, A0A7P0T858, A0A7P0TB42, A0A7P0TBQ8, A0A804HJV5, A0A8I5KT99, A0A8I5KV92, A0A8I5QJH9, A0A8I5QKZ5, A0A8J9G7U8, B1AN91, B1AN92

UniProt curated annotations — full annotation on UniProt →

Function. Component of the protein complex eIF4F, which is involved in the recognition of the mRNA cap, ATP-dependent unwinding of 5’-terminal secondary structure and recruitment of mRNA to the ribosome. Functional homolog of EIF4G1.

Subunit / interactions. Interacts with EIF4A, EIF4E, eIF3 and PABPC1. Part of a complex with EIF4E. eIF4F is a multi-subunit complex, the composition of which varies with external and internal environmental conditions. It is composed of at least EIF4A, EIF4E and EIF4G1/EIF4G3. EIF4G1/EIF4G3 interacts through its C-terminus with the serine/threonine kinases MKNK1, and with MKNK2. Appears to act as a scaffold protein, holding these enzymes in place to phosphorylate eIF4E. Non-phosphorylated EIF4EBP1 competes with EIF4G1/EIFG3 to interact with EIF4E; insulin stimulated MAP-kinase (MAPK1 and MAPK3) phosphorylation of EIF4EBP1 causes dissociation of the complex allowing EIF4G1/EIF4G3 to bind and consequent initiation of translation. EIF4G1/EIF4G3 interacts with PABPC1 to bring about circularization of the mRNA. Interacts with FXR1; promoting translation of FXR1 target mRNAs.

Post-translational modifications. Following infection by certain enteroviruses, rhinoviruses and aphthoviruses, EIF4G1 is cleaved by the viral protease 2A, or the leader protease in the case of aphthoviruses. This shuts down the capped cellular mRNA transcription.

Similarity. Belongs to the eukaryotic initiation factor 4G family.

Isoforms (4)

UniProt ID	Names	Canonical?
O43432-1	1	yes
O43432-2	2
O43432-3	3
O43432-4	4

RefSeq proteins (20): NP_001185730, NP_001185731, NP_001185732, NP_001378821, NP_001378822, NP_001378823, NP_001378824, NP_001378825, NP_001378826, NP_001378827, NP_001378828, NP_001378829, NP_001378830, NP_001378831, NP_001378832, NP_001378833, NP_001378834, NP_001378835, NP_001378836, NP_003751 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003307	W2_domain	Domain
IPR003890	MIF4G-like_typ-3	Domain
IPR003891	Initiation_fac_eIF4g_MI	Domain
IPR016024	ARM-type_fold	Homologous_superfamily

Pfam: PF02020, PF02847, PF02854

UniProt features (78 total): region of interest 15, helix 11, compositionally biased region 10, modified residue 9, splice variant 6, mutagenesis site 6, repeat 5, domain 3, sequence variant 3, turn 3, coiled-coil region 2, site 2, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1HU3	X-RAY DIFFRACTION	2.37

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43432-F1	56.22	0.11

Functional residue map

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

Catalytic / active sites (2): 699–700 (cleavage; by enterovirus/rhinovirus protease 2a); 700–701 (cleavage; by foot-and-mouth disease virus leader protease)

Post-translational modifications (9): 168, 230, 232, 267, 441, 495, 1156, 1218, 1409

Mutagenesis-validated functional residues (6):

Position	Phenotype
756	reduces binding to eif4a; when associated with d-759 and d-764.
759	reduces binding to eif4a; when associated with d-756 and d-764.
764	reduces binding to eif4a; when associated with d-756 and d-759.
814	reduces binding to eif4a; when associated with d-820.
820	reduces binding to eif4a; when associated with d-814.
834–835	reduces binding to ires.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-1169408	ISG15 antiviral mechanism
R-HSA-9918487	Dengue Virus Genome Translation and Replication

MSigDB gene sets: 225 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GOBP_REGULATION_OF_AUTOPHAGY, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_TRANSLATIONAL_INITIATION, GOBP_MALE_GAMETE_GENERATION, GOMF_TRANSLATION_INITIATION_FACTOR_ACTIVITY, GOBP_TRANSLATION, GOBP_NEGATIVE_REGULATION_OF_AUTOPHAGY, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, KEGG_VIRAL_MYOCARDITIS, ONKEN_UVEAL_MELANOMA_UP, HUTTMANN_B_CLL_POOR_SURVIVAL_DN, WANG_LMO4_TARGETS_DN, GOBP_REGULATION_OF_CATABOLIC_PROCESS, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN

GO Biological Process (6): translational initiation (GO:0006413), regulation of translational initiation (GO:0006446), spermatid development (GO:0007286), positive regulation of translation (GO:0045727), translation (GO:0006412), regulation of translation (GO:0006417)

GO Molecular Function (6): RNA cap binding (GO:0000339), RNA binding (GO:0003723), mRNA binding (GO:0003729), translation initiation factor activity (GO:0003743), translation factor activity, RNA binding (GO:0008135), protein binding (GO:0005515)

GO Cellular Component (3): cytoplasm (GO:0005737), cytosol (GO:0005829), eukaryotic translation initiation factor 4F complex (GO:0016281)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Antimicrobial mechanism of IFN-stimulated genes	1
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
translation	4
translational initiation	3
RNA binding	3
regulation of translation	2
translation factor activity	2
cellular anatomical structure	2
cytoplasm	2
formation of translation initiation ternary complex	1
metabolic process	1
germ cell development	1
spermatid differentiation	1
positive regulation of gene expression	1
positive regulation of protein metabolic process	1
peptidyltransferase activity	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
nucleic acid binding	1
binding	1
intracellular anatomical structure	1
RNA cap binding complex	1

Protein interactions and networks

STRING

2338 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EIF4G3	EIF4A1	P04765	999
EIF4G3	EIF4A2	Q14240	998
EIF4G3	EIF4E	P06730	993
EIF4G3	PABPC1	P11940	984
EIF4G3	EIF4E2	O60573	950
EIF4G3	EIF4E3	Q8N5X7	785
EIF4G3	MKNK1	Q9BUB5	768
EIF4G3	EIF3D	O15371	748
EIF4G3	EIF4B	P23588	695
EIF4G3	EIF4A3	P38919	659
EIF4G3	EIF5	P55010	609
EIF4G3	EIF4EBP2	Q13542	590
EIF4G3	PABPN1	Q86U42	573
EIF4G3	EIF1	P41567	542
EIF4G3	ATP7A	Q04656	531

IntAct

125 interactions, top by confidence:

A	B	Type	Score
EIF4E	EIF4G3	psi-mi:“MI:0914”(association)	0.810
EIF4A1	EIF4G3	psi-mi:“MI:0914”(association)	0.800
QPRT	PIK3C2A	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
EIF4E	RNMT	psi-mi:“MI:0407”(direct interaction)	0.630
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAG	SHTN1	psi-mi:“MI:0914”(association)	0.560
PABPC1	EIF4G3	psi-mi:“MI:0407”(direct interaction)	0.540
PABPC1	EIF4G3	psi-mi:“MI:0915”(physical association)	0.540
EPHA1	EXOC5	psi-mi:“MI:0914”(association)	0.530
EIF4A1	EIF3D	psi-mi:“MI:0914”(association)	0.530
COMTD1	IFRD1	psi-mi:“MI:0914”(association)	0.530
NFATC2IP	ZNHIT1	psi-mi:“MI:0914”(association)	0.530
HAO2	EIF4G3	psi-mi:“MI:0914”(association)	0.530
KPTN	EIF4G3	psi-mi:“MI:0914”(association)	0.530
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
YES1	EIF4G3	psi-mi:“MI:0407”(direct interaction)	0.440
EIF4G3	PKM	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
NCBP1	EIF4G3	psi-mi:“MI:0915”(physical association)	0.400
EIF4G3	HSPB1	psi-mi:“MI:0915”(physical association)	0.370
MKNK1	EIF4G3	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (202): EIF4G3 (Affinity Capture-MS), EIF4G3 (Affinity Capture-MS), EIF4G3 (Affinity Capture-MS), EIF4G3 (Affinity Capture-MS), EIF4G3 (Affinity Capture-MS), EIF4G3 (Affinity Capture-MS), EIF4G3 (Affinity Capture-MS), EIF4G3 (Affinity Capture-MS), EIF4G3 (Affinity Capture-MS), EIF4G3 (Two-hybrid), EIF4G3 (Co-fractionation), EIF4G3 (Co-fractionation), EIF4G3 (Co-fractionation), PABPC1 (Co-fractionation), PABPC4 (Co-fractionation)

ESM2 similar proteins: A0A0K3AV08, A0A1L8H8C0, A0A1L8HFX9, A0A2R6X6S3, A1ZA92, A2RUV4, A8DYP0, F1QIC4, G5EBZ8, G5ECQ3, M9MRD1, M9PGC5, O43432, O43491, O61366, O93383, O95819, P11171, P34643, P41993, P83510, P97868, Q02645, Q09446, Q0KIC3, Q11181, Q17353, Q24546, Q5DTJ9, Q69ZW3, Q6DFG0, Q71M21, Q7YZA2, Q86TC9, Q86UR5, Q8NDI1, Q8STF6, Q925Q9, Q96PY6, Q99NE5

Diamond homologs: A0A1S3C4H6, A9Z1V5, B9FXV5, C7G046, G5CEW6, O43432, P41110, Q03387, Q04637, Q41583, Q54DU5, Q54DV3, Q54MG1, Q54MG4, Q5TIE3, Q6K641, Q6NZJ6, Q76E23, Q80XI3, Q84PB3, P39935, P39936, Q10475, Q553R3, Q5Z5Q3, Q62448, Q93ZT6, Q98TX3, O73777, P78344, P79398, Q5R7J9, Q95L46, Q8SVP8, O82233, Q8W4Q4, Q94BR1, Q9STL9, A3CEM4, Q0DBW8

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
CAMK1G	up-regulates	EIF4G3	phosphorylation
PNCK	up-regulates	EIF4G3	phosphorylation
CAMK1	unknown	EIF4G3	phosphorylation
EIF3_complex	“up-regulates activity”	EIF4G3	stabilization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 141 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
Translation initiation complex formation	12	25.7×	1e-11
Dengue Virus Genome Translation and Replication	7	24.9×	9e-07
Deadenylation of mRNA	5	24.7×	9e-05
Ribosomal scanning and start codon recognition	11	23.5×	2e-10
Formation of the ternary complex, and subsequently, the 43S complex	8	19.4×	7e-07
M-decay: degradation of maternal mRNAs by maternally stored factors	5	18.3×	3e-04
L13a-mediated translational silencing of Ceruloplasmin expression	14	15.9×	4e-11
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	5	15.3×	7e-04

GO biological processes:

GO term	Partners	Fold	FDR
formation of cytoplasmic translation initiation complex	6	54.4×	3e-07
translational initiation	13	37.6×	9e-15
regulation of translational initiation	5	18.9×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	171
Likely benign	12
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3892395	NM_001391906.1(EIF4G3):c.4801_4825dup (p.Lys1609fs)	Likely pathogenic

SpliceAI

5332 predictions. Top by Δscore:

Variant	Effect	Δscore
1:20807496:CAAAT:C	acceptor_gain	1.0000
1:20807497:AAAT:A	acceptor_gain	1.0000
1:20807498:AAT:A	acceptor_gain	1.0000
1:20807499:AT:A	acceptor_gain	1.0000
1:20807499:ATCTG:A	acceptor_loss	1.0000
1:20807500:TCTGC:T	acceptor_loss	1.0000
1:20807501:C:CC	acceptor_gain	1.0000
1:20807501:CT:C	acceptor_loss	1.0000
1:20809287:T:C	donor_gain	1.0000
1:20810736:A:AC	donor_gain	1.0000
1:20810737:C:CT	donor_gain	1.0000
1:20810737:CTGG:C	donor_gain	1.0000
1:20810885:C:CC	acceptor_gain	1.0000
1:20817536:CTT:C	acceptor_gain	1.0000
1:20817538:TC:T	acceptor_loss	1.0000
1:20817539:C:CG	acceptor_loss	1.0000
1:20825094:TCTTA:T	donor_loss	1.0000
1:20825095:CTTA:C	donor_loss	1.0000
1:20825096:TTACC:T	donor_loss	1.0000
1:20825097:TAC:T	donor_loss	1.0000
1:20825098:A:AG	donor_loss	1.0000
1:20825099:CC:C	donor_loss	1.0000
1:20825199:C:CC	acceptor_gain	1.0000
1:20827695:TTCT:T	acceptor_gain	1.0000
1:20827697:CT:C	acceptor_gain	1.0000
1:20827699:C:CC	acceptor_gain	1.0000
1:20829140:AACTT:A	donor_loss	1.0000
1:20829141:ACTTA:A	donor_loss	1.0000
1:20829142:CTT:C	donor_loss	1.0000
1:20829143:TTA:T	donor_loss	1.0000

AlphaMissense

10793 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:20807353:A:G	L1575P	1.000
1:20807355:C:A	W1574C	1.000
1:20807355:C:G	W1574C	1.000
1:20807357:A:G	W1574R	1.000
1:20807357:A:T	W1574R	1.000
1:20807364:G:C	F1571L	1.000
1:20807364:G:T	F1571L	1.000
1:20807365:A:G	F1571S	1.000
1:20807366:A:G	F1571L	1.000
1:20807383:A:G	L1565P	1.000
1:20807430:C:A	W1549C	1.000
1:20807430:C:G	W1549C	1.000
1:20807431:C:G	W1549S	1.000
1:20807432:A:G	W1549R	1.000
1:20807432:A:T	W1549R	1.000
1:20807473:A:G	L1535P	1.000
1:20810773:A:G	L1514P	1.000
1:20810782:A:G	L1511P	1.000
1:20860454:C:G	A1003P	1.000
1:20860465:A:C	I999S	1.000
1:20860465:A:G	I999T	1.000
1:20860465:A:T	I999N	1.000
1:20860468:T:G	Q998P	1.000
1:20860474:A:T	I996N	1.000
1:20860509:C:A	W984C	1.000
1:20860509:C:G	W984C	1.000
1:20860511:A:G	W984R	1.000
1:20860511:A:T	W984R	1.000
1:20862232:C:A	R980M	1.000
1:20862232:C:G	R980T	1.000

dbSNP variants (sampled 300 via entrez): RS1000008019 (1:20903367 A>G), RS1000013542 (1:21063382 A>C), RS1000040589 (1:20942337 A>G), RS1000043448 (1:20974305 G>A), RS1000046438 (1:20886479 T>C), RS1000061565 (1:21001473 A>C,G), RS1000062592 (1:21090322 A>C), RS1000065781 (1:21108497 G>A), RS1000071331 (1:21150997 T>G), RS1000075538 (1:21133722 G>A), RS1000080475 (1:20863366 C>T), RS1000083240 (1:21028880 A>T), RS1000085337 (1:21063661 T>C), RS1000092434 (1:20930619 C>T), RS1000098243 (1:21036907 T>A,C)

Disease associations

OMIM: gene MIM:603929 | disease phenotypes: MIM:612356

GenCC curated gene-disease

Mondo (3): prostate cancer (MONDO:0008315), breast ductal adenocarcinoma (MONDO:0005590), heparin cofactor 2 deficiency (MONDO:0012876)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST002663_1	Superior frontal gyrus grey matter volume	8.000000e-09
GCST002663_10	Superior frontal gyrus grey matter volume	2.000000e-06
GCST003075_82	Cognitive decline rate in late mild cognitive impairment	7.000000e-08
GCST003075_93	Cognitive decline rate in late mild cognitive impairment	4.000000e-08
GCST006665_1	Social science traits (pleiotropy) (HIPO component 1)	1.000000e-08
GCST007325_300	General risk tolerance (MTAG)	1.000000e-15
GCST007565_11	Morning person	5.000000e-19
GCST007565_185	Morning person	9.000000e-18
GCST007565_20	Morning person	1.000000e-17
GCST007565_22	Morning person	3.000000e-18
GCST007576_36	Chronotype	5.000000e-19
GCST007979_3	Postoperative acute renal failure after cardiac surgery	7.000000e-07
GCST90002379_2	Basophil count	7.000000e-20
GCST90002380_77	Basophil percentage of white cells	2.000000e-18
GCST90002381_565	Eosinophil count	2.000000e-10
GCST90002382_61	Eosinophil percentage of white cells	3.000000e-09
GCST90002397_173	Mean spheric corpuscular volume	4.000000e-15
GCST90002403_36	Red blood cell count	2.000000e-14

EFO canonical traits (14, from GWAS)

EFO ID	Trait name
EFO:0006516	superior frontal gyrus grey matter volume measurement
EFO:0007710	cognitive decline measurement
EFO:0007006	depressive symptom measurement
EFO:0007660	neuroticism measurement
EFO:0007869	wellbeing measurement
EFO:0008579	risk-taking behaviour
EFO:0008328	chronotype measurement
EFO:0009951	response to surgery
EFO:0009955	post-operative acute kidney injury
EFO:0005090	basophil count
EFO:0007992	basophil percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004305	erythrocyte count

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
C562865	Heparin Cofactor II Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	4
cobaltous chloride	decreases expression	2
Acetaminophen	decreases expression, increases expression	2
Cisplatin	decreases expression	2
Formaldehyde	increases expression	2
Valproic Acid	affects cotreatment, increases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
FR900359	affects phosphorylation	1
testosterone enanthate	affects expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
sodium arsenate	decreases expression	1
trichostatin A	decreases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
sodium bichromate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
coumarin	increases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	decreases ADP-ribosylation	1
K 7174	increases expression	1
bisphenol S	increases methylation	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	increases abundance, increases expression	1
Benzophenoneidum	increases expression	1
Cadmium	decreases expression, increases abundance	1
Carbamazepine	affects expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer