EVI5

Summary

EVI5 (ecotropic viral integration site 5, HGNC:3501) is a protein-coding gene on chromosome 1p22.1, encoding Ecotropic viral integration site 5 protein homolog (O60447). Functions as a regulator of cell cycle progression by stabilizing the FBXO5 protein and promoting cyclin-A accumulation during interphase.

Enables GTPase activator activity and small GTPase binding activity. Involved in positive regulation of GTPase activity and retrograde transport, endosome to Golgi. Located in cytosol.

Source: NCBI Gene 7813 — RefSeq curated summary.

At a glance

• GWAS associations: 30
• Clinical variants (ClinVar): 137 total
• MANE Select transcript: NM_001350197

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3501
Approved symbol	EVI5
Name	ecotropic viral integration site 5
Location	1p22.1
Locus type	gene with protein product
Status	Approved
Aliases	NB4S
Ensembl gene	ENSG00000067208
Ensembl biotype	protein_coding
OMIM	602942
Entrez	7813

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 25 protein_coding, 7 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000370331, ENST00000466778, ENST00000468580, ENST00000474806, ENST00000492513, ENST00000492613, ENST00000540033, ENST00000684568, ENST00000706843, ENST00000706845, ENST00000706846, ENST00000706847, ENST00000706867, ENST00000706868, ENST00000706869, ENST00000706870, ENST00000706883, ENST00000706884, ENST00000706885, ENST00000933837, ENST00000933838, ENST00000933839, ENST00000933840, ENST00000948805, ENST00000948806, ENST00000948807, ENST00000948808, ENST00000948809, ENST00000948810, ENST00000948811, ENST00000948812, ENST00000948813, ENST00000948814, ENST00000948815, ENST00000948816

RefSeq mRNA: 8 — MANE Select: NM_001350197 NM_001308248, NM_001350197, NM_001350198, NM_001377210, NM_001377211, NM_001377212, NM_001377213, NM_005665

CCDS: CCDS30774, CCDS76179, CCDS91002

Canonical transcript exons

ENST00000684568 — 20 exons

Exon	Start	End
ENSE00000777004	92693802	92693899
ENSE00001618885	92694299	92694388
ENSE00001643069	92736398	92736627
ENSE00001761742	92695310	92695453
ENSE00003997166	92703395	92703619
ENSE00003997185	92702141	92702215
ENSE00003997186	92697860	92697985
ENSE00003997190	92704555	92704744
ENSE00003997306	92784836	92785108
ENSE00003997368	92677158	92677218
ENSE00003997369	92624176	92624334
ENSE00003997370	92625794	92625934
ENSE00003997371	92605307	92605402
ENSE00003997372	92665939	92665992
ENSE00003997373	92662719	92662865
ENSE00003997374	92563642	92563737
ENSE00003997375	92636202	92636336
ENSE00003997376	92508696	92513970
ENSE00003997377	92663420	92663452
ENSE00003997378	92607581	92607727

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 97.09.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.7049 / max 223.1221, expressed in 1749 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
13287	9.6033	1710
13286	1.8213	1017
13289	1.1260	729
13288	0.5983	361
13290	0.5560	157

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	97.09	gold quality
tendon	UBERON:0000043	95.00	gold quality
sural nerve	UBERON:0015488	94.57	gold quality
adrenal tissue	UBERON:0018303	93.12	gold quality
tendon of biceps brachii	UBERON:0008188	92.34	gold quality
choroid plexus epithelium	UBERON:0003911	91.44	gold quality
skin of hip	UBERON:0001554	90.99	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.07	gold quality
seminal vesicle	UBERON:0000998	90.04	gold quality
parietal pleura	UBERON:0002400	90.00	gold quality
corpus callosum	UBERON:0002336	89.36	gold quality
pleura	UBERON:0000977	88.92	gold quality
visceral pleura	UBERON:0002401	88.54	gold quality
colonic epithelium	UBERON:0000397	88.36	gold quality
medial globus pallidus	UBERON:0002477	88.21	gold quality
germinal epithelium of ovary	UBERON:0001304	87.74	gold quality
placenta	UBERON:0001987	87.47	gold quality
bronchial epithelial cell	CL:0002328	87.38	gold quality
mucosa of paranasal sinus	UBERON:0005030	87.27	gold quality
stromal cell of endometrium	CL:0002255	87.04	gold quality
cranial nerve II	UBERON:0000941	86.80	gold quality
jejunal mucosa	UBERON:0000399	86.61	gold quality
palpebral conjunctiva	UBERON:0001812	85.99	gold quality
decidua	UBERON:0002450	85.95	gold quality
CA1 field of hippocampus	UBERON:0003881	85.85	gold quality
upper leg skin	UBERON:0004262	85.83	gold quality
hair follicle	UBERON:0002073	85.75	silver quality
mucosa of sigmoid colon	UBERON:0004993	85.56	gold quality
monocyte	CL:0000576	85.45	gold quality
globus pallidus	UBERON:0001875	85.43	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.07
E-MTAB-6379	no	53.32
E-GEOD-70580	no	19.35

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

243 targeting EVI5, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-186-5P	99.99	70.83	3707

Literature-anchored findings (GeneRIF, showing 13)

• a novel centrosomal protein with a complex expression pattern and subcellular localization, possibly involved in centrosome stability and dynamics (PMID:16033705)
• Data provide evidence that EVI5 is an essential component of the protein machinery facilitating the final stages of cell septation at the end of mitosis. (PMID:16764853)
• Evi5 is a Rab11 binding protein and that Evi5 may cooperate with Rab11 to coordinate vesicular trafficking, cytokinesis, and cell cycle control independent of GTPase-activating protein function (PMID:17229837)
• EVI5 is a risk gene for multiple sclerosis. (PMID:18401352)
• Stem cell exhaustion due to Runx1 deficiency is prevented by Evi5 activation in leukemogenesis. (PMID:20008790)
• An analysis and fine mapping of GFI-EVI5-RPL5-FAM69A locus, genotyping eight Tag-single nucleotide polymorphisms in 732 multiple sclerosis patients and 974 controls from Spain, was performed. (PMID:20087403)
• cellular functions exhibited by the Evi5 family members (PMID:23669355)
• in HLA-DRB1 positive patients, EVI5 was associated with attacks of greater severity and worse recovery in Multiple sclerosis . (PMID:24130709)
• Data show that heat shock transcription factor 1/miR-135b/reversion-inducing-cysteine-rich protein with kazal motifs and ecotropic viral integration site 5 axis provides novel insight into the mechanisms of hepatocellular carcinoma metastasis. (PMID:25537516)
• EVI5 as a strong candidate disease risk gene in the 1p22.1 multiple sclerosis risk locus (PMID:26433934)
• EVI5 is an useful independent prognostic marker of survival and recurrence in hepatocellular carcinoma (PMID:28765910)
• The allele and genotype frequencies of rs6680578 and rs11810217 were not significantly different between relapsing-remitting multiple sclerosis (MS) cases and controls. However, in the rs10735781 the GG genotype was significantly associated with MS risk in recessive and co-dominant models. T G T haplotype (rs6680578, rs10735781 and rs11810217 respectively) was associated with MS risk. (PMID:29141798)
• EVI5 is an oncogene that regulates the proliferation and metastasis of NSCLC cells. (PMID:32393392)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	evi5b	ENSDARG00000070839
mus_musculus	Evi5	ENSMUSG00000011831
rattus_norvegicus	Evi5	ENSRNOG00000002039

Paralogs (45): RABGAP1 (ENSG00000011454), TBC1D22A (ENSG00000054611), TBC1D22B (ENSG00000065491), TBC1D1 (ENSG00000065882), TBC1D25 (ENSG00000068354), TBC1D2 (ENSG00000095383), TBC1D10A (ENSG00000099992), SGSM3 (ENSG00000100359), TBC1D17 (ENSG00000104946), TBC1D13 (ENSG00000107021), TBC1D12 (ENSG00000108239), TBC1D9 (ENSG00000109436), TBC1D30 (ENSG00000111490), TBC1D15 (ENSG00000121749), TBC1D5 (ENSG00000131374), TBC1D14 (ENSG00000132405), TBC1D8B (ENSG00000133138), TBC1D4 (ENSG00000136111), GRTP1 (ENSG00000139835), SGSM2 (ENSG00000141258), EVI5L (ENSG00000142459), TBCK (ENSG00000145348), USP6NL (ENSG00000148429), RABGAP1L (ENSG00000152061), SGSM1 (ENSG00000167037), TBC1D21 (ENSG00000167139), TBC1D2B (ENSG00000167202), TBC1D16 (ENSG00000167291), TBC1D10B (ENSG00000169221), TBC1D10C (ENSG00000175463), TBC1D28 (ENSG00000189375), TBC1D9B (ENSG00000197226), TBC1D8 (ENSG00000204634), TBC1D26 (ENSG00000214946), TBC1D3G (ENSG00000260287), TBC1D3K (ENSG00000273513), TBC1D3H (ENSG00000274226), TBC1D3D (ENSG00000274419), TBC1D3L (ENSG00000274512), TBC1D3 (ENSG00000274611)

Protein

Protein identifiers

Ecotropic viral integration site 5 protein homolog — O60447 (reviewed: O60447)

Alternative names: Neuroblastoma stage 4S gene protein

All UniProt accessions (9): O60447, A0A804HIC4, A0A9L9PXD7, A0A9L9PXE3, A0A9L9PXL1, A0A9L9PXL6, A0A9L9PXM6, A0A9L9PYE8, A0A9L9PYF1

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a regulator of cell cycle progression by stabilizing the FBXO5 protein and promoting cyclin-A accumulation during interphase. May play a role in cytokinesis.

Subunit / interactions. Dimeric and monomeric. Interacts with alpha- and gamma-tubulin. Interacts with FBXO5. Interacts with the chromosome passenger complex (CPC) which is at least composed of AURKB/aurora-B, BIRC5/survivin, CDCA8/borealin and INCENP.

Subcellular location. Nucleus. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Spindle.

Tissue specificity. Expressed in various cell lines (at protein level). Expressed in a wide range of tissues including brain and adrenal.

Post-translational modifications. Probably phosphorylated by PLK1; may be required for degradation during mitosis. Ubiquitinated. Degradation during prophase is ubiquitin-dependent.

Disease relevance. A chromosomal aberration involving EVI5 is found is a patient with stage 4S neuroblastoma. Translocation t(1;10)(p22;q21) that forms a EVI5-TRNG10 fusion protein. TRNG10 is a probable structural transcript which is normally not translated.

Induction. Down-regulated during mitosis through proteasomal degradation.

Miscellaneous. Depletion of EVI5 by RNAi causes cell cycle arrest and mitotic abnormalities.

Isoforms (2)

UniProt ID	Names	Canonical?
O60447-1	1	yes
O60447-2	2

RefSeq proteins (8): NP_001295177, NP_001337126, NP_001337127, NP_001364139, NP_001364140, NP_001364141, NP_001364142, NP_005656 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000195	Rab-GAP-TBC_dom	Domain
IPR035969	Rab-GAP_TBC_sf	Homologous_superfamily
IPR050302	Rab_GAP_TBC_domain	Family

Pfam: PF00566

UniProt features (27 total): region of interest 7, modified residue 6, compositionally biased region 3, sequence variant 3, sequence conflict 3, chain 1, domain 1, site 1, splice variant 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60447-F1	75.22	0.43

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 (1): 594 (breakpoint for translocation to form evi5-trng10 fusion protein)

Post-translational modifications (6): 102, 113, 497, 689, 776, 778

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 274 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, SCHWAB_TARGETS_OF_BMYB_POLYMORPHIC_VARIANTS_DN, AAGCCAT_MIR135A_MIR135B, GOBP_REGULATION_OF_GTPASE_ACTIVITY, GOBP_VESICLE_MEDIATED_TRANSPORT, GOMF_GTPASE_BINDING, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOCC_MICROTUBULE_ORGANIZING_CENTER, GTGCCTT_MIR506, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, GOBP_REGULATION_OF_HYDROLASE_ACTIVITY, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_CILIUM_ORGANIZATION

GO Biological Process (3): retrograde transport, endosome to Golgi (GO:0042147), positive regulation of GTPase activity (GO:0043547), cell division (GO:0051301)

GO Molecular Function (3): GTPase activator activity (GO:0005096), small GTPase binding (GO:0031267), protein binding (GO:0005515)

GO Cellular Component (6): nucleus (GO:0005634), centrosome (GO:0005813), spindle (GO:0005819), cytosol (GO:0005829), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
GTPase activity	2
intracellular membraneless organelle	2
cellular anatomical structure	2
intercellular transport	1
endosomal transport	1
cytosolic transport	1
regulation of GTPase activity	1
positive regulation of hydrolase activity	1
cellular process	1
enzyme activator activity	1
GTPase regulator activity	1
GTPase binding	1
binding	1
intracellular membrane-bounded organelle	1
centriole	1
microtubule organizing center	1
microtubule cytoskeleton	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

880 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EVI5	FBXO5	Q9UKT4	863
EVI5	RAB11A	P24410	826
EVI5	ODF2	Q5BJF6	793
EVI5	HLA-DRB1	P01911	694
EVI5	NBPF1	Q3BBV0	657
EVI5	GMNN	O75496	649
EVI5	PLK1	P53350	631
EVI5	CNTRL	Q7Z7A1	631
EVI5	RPL5	P46777	619
EVI5	FBXO43	Q4G163	594
EVI5	BTRC	Q9Y297	536
EVI5	CLEC16A	Q2KHT3	526
EVI5	RAB35	Q15286	525
EVI5	DIPK1A	Q5T7M9	518
EVI5	GFI1	Q99684	516
EVI5	CDC16	Q13042	516

IntAct

221 interactions, top by confidence:

A	B	Type	Score
RAB11A	EVI5	psi-mi:“MI:0914”(association)	0.800
EVI5	RAB11A	psi-mi:“MI:0915”(physical association)	0.800
EVI5	RAB11A	psi-mi:“MI:0407”(direct interaction)	0.800
PSMD2	PSMD11	psi-mi:“MI:0914”(association)	0.730
EVI5	MB21D2	psi-mi:“MI:0915”(physical association)	0.670
EVI5	REP15	psi-mi:“MI:0915”(physical association)	0.670
PLK1	EVI5	psi-mi:“MI:0914”(association)	0.660
DLG1	EVI5	psi-mi:“MI:0407”(direct interaction)	0.620
EVI5	DLG1	psi-mi:“MI:0407”(direct interaction)	0.620
DLG3	EVI5	psi-mi:“MI:0407”(direct interaction)	0.590
EVI5	DLG3	psi-mi:“MI:0407”(direct interaction)	0.590
EVI5	MCRS1	psi-mi:“MI:0915”(physical association)	0.560
EVI5	FAM161A	psi-mi:“MI:0915”(physical association)	0.560
EVI5	ELOA	psi-mi:“MI:0915”(physical association)	0.560
EVI5	TNFAIP8L1	psi-mi:“MI:0915”(physical association)	0.560
EVI5	ZNF446	psi-mi:“MI:0915”(physical association)	0.560
EVI5	LENG1	psi-mi:“MI:0915”(physical association)	0.560
EVI5	TCEANC	psi-mi:“MI:0915”(physical association)	0.560
EVI5	MORF4L2	psi-mi:“MI:0915”(physical association)	0.560
EVI5	PRPF31	psi-mi:“MI:0915”(physical association)	0.560
EVI5	CSNK1D	psi-mi:“MI:0915”(physical association)	0.560
EVI5	IMP3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (77): EVI5 (Affinity Capture-MS), EVI5 (Affinity Capture-MS), EVI5 (Affinity Capture-MS), EVI5 (Affinity Capture-MS), EVI5 (Affinity Capture-MS), EVI5 (Affinity Capture-MS), EVI5 (Affinity Capture-MS), STX3 (Affinity Capture-Western), MYO5B (Affinity Capture-Western), SYTL4 (Affinity Capture-Western), EVI5 (Reconstituted Complex), EVI5 (Affinity Capture-MS), EVI5 (Affinity Capture-MS), EVI5 (Synthetic Lethality), EVI5 (Affinity Capture-MS)

ESM2 similar proteins: A1A5B6, A6H7I8, A7E300, B9VTT2, F1LXF1, M0R7T9, O08873, O14795, O60347, O60447, P0C6S7, P11274, P22681, P22682, P49797, Q0IHY4, Q0VGY8, Q14432, Q3MII6, Q4KUS2, Q5CD77, Q62769, Q69ZT9, Q6A039, Q6F6B3, Q6P9S0, Q6PAJ1, Q6PCS4, Q6ZM89, Q765P7, Q80U28, Q80YA9, Q8BIZ1, Q8CGA2, Q8K214, Q8R1S4, Q8WXG6, Q8WXI2, Q923Q2, Q92625

Diamond homologs: A0A087WVF3, A0A087WXS9, A0A087X179, A0A087X1G2, A2AWA9, A3KGB4, A6H6A9, A6NDS4, A6NER0, A6QP29, B0R0W9, B7ZAP0, B9A6J9, H2KZZ6, O60343, O60447, O95759, O97790, P0C7X1, P35125, P58802, P97366, Q0IIM8, Q10496, Q12317, Q12344, Q28CB1, Q3UYK3, Q4KMP7, Q5R372, Q5RAN1, Q5RCW6, Q5SVR0, Q5TC63, Q5ZJ17, Q60949, Q66K14, Q6DHY5, Q6IPX1, Q6ZT07

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
EVI5	down-regulates	PLK1

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 135 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
Ras activation upon Ca2+ influx through NMDA receptor	5	35.2×	2e-05
Unblocking of NMDA receptors, glutamate binding and activation	5	33.6×	2e-05
Negative regulation of NMDA receptor-mediated neuronal transmission	5	33.6×	2e-05
Long-term potentiation	5	29.4×	3e-05
Assembly and cell surface presentation of NMDA receptors	9	28.2×	4e-09
Neurexins and neuroligins	10	24.3×	3e-09
Protein-protein interactions at synapses	6	19.7×	3e-05

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	9	44.7×	2e-10
protein localization to synapse	6	39.3×	1e-06
receptor clustering	7	37.3×	2e-07
regulation of postsynaptic membrane neurotransmitter receptor levels	6	25.4×	1e-05
cell-cell adhesion	10	8.7×	2e-05
protein-containing complex assembly	8	7.8×	6e-04
exocytosis	6	7.8×	5e-03
protein localization to plasma membrane	7	6.5×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	110
Likely benign	4
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

4928 predictions. Top by Δscore:

Variant	Effect	Δscore
1:92563637:CTTA:C	donor_loss	1.0000
1:92563638:TTACC:T	donor_loss	1.0000
1:92563639:TACCT:T	donor_loss	1.0000
1:92563640:A:AC	donor_gain	1.0000
1:92563640:AC:A	donor_gain	1.0000
1:92563640:ACCT:A	donor_gain	1.0000
1:92563640:ACCTC:A	donor_loss	1.0000
1:92563641:C:CA	donor_loss	1.0000
1:92563641:C:CC	donor_gain	1.0000
1:92563641:CC:C	donor_gain	1.0000
1:92563641:CCT:C	donor_gain	1.0000
1:92563641:CCTC:C	donor_gain	1.0000
1:92563734:CTTT:C	acceptor_gain	1.0000
1:92563735:TTTC:T	acceptor_loss	1.0000
1:92563736:TT:T	acceptor_gain	1.0000
1:92563736:TTCTG:T	acceptor_loss	1.0000
1:92563737:TC:T	acceptor_loss	1.0000
1:92563738:C:CC	acceptor_gain	1.0000
1:92563743:T:C	acceptor_gain	1.0000
1:92563743:T:TC	acceptor_gain	1.0000
1:92563745:G:C	acceptor_gain	1.0000
1:92563745:G:GC	acceptor_gain	1.0000
1:92563749:C:CT	acceptor_gain	1.0000
1:92563750:A:T	acceptor_gain	1.0000
1:92563754:C:CT	acceptor_gain	1.0000
1:92563755:A:T	acceptor_gain	1.0000
1:92563757:C:CT	acceptor_gain	1.0000
1:92605422:C:CT	acceptor_gain	1.0000
1:92607576:TTTAC:T	donor_loss	1.0000
1:92607577:TTA:T	donor_loss	1.0000

AlphaMissense

5499 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:92665985:C:G	R433P	1.000
1:92677205:A:C	Y415D	1.000
1:92695377:A:G	L325P	1.000
1:92695384:A:G	W323R	1.000
1:92695384:A:T	W323R	1.000
1:92697905:C:A	M284I	1.000
1:92697905:C:G	M284I	1.000
1:92697905:C:T	M284I	1.000
1:92697906:A:G	M284T	1.000
1:92697914:T:A	K281N	1.000
1:92697914:T:G	K281N	1.000
1:92697917:A:C	F280L	1.000
1:92697917:A:T	F280L	1.000
1:92697919:A:G	F280L	1.000
1:92697928:G:T	R277S	1.000
1:92697930:A:G	L276P	1.000
1:92697965:G:C	F264L	1.000
1:92697965:G:T	F264L	1.000
1:92697967:A:G	F264L	1.000
1:92697970:C:G	A263P	1.000
1:92702148:A:G	L255P	1.000
1:92702157:C:T	G252E	1.000
1:92702158:C:G	G252R	1.000
1:92702158:C:T	G252R	1.000
1:92702165:A:C	F249L	1.000
1:92702165:A:T	F249L	1.000
1:92702167:A:G	F249L	1.000
1:92702169:G:T	A248D	1.000
1:92702171:A:C	S247R	1.000
1:92702171:A:T	S247R	1.000

dbSNP variants (sampled 300 via entrez): RS1000016019 (1:92683427 A>G), RS1000018904 (1:92557217 T>C), RS1000048372 (1:92728190 T>A), RS1000050757 (1:92601205 C>T), RS1000052534 (1:92686051 G>A), RS1000055329 (1:92768092 A>G), RS1000067703 (1:92779279 T>A,C), RS1000068245 (1:92678361 T>C), RS1000071983 (1:92516914 G>A), RS1000077705 (1:92606567 TTC>T), RS1000080569 (1:92728459 C>T), RS1000092591 (1:92645967 G>A,C), RS1000095050 (1:92644240 C>T), RS1000112067 (1:92636973 A>C), RS1000115943 (1:92755328 T>C)

Disease associations

OMIM: gene MIM:602942 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

30 associations (top):

Study	Trait	p-value
GCST000425_2	Multiple sclerosis	3.000000e-06
GCST000760_20	Cholesterol, total	3.000000e-08
GCST001198_19	Multiple sclerosis	6.000000e-15
GCST002221_46	Cholesterol, total	2.000000e-08
GCST002896_4	Cholesterol, total	1.000000e-09
GCST002898_3	LDL cholesterol	2.000000e-08
GCST003340_1	Epstein Barr virus nuclear antigen 1 IgG levels or multiple sclerosis	2.000000e-08
GCST003566_7	Multiple sclerosis	4.000000e-10
GCST004235_73	Total cholesterol levels	3.000000e-14
GCST004609_179	Monocyte percentage of white cells	7.000000e-11
GCST004625_8	Monocyte count	2.000000e-44
GCST005531_25	Multiple sclerosis	1.000000e-26
GCST005752_181	Systemic lupus erythematosus	1.000000e-07
GCST006612_121	LDL cholesterol	5.000000e-17
GCST006614_71	Total cholesterol levels	2.000000e-12
GCST007400_6	Systemic lupus erythematosus	5.000000e-07
GCST007563_13	Allergic disease (asthma, hay fever or eczema)	7.000000e-09
GCST007564_2	Asthma or allergic disease (pleiotropy)	4.000000e-08
GCST009597_247	Multiple sclerosis	3.000000e-30
GCST010204_192	Low density lipoprotein cholesterol levels	2.000000e-12
GCST010243_83	Apolipoprotein B levels	1.000000e-10
GCST010245_178	LDL cholesterol levels	2.000000e-14
GCST011343_1	Body fat percentage and LDL-C (pairwise)	5.000000e-15
GCST011346_4	Total cholesterol levels	2.000000e-09
GCST011347_5	Low density lipoprotein cholesterol levels	2.000000e-08
GCST90002392_272	Mean corpuscular volume	2.000000e-13
GCST90002393_39	Monocyte count	3.000000e-16
GCST90002394_145	Monocyte percentage of white cells	1.000000e-18
GCST90002394_146	Monocyte percentage of white cells	3.000000e-14
GCST90002397_637	Mean spheric corpuscular volume	7.000000e-16

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004574	total cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0007790	Epstein Barr virus nuclear antigen 1 IgG measurement
EFO:0007989	monocyte percentage of leukocytes
EFO:0005091	monocyte count
EFO:0004615	apolipoprotein B measurement
EFO:0007800	body fat percentage

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	4
trichostatin A	affects expression, decreases expression	3
sodium arsenite	decreases expression, increases expression	2
perfluorooctane sulfonic acid	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
geldanamycin	increases expression	1
triphenyl phosphate	affects expression	1
uranyl acetate	affects expression	1
bisphenol A	decreases methylation	1
cupric oxide	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
K 7174	increases expression	1
abrine	decreases expression	1
bisphenol S	decreases methylation	1
jinfukang	decreases expression	1
(+)-JQ1 compound	increases expression	1
MT19c compound	increases expression	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
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	increases expression	1
Vorinostat	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	affects methylation	1
Calcitriol	increases expression	1
Cisplatin	decreases expression	1
Coumestrol	decreases expression	1
Colforsin	increases expression	1

Clinical trials (associated diseases)

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