INTS8

Summary

INTS8 (integrator complex subunit 8, HGNC:26048) is a protein-coding gene on chromosome 8q22.1, encoding Integrator complex subunit 8 (Q75QN2). Component of the integrator complex, a multiprotein complex that terminates RNA polymerase II (Pol II) transcription in the promoter-proximal region of genes. It is a common-essential gene (DepMap: required in 97.2% of cancer cell lines).

This gene encodes a subunit of the Integrator complex which is involved in the cleavage of small nuclear RNAs U1 and U2 within the nucleus. The encoded protein associates with RNA polymerase II and is recruited to the U1 and U2 small nuclear RNA genes. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 55656 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder with cerebellar hypoplasia and spasticity (Limited, GenCC)
• GWAS associations: 7
• Clinical variants (ClinVar): 178 total — 2 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 14
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 97.2% of screened cell lines (common-essential)
• MANE Select transcript: NM_017864

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26048
Approved symbol	INTS8
Name	integrator complex subunit 8
Location	8q22.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20530, INT8, MGC131633
Ensembl gene	ENSG00000164941
Ensembl biotype	protein_coding
OMIM	611351
Entrez	55656

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 8 protein_coding, 7 retained_intron, 4 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000343161, ENST00000517918, ENST00000519053, ENST00000519457, ENST00000519736, ENST00000520315, ENST00000520526, ENST00000520845, ENST00000520853, ENST00000521155, ENST00000521860, ENST00000522171, ENST00000522261, ENST00000523206, ENST00000523321, ENST00000523352, ENST00000523731, ENST00000523808, ENST00000523998, ENST00000524333, ENST00000715987

RefSeq mRNA: 1 — MANE Select: NM_017864 NM_017864

CCDS: CCDS34925

Canonical transcript exons

ENST00000523731 — 27 exons

Exon	Start	End
ENSE00002107450	94880118	94881746
ENSE00003465655	94866158	94866191
ENSE00003471137	94838463	94838618
ENSE00003496430	94849916	94850091
ENSE00003505646	94853805	94853915
ENSE00003507657	94828975	94829026
ENSE00003522272	94876221	94876285
ENSE00003523780	94865506	94865690
ENSE00003531728	94849462	94849532
ENSE00003537927	94827722	94827793
ENSE00003541345	94867276	94867337
ENSE00003549778	94851553	94851686
ENSE00003552282	94842347	94842488
ENSE00003571507	94874552	94874602
ENSE00003588075	94831992	94832174
ENSE00003594273	94876446	94876489
ENSE00003606618	94873374	94873477
ENSE00003607102	94867140	94867196
ENSE00003611286	94859511	94859632
ENSE00003631923	94871884	94872002
ENSE00003634698	94836524	94836631
ENSE00003638390	94876074	94876147
ENSE00003650845	94841491	94841591
ENSE00003659015	94827263	94827403
ENSE00003659709	94824893	94825067
ENSE00003677284	94856777	94856978
ENSE00003889801	94823287	94823561

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 99.62.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.2071 / max 249.6083, expressed in 1813 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
89801	22.7981	1809
89802	1.0044	602
89800	0.4045	190

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.62	gold quality
oocyte	CL:0000023	99.03	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	97.80	gold quality
calcaneal tendon	UBERON:0003701	96.60	gold quality
ventricular zone	UBERON:0003053	96.09	gold quality
colonic epithelium	UBERON:0000397	95.72	gold quality
body of pancreas	UBERON:0001150	95.32	gold quality
endocervix	UBERON:0000458	94.94	gold quality
ganglionic eminence	UBERON:0004023	94.68	gold quality
body of uterus	UBERON:0009853	94.42	gold quality
right ovary	UBERON:0002118	94.27	gold quality
rectum	UBERON:0001052	94.09	gold quality
left ovary	UBERON:0002119	93.89	gold quality
right lobe of thyroid gland	UBERON:0001119	93.87	gold quality
bone marrow cell	CL:0002092	93.58	gold quality
choroid plexus epithelium	UBERON:0003911	93.51	gold quality
granulocyte	CL:0000094	93.49	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.46	gold quality
ovary	UBERON:0000992	93.43	gold quality
ectocervix	UBERON:0012249	93.33	gold quality
mucosa of transverse colon	UBERON:0004991	93.27	gold quality
leukocyte	CL:0000738	93.26	gold quality
monocyte	CL:0000576	93.25	gold quality
right uterine tube	UBERON:0001302	93.25	gold quality
pylorus	UBERON:0001166	93.22	gold quality
pancreas	UBERON:0001264	93.22	gold quality
mononuclear cell	CL:0000842	93.18	gold quality
cerebellar hemisphere	UBERON:0002245	93.17	gold quality
cerebellar cortex	UBERON:0002129	93.10	gold quality
embryo	UBERON:0000922	93.09	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.67

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

30 targeting INTS8, 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-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-3924	100.00	72.09	2394
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-1284	99.67	73.56	1353
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-3177-5P	99.65	70.38	1174
HSA-MIR-7844-5P	99.55	68.56	1428
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-361-5P	98.95	70.16	1340
HSA-MIR-374A-3P	98.87	67.82	1531
HSA-MIR-222-5P	98.75	69.17	1242
HSA-MIR-16-1-3P	98.70	69.23	1538
HSA-MIR-6867-3P	98.12	66.07	1305
HSA-MIR-3129-3P	97.85	67.63	1246
HSA-MIR-5583-5P	97.85	67.61	1243
HSA-MIR-449C-3P	97.75	67.86	462
HSA-MIR-4287	97.55	67.24	1247
HSA-MIR-4685-3P	97.55	67.35	1255

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 97.2% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 3)

• Mutations INTS8 cause a severe neurodevelopmental syndrome. INTS8 mutations lead in vitro to instability of the complex and impaired function. (PMID:28542170)
• Integrator Recruits Protein Phosphatase 2A to Prevent Pause Release and Facilitate Transcription Termination. (PMID:32966759)
• INTS8 is a therapeutic target for intrahepatic cholangiocarcinoma via the integration of bioinformatics analysis and experimental validation. (PMID:34880328)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ints8	ENSDARG00000057986
mus_musculus	Ints8	ENSMUSG00000040738
rattus_norvegicus	Ints8	ENSRNOG00000008124
drosophila_melanogaster	IntS8	FBGN0289323
caenorhabditis_elegans	ints-8	WBGENE00013021

Protein

Protein identifiers

Integrator complex subunit 8 — Q75QN2 (reviewed: Q75QN2)

Alternative names: Protein kaonashi-1

All UniProt accessions (10): E5RG48, E5RH10, E5RIN8, E5RJF0, E5RJL5, Q75QN2, H0YBQ1, H0YBS1, H0YC12, J3KNV5

UniProt curated annotations — full annotation on UniProt →

Function. Component of the integrator complex, a multiprotein complex that terminates RNA polymerase II (Pol II) transcription in the promoter-proximal region of genes. The integrator complex provides a quality checkpoint during transcription elongation by driving premature transcription termination of transcripts that are unfavorably configured for transcriptional elongation: the complex terminates transcription by (1) catalyzing dephosphorylation of the C-terminal domain (CTD) of Pol II subunit POLR2A/RPB1 and SUPT5H/SPT5, (2) degrading the exiting nascent RNA transcript via endonuclease activity and (3) promoting the release of Pol II from bound DNA. The integrator complex is also involved in terminating the synthesis of non-coding Pol II transcripts, such as enhancer RNAs (eRNAs), small nuclear RNAs (snRNAs), telomerase RNAs and long non-coding RNAs (lncRNAs). Within the integrator complex, INTS8 is required for the recruitment of protein phosphatase 2A (PP2A) to transcription pause-release checkpoint.

Subunit / interactions. Component of the Integrator complex, composed of core subunits INTS1, INTS2, INTS3, INTS4, INTS5, INTS6, INTS7, INTS8, INTS9/RC74, INTS10, INTS11/CPSF3L, INTS12, INTS13, INTS14 and INTS15. The core complex associates with protein phosphatase 2A subunits PPP2CA and PPP2R1A, to form the Integrator-PP2A (INTAC) complex.

Subcellular location. Nucleus. Chromosome.

Disease relevance. Neurodevelopmental disorder with cerebellar hypoplasia and spasticity (NEDCHS) [MIM:618572] An autosomal recessive neurodevelopmental disorder characterized by global developmental delay, profound intellectual disability, seizures, absent speech, spasticity, facial and limb dysmorphism, and subtle structural brain abnormalities including cerebellar hypoplasia. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The WFEF motif is required for the recruitment of protein phosphatase 2A (PP2A) to transcription pause-release checkpoint.

Similarity. Belongs to the Integrator subunit 8 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q75QN2-1	1	yes
Q75QN2-2	2

RefSeq proteins (1): NP_060334* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR038751	INTS8	Family
IPR057980	TPR_INTS8_C	Domain

Pfam: PF25756

UniProt features (90 total): helix 54, turn 12, strand 11, repeat 4, sequence conflict 2, sequence variant 2, chain 1, mutagenesis site 1, short sequence motif 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
8RC4	ELECTRON MICROSCOPY	3.1
9EP4	ELECTRON MICROSCOPY	3.2
7CUN	ELECTRON MICROSCOPY	3.5
7PKS	ELECTRON MICROSCOPY	3.6
8RBZ	ELECTRON MICROSCOPY	3.7
8RBX	ELECTRON MICROSCOPY	4.1
8YJB	ELECTRON MICROSCOPY	4.1
7YCX	ELECTRON MICROSCOPY	4.18
9VD9	ELECTRON MICROSCOPY	4.6
9EOF	ELECTRON MICROSCOPY	7.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q75QN2-F1	84.47	0.49

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 (1): 18

Mutagenesis-validated functional residues (1):

Position	Phenotype
24–27	abolished recruitment of protein phosphatase 2a subunits.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6807505	RNA polymerase II transcribes snRNA genes
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)

MSigDB gene sets: 185 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, GNF2_BNIP2, PAL_PRMT5_TARGETS_UP, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, PATIL_LIVER_CANCER, GOBP_RNA_SURVEILLANCE, MODULE_205, ONKEN_UVEAL_MELANOMA_UP, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, GOBP_PROTEIN_LOCALIZATION_TO_CHROMATIN, GOBP_PROTEIN_LOCALIZATION_TO_CHROMOSOME, LIAO_METASTASIS, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION

GO Biological Process (5): snRNA processing (GO:0016180), regulation of transcription elongation by RNA polymerase II (GO:0034243), snRNA 3’-end processing (GO:0034472), protein localization to chromatin (GO:0071168), RNA polymerase II transcription initiation surveillance (GO:0160240)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (6): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), integrator complex (GO:0032039), INTAC complex (GO:0160232), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
RNA Polymerase II Transcription	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
nuclear protein-containing complex	2
RNA processing	1
snRNA metabolic process	1
transcription elongation by RNA polymerase II	1
regulation of DNA-templated transcription elongation	1
snRNA processing	1
RNA 3’-end processing	1
protein localization to chromosome	1
transcription initiation at RNA polymerase II promoter	1
nuclear RNA surveillance	1
binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
integrator complex	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1660 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
INTS8	INTS11	Q5TA45	950
INTS8	INTS7	Q9NVH2	947
INTS8	INTS5	Q6P9B9	938
INTS8	INTS9	Q9NV88	884
INTS8	INTS10	Q9NVR2	828
INTS8	INTS2	Q9H0H0	799
INTS8	INTS4	Q96HW7	780
INTS8	INTS1	Q8N201	775
INTS8	INTS12	Q96CB8	755
INTS8	INTS13	Q9NVM9	722
INTS8	POLR2A	P24928	588
INTS8	INTS3	Q68E01	587
INTS8	INTS14	Q96SY0	571
INTS8	INTS6	Q9UL03	552
INTS8	POLR2B	P30876	547

IntAct

64 interactions, top by confidence:

A	B	Type	Score
PPP2R1A	STRN	psi-mi:“MI:0914”(association)	0.880
INTS5	INTS8	psi-mi:“MI:0915”(physical association)	0.700
INTS5	INTS8	psi-mi:“MI:0407”(direct interaction)	0.700
PPP2R1A	PPFIA3	psi-mi:“MI:0914”(association)	0.670
POLR2I	SUPT5H	psi-mi:“MI:0914”(association)	0.530
POLR2J	SUPT5H	psi-mi:“MI:0914”(association)	0.530
SUPT5H	POLR2D	psi-mi:“MI:0914”(association)	0.530
LAMP3	METTL15	psi-mi:“MI:0914”(association)	0.530
HAX1	CHEK1	psi-mi:“MI:0914”(association)	0.530
OPALIN	BTAF1	psi-mi:“MI:0914”(association)	0.530
PPP2CA	SMCO3	psi-mi:“MI:0914”(association)	0.420
INTS8	UBE2Z	psi-mi:“MI:0915”(physical association)	0.370
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
	BTAF1	psi-mi:“MI:0914”(association)	0.350
INTS14	SUPT5H	psi-mi:“MI:0914”(association)	0.350
POLR2B	PALM3	psi-mi:“MI:0914”(association)	0.350
POLR2E	BDP1	psi-mi:“MI:0914”(association)	0.350
POLR2F	BDP1	psi-mi:“MI:0914”(association)	0.350
POLR2K	BDP1	psi-mi:“MI:0914”(association)	0.350
PPP2CA	SUPT5H	psi-mi:“MI:0914”(association)	0.350
SEM1	PSMD1	psi-mi:“MI:0914”(association)	0.350
SSRP1	DDX39A	psi-mi:“MI:0914”(association)	0.350
TOP1	DDX39A	psi-mi:“MI:0914”(association)	0.350
POLR1F	POLR2E	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CRELD1	TMEM223	psi-mi:“MI:0914”(association)	0.350

BioGRID (75): INTS8 (Co-fractionation), INTS8 (Affinity Capture-MS), INTS8 (Affinity Capture-MS), INTS8 (Affinity Capture-MS), INTS8 (Affinity Capture-MS), INTS8 (Affinity Capture-MS), INTS8 (Affinity Capture-RNA), INTS8 (Affinity Capture-MS), INTS8 (Affinity Capture-MS), INTS8 (Affinity Capture-MS), INTS8 (Affinity Capture-MS), INTS8 (Affinity Capture-MS), INTS8 (Affinity Capture-MS), INTS8 (Affinity Capture-MS), INTS8 (Affinity Capture-MS)

ESM2 similar proteins: A1Z8X3, A1ZAK1, A5WUT8, A6NKT7, B0V0U5, C5J7W8, E9Q3L2, H2QII6, O08662, O14715, P0DJD0, P0DJD1, P42173, P42286, P42356, P49792, Q08754, Q0IEK6, Q16HH9, Q18892, Q20937, Q24118, Q4V847, Q5EB59, Q5RIW8, Q5ZKU4, Q61WP7, Q6P423, Q70PP2, Q75QN2, Q7Z3J3, Q80UK8, Q80V86, Q80YQ2, Q8BGA7, Q96N11, Q99666, Q9BVR0, Q9DE14, Q9ERU9

Diamond homologs: Q4V847, Q75QN2, Q80V86

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
INTS8	“form complex”	“Integrator complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 81 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
FGFR2 mutant receptor activation	7	106.6×	7e-12
Signaling by FGFR2 IIIa TM	7	84.2×	3e-11
Abortive elongation of HIV-1 transcript in the absence of Tat	8	79.4×	3e-12
Pausing and recovery of Tat-mediated HIV elongation	9	66.3×	9e-13
Tat-mediated HIV elongation arrest and recovery	9	66.3×	9e-13
RNA Pol II CTD phosphorylation and interaction with CE during HIV infection	8	65.3×	8e-12
Signaling by FGFR2	8	65.3×	8e-12
RNA Pol II CTD phosphorylation and interaction with CE	8	65.3×	8e-12

GO biological processes:

GO term	Partners	Fold	FDR
RNA polymerase II transcription initiation surveillance	5	59.9×	7e-06
transcription by RNA polymerase II	7	6.7×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	99
Likely benign	13
Benign	8

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
689526	NM_017864.4(INTS8):c.893A>G (p.Asp298Gly)	Pathogenic
689527	NM_017864.4(INTS8):c.2917_2925del (p.Glu973_Leu975del)	Pathogenic
2442176	NM_017864.4(INTS8):c.1075C>T (p.Arg359Ter)	Likely pathogenic

SpliceAI

4041 predictions. Top by Δscore:

Variant	Effect	Δscore
8:94827786:T:G	donor_gain	1.0000
8:94827790:GTGT:G	donor_gain	1.0000
8:94828958:A:AG	acceptor_gain	1.0000
8:94828958:AATT:A	acceptor_gain	1.0000
8:94828970:TTTA:T	acceptor_loss	1.0000
8:94828972:TA:T	acceptor_loss	1.0000
8:94828973:A:AG	acceptor_gain	1.0000
8:94828973:AGTAT:A	acceptor_gain	1.0000
8:94828974:G:GT	acceptor_gain	1.0000
8:94828974:GT:G	acceptor_gain	1.0000
8:94828974:GTA:G	acceptor_gain	1.0000
8:94828974:GTAT:G	acceptor_gain	1.0000
8:94828974:GTATG:G	acceptor_gain	1.0000
8:94829022:AAGTG:A	donor_gain	1.0000
8:94829024:GTG:G	donor_gain	1.0000
8:94829027:G:GG	donor_gain	1.0000
8:94829027:G:T	donor_loss	1.0000
8:94829028:T:G	donor_loss	1.0000
8:94829029:AA:A	donor_loss	1.0000
8:94831978:ATT:A	acceptor_gain	1.0000
8:94831980:T:A	acceptor_gain	1.0000
8:94831987:TGTA:T	acceptor_loss	1.0000
8:94831988:GTA:G	acceptor_loss	1.0000
8:94831990:A:AG	acceptor_gain	1.0000
8:94831991:G:GA	acceptor_gain	1.0000
8:94831991:GCTC:G	acceptor_gain	1.0000
8:94832020:T:TA	acceptor_gain	1.0000
8:94832169:TGCC:T	donor_gain	1.0000
8:94832171:CCAG:C	donor_gain	1.0000
8:94832172:CAG:C	donor_loss	1.0000

AlphaMissense

6543 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:94825042:T:A	W94R	1.000
8:94825042:T:C	W94R	1.000
8:94827402:T:A	W149R	1.000
8:94827402:T:C	W149R	1.000
8:94851592:T:C	L516P	1.000
8:94853805:T:A	W548R	1.000
8:94853805:T:C	W548R	1.000
8:94867318:T:A	W799R	1.000
8:94867318:T:C	W799R	1.000
8:94876255:T:A	W933R	1.000
8:94876255:T:C	W933R	1.000
8:94823501:T:A	W24R	0.999
8:94823501:T:C	W24R	0.999
8:94823510:T:C	F27L	0.999
8:94823511:T:C	F27S	0.999
8:94823512:T:A	F27L	0.999
8:94823512:T:G	F27L	0.999
8:94824911:T:C	L50P	0.999
8:94824923:T:C	F54S	0.999
8:94824993:A:C	R77S	0.999
8:94824993:A:T	R77S	0.999
8:94825016:C:A	A85D	0.999
8:94827289:T:C	L111P	0.999
8:94827292:T:C	L112P	0.999
8:94827301:T:C	L115P	0.999
8:94827312:A:C	S119R	0.999
8:94827314:T:A	S119R	0.999
8:94827314:T:G	S119R	0.999
8:94851592:T:A	L516H	0.999
8:94853807:G:C	W548C	0.999

dbSNP variants (sampled 300 via entrez): RS1000049769 (8:94877354 A>G), RS1000086081 (8:94836955 C>T), RS1000096600 (8:94822323 AG>A), RS1000133842 (8:94851596 A>G), RS1000183358 (8:94843299 G>A), RS1000254127 (8:94844314 C>G), RS1000256977 (8:94843049 C>G,T), RS1000329981 (8:94848624 T>C), RS1000507908 (8:94832454 A>G), RS1000513016 (8:94854369 C>A,T), RS1000554388 (8:94861763 G>A), RS1000566314 (8:94871322 A>G), RS1000590760 (8:94861215 T>C), RS1000733174 (8:94877834 G>A,C), RS1000784926 (8:94826774 T>C)

Disease associations

OMIM: gene MIM:611351 | disease phenotypes: MIM:618572

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with cerebellar hypoplasia and spasticity	Limited	Unknown

Mondo (3): neurodevelopmental disorder with cerebellar hypoplasia and spasticity (MONDO:0032818), prostate cancer (MONDO:0008315), long QT syndrome (MONDO:0002442)

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

HPO phenotypes

14 total (14 of 14 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000316	Hypertelorism
HP:0000648	Optic atrophy
HP:0001250	Seizure
HP:0001258	Spastic paraplegia
HP:0001263	Global developmental delay
HP:0001321	Cerebellar hypoplasia
HP:0001344	Absent speech
HP:0001845	Overlapping toe
HP:0002057	Prominent glabella
HP:0002540	Inability to walk
HP:0004322	Short stature
HP:0032388	Periventricular nodular heterotopia

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002560_14	Type 2 diabetes	1.000000e-07
GCST002560_6	Type 2 diabetes	1.000000e-07
GCST002937_3	Molybdenum levels	4.000000e-07
GCST009597_95	Multiple sclerosis	3.000000e-10
GCST90002390_606	Mean corpuscular hemoglobin	2.000000e-12
GCST90002392_587	Mean corpuscular volume	4.000000e-12
GCST90013442_10	Keratoconus	3.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004527	mean corpuscular hemoglobin

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547
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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724658 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance	2
Valproic Acid	affects expression, decreases expression	2
TAK-243	increases sumoylation	1
ginger extract	decreases reaction, increases abundance, decreases expression	1
dicrotophos	decreases expression	1
alpha-pinene	affects expression, increases abundance, affects cotreatment	1
bisphenol A	increases abundance, decreases expression, decreases reaction	1
salinomycin	decreases expression	1
arsenite	affects binding, decreases reaction	1
methylparaben	increases expression	1
benzo(e)pyrene	decreases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
methacrylaldehyde	affects expression, increases abundance, affects cotreatment	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
abrine	decreases expression	1
jinfukang	decreases expression	1
Acrolein	affects cotreatment, affects expression, increases abundance	1
Air Pollutants	affects expression, increases abundance, affects cotreatment	1
Arsenic	decreases expression, increases abundance	1
Doxorubicin	decreases expression	1
Lead	affects expression	1
Methapyrilene	decreases methylation	1
Oils, Volatile	decreases expression, decreases reaction, increases abundance	1
Ozone	affects cotreatment, affects expression, increases abundance	1
Quercetin	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	increases methylation	1
Volatile Organic Compounds	affects cotreatment, affects 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
CHEMBL5697463	Binding	Inhibition of INTS8 (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)

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