INTS9

Summary

INTS9 (integrator complex subunit 9, HGNC:25592) is a protein-coding gene on chromosome 8p21.1, encoding Integrator complex subunit 9 (Q9NV88). 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 99.9% of cancer cell lines).

This gene encodes a subunit of the Integrator complex. This protein complex binds the C-terminal domain of RNA polymerase II and likely plays a role in small nuclear RNA processing. The encoded protein has similarities to the subunits of the cleavage and polyadenylation specificity factor complex. Alternatively spliced transcript variants have been described.

Source: NCBI Gene 55756 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 111 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.9% of screened cell lines (common-essential)
• MANE Select transcript: NM_018250

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25592
Approved symbol	INTS9
Name	integrator complex subunit 9
Location	8p21.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10871, CPSF2L, RC-74
Ensembl gene	ENSG00000104299
Ensembl biotype	protein_coding
OMIM	611352
Entrez	55756

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 15 protein_coding, 6 retained_intron, 4 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000416984, ENST00000517383, ENST00000518510, ENST00000519578, ENST00000520005, ENST00000520184, ENST00000520316, ENST00000520437, ENST00000520831, ENST00000520983, ENST00000521022, ENST00000521070, ENST00000521777, ENST00000522074, ENST00000522363, ENST00000523076, ENST00000523303, ENST00000523436, ENST00000524081, ENST00000867977, ENST00000917294, ENST00000967871, ENST00000967872, ENST00000967873, ENST00000967874, ENST00000967875, ENST00000967876

RefSeq mRNA: 4 — MANE Select: NM_018250 NM_001145159, NM_001172562, NM_001363038, NM_018250

CCDS: CCDS34873, CCDS55215, CCDS55216

Canonical transcript exons

ENST00000521022 — 17 exons

Exon	Start	End
ENSE00002113790	28889874	28889969
ENSE00003461876	28777829	28777953
ENSE00003471896	28787829	28787889
ENSE00003473498	28859436	28859563
ENSE00003481018	28767661	28768322
ENSE00003491436	28813492	28813612
ENSE00003505359	28769889	28770026
ENSE00003508911	28796544	28796655
ENSE00003564055	28780823	28780994
ENSE00003564729	28775759	28775926
ENSE00003573668	28835292	28835378
ENSE00003597610	28770982	28771080
ENSE00003604197	28850213	28850273
ENSE00003616727	28812327	28812461
ENSE00003645929	28837637	28837776
ENSE00003687189	28846747	28846809
ENSE00003786663	28793807	28793987

Expression profiles

Bgee: expression breadth ubiquitous, 230 present calls, max score 93.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.1988 / max 142.4192, expressed in 1796 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92543	13.8615	1795
92544	0.2271	106
92545	0.0740	28
92542	0.0363	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	93.14	gold quality
oocyte	CL:0000023	92.53	gold quality
right adrenal gland	UBERON:0001233	90.55	gold quality
right adrenal gland cortex	UBERON:0035827	90.38	gold quality
left adrenal gland	UBERON:0001234	90.36	gold quality
left adrenal gland cortex	UBERON:0035825	90.27	gold quality
apex of heart	UBERON:0002098	89.88	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.93	gold quality
adrenal gland	UBERON:0002369	88.67	gold quality
adrenal cortex	UBERON:0001235	88.63	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.70	gold quality
granulocyte	CL:0000094	87.20	gold quality
buccal mucosa cell	CL:0002336	87.18	gold quality
lower esophagus mucosa	UBERON:0035834	87.16	gold quality
adenohypophysis	UBERON:0002196	86.99	gold quality
right uterine tube	UBERON:0001302	86.75	gold quality
cortical plate	UBERON:0005343	86.32	gold quality
right lobe of thyroid gland	UBERON:0001119	86.14	gold quality
spleen	UBERON:0002106	85.98	gold quality
mucosa of transverse colon	UBERON:0004991	85.64	gold quality
colonic epithelium	UBERON:0000397	85.35	gold quality
left lobe of thyroid gland	UBERON:0001120	85.19	gold quality
islet of Langerhans	UBERON:0000006	85.03	gold quality
pituitary gland	UBERON:0000007	84.96	gold quality
monocyte	CL:0000576	84.82	gold quality
adrenal tissue	UBERON:0018303	84.79	gold quality
leukocyte	CL:0000738	84.75	gold quality
mononuclear cell	CL:0000842	84.50	gold quality
gastrocnemius	UBERON:0001388	84.39	gold quality
tibial nerve	UBERON:0001323	84.36	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.69
E-MTAB-7303	no	241.34
E-MTAB-4850	no	92.36

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting INTS9, 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-3163	100.00	77.23	8605
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-1324	99.46	66.57	1302
HSA-MIR-1273H-3P	99.29	67.55	980
HSA-MIR-4293	99.22	65.46	1263
HSA-MIR-3199	99.17	65.19	696
HSA-MIR-8052	99.17	65.01	719
HSA-MIR-1253	99.12	67.08	1688
HSA-MIR-3166	98.24	66.63	1223
HSA-MIR-5681A	97.99	67.17	1658
HSA-MIR-483-3P	97.77	64.95	731
HSA-MIR-450B-3P	97.56	66.12	512
HSA-MIR-10400-3P	97.29	64.66	597
HSA-MIR-4674	97.29	64.62	597
HSA-MIR-769-3P	97.06	64.83	464
HSA-MIR-12128	96.67	66.98	1471
HSA-MIR-6806-5P	96.37	68.74	587
HSA-MIR-6865-5P	96.05	65.58	675

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.9% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 3)

• The specific heterodimeric interaction between IntS9 and IntS11 is mediated by a discrete domain present at the extreme C terminus of IntS9 and within the C terminus of IntS11, adjacent to the predicted active site of this endonuclease. (PMID:22252320)
• Functional studies demonstrate that the IntS9-IntS11 interaction is crucial for the role of INT in snRNA 3’-end processing. (PMID:28396433)
• INTS4 is a specific and conserved interaction partner of INTS9/11 that does not interact with either subunit individually. (PMID:29471365)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ints9	ENSDARG00000067913
mus_musculus	Ints9	ENSMUSG00000021975
rattus_norvegicus	Ints9	ENSRNOG00000013459
drosophila_melanogaster	IntS9	FBGN0036570
caenorhabditis_elegans		WBGENE00017608

Paralogs (3): CPSF3 (ENSG00000119203), INTS11 (ENSG00000127054), CPSF2 (ENSG00000165934)

Protein

Protein identifiers

Integrator complex subunit 9 — Q9NV88 (reviewed: Q9NV88)

Alternative names: Protein related to CPSF subunits of 74 kDa

All UniProt accessions (9): E5RG70, E5RGY2, E5RJ88, E5RK47, Q9NV88, G3XAN1, H0YBH8, H0YBK3, H0YBQ3

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). Mediates recruitment of cytoplasmic dynein to the nuclear envelope, probably as component of the integrator complex.

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. INTS9 is part of the RNA endonuclease subcomplex, composed of INTS4, INTS9, INTS11 and inositol hexakisphosphate (InsP6). Interacts with WDR73; interaction is required for the assembly of the RNA endonuclease subcomplex in the cytoplasm. Interacts with BRAT1; interaction is required for the assembly of the RNA endonuclease subcomplex. Interacts with ESRRB, ESRRB is not a core component of the Integrator complex and this association is a bridge for the interaction with the multiprotein complex Integrator; attracts the transcriptional machinery.

Subcellular location. Nucleus. Cytoplasm.

Miscellaneous. Although strongly related to RNA-specific endonuclease proteins, it lacks the HXHXDH motif that binds zinc and participates in the catalytic center. Its function as endonuclease is therefore unsure.

Similarity. Belongs to the metallo-beta-lactamase superfamily. RNA-metabolizing metallo-beta-lactamase-like family. INTS9 subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9NV88-1	1	yes
Q9NV88-2	2
Q9NV88-3	3

RefSeq proteins (4): NP_001138631, NP_001166033, NP_001349967, NP_060720* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001279	Metallo-B-lactamas	Domain
IPR022712	Beta_Casp	Domain
IPR027074	Integrator_9su	Family
IPR036866	RibonucZ/Hydroxyglut_hydro	Homologous_superfamily
IPR048660	IntS9-like_C	Domain

Pfam: PF10996, PF16661, PF21382

UniProt features (93 total): strand 42, helix 27, mutagenesis site 7, turn 6, binding site 4, splice variant 2, chain 1, region of interest 1, sequence conflict 1, short sequence motif 1, cross-link 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
5V8W	X-RAY DIFFRACTION	2.1
8RC4	ELECTRON MICROSCOPY	3.1
8R23	ELECTRON MICROSCOPY	3.2
8UIB	ELECTRON MICROSCOPY	3.21
7CUN	ELECTRON MICROSCOPY	3.5
7BFP	ELECTRON MICROSCOPY	3.56
7PKS	ELECTRON MICROSCOPY	3.6
8RBZ	ELECTRON MICROSCOPY	3.7
8R22	ELECTRON MICROSCOPY	3.9
8R2D	ELECTRON MICROSCOPY	3.9
8RBX	ELECTRON MICROSCOPY	4.1
8YJB	ELECTRON MICROSCOPY	4.1
7BFQ	ELECTRON MICROSCOPY	4.15
7YCX	ELECTRON MICROSCOPY	4.18
9VD9	ELECTRON MICROSCOPY	4.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NV88-F1	90.95	0.76

Functional residue map

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

Ligand- & substrate-binding residues (4): 2; 19; 510; 511

Post-translational modifications (1): 58

Mutagenesis-validated functional residues (7):

Position	Phenotype
280–290	abolished interaction with brat1.
283	abolished interaction with brat1.
283	decreased interaction with ints11 and brat1.
566–570	decreased localization in the nucleus.
633–635	abolished interaction with ints11.
644–648	abolished interaction with ints11.
644	abolished interaction with ints11.

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: 205 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, RRAGTTGT_UNKNOWN, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, CMYB_01, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GGGTGGRR_PAX4_03, AACWWCAANK_UNKNOWN, IRF7_01, GOBP_RNA_SURVEILLANCE, chr8p21, MARTINEZ_RB1_TARGETS_DN, GOBP_REGULATION_OF_TRANSMEMBRANE_RECEPTOR_PROTEIN_SERINE_THREONINE_KINASE_SIGNALING_PATHWAY, GOBP_RESPONSE_TO_TRANSFORMING_GROWTH_FACTOR_BETA

GO Biological Process (7): snRNA processing (GO:0016180), negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512), regulation of transcription elongation by RNA polymerase II (GO:0034243), snRNA 3’-end processing (GO:0034472), RNA polymerase II transcription initiation surveillance (GO:0160240), negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway (GO:0090101), regulation of cellular response to growth factor stimulus (GO:0090287)

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

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), integrator complex (GO:0032039), INTAC complex (GO:0160232)

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	3
nuclear protein-containing complex	2
RNA processing	1
snRNA metabolic process	1
transforming growth factor beta receptor signaling pathway	1
regulation of transforming growth factor beta receptor signaling pathway	1
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
transcription elongation by RNA polymerase II	1
regulation of DNA-templated transcription elongation	1
snRNA processing	1
RNA 3’-end processing	1
transcription initiation at RNA polymerase II promoter	1
nuclear RNA surveillance	1
cell surface receptor protein serine/threonine kinase signaling pathway	1
negative regulation of signal transduction	1
regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
regulation of response to stimulus	1
cellular response to growth factor stimulus	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
integrator complex	1

Protein interactions and networks

STRING

1470 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
INTS9	INTS11	Q5TA45	951
INTS9	INTS4	Q96HW7	937
INTS9	INTS10	Q9NVR2	901
INTS9	INTS5	Q6P9B9	897
INTS9	INTS7	Q9NVH2	893
INTS9	INTS1	Q8N201	887
INTS9	INTS8	Q75QN2	884
INTS9	INTS3	Q68E01	861
INTS9	INTS12	Q96CB8	852
INTS9	LACTB	P83096	762
INTS9	INTS13	Q9NVM9	745
INTS9	INTS2	Q9H0H0	719
INTS9	POLR2A	P24928	708
INTS9	SEM1	Q6ZVN7	696
INTS9	KPNA2	P52292	660

IntAct

68 interactions, top by confidence:

A	B	Type	Score
INTS11	INTS9	psi-mi:“MI:0407”(direct interaction)	0.940
INTS11	INTS9	psi-mi:“MI:0915”(physical association)	0.940
INTS9	INTS11	psi-mi:“MI:0915”(physical association)	0.940
INTS9	INTS11	psi-mi:“MI:0914”(association)	0.940
PPP2R1A	STRN	psi-mi:“MI:0914”(association)	0.880
INTS11	INTS4	psi-mi:“MI:0915”(physical association)	0.860
INTS10	INTS11	psi-mi:“MI:0915”(physical association)	0.740
INTS13	INTS11	psi-mi:“MI:0915”(physical association)	0.690
INTS4	INTS9	psi-mi:“MI:0915”(physical association)	0.680
CETN1	SFI1	psi-mi:“MI:0914”(association)	0.640
DNAJC7	PLD2	psi-mi:“MI:0914”(association)	0.640
KPNA1	TCERG1	psi-mi:“MI:0914”(association)	0.640

BioGRID (108): CPSF3L (Co-fractionation), INTS5 (Co-fractionation), INTS9 (Co-fractionation), INTS9 (Proximity Label-MS), INTS9 (Affinity Capture-MS), INTS9 (Affinity Capture-MS), INTS9 (Affinity Capture-MS), INTS9 (Affinity Capture-MS), INTS9 (Affinity Capture-MS), INTS9 (Affinity Capture-MS), INTS9 (Affinity Capture-MS), INTS9 (Affinity Capture-MS), INTS9 (Affinity Capture-MS), INTS9 (Affinity Capture-MS), INTS9 (Affinity Capture-MS)

ESM2 similar proteins: A4F267, A6QR22, E9PZQ0, F1LMY4, O70422, O96008, P07144, P11716, P16960, P21817, P42054, P42055, P42056, P45880, P46274, P60027, P68002, P68003, P81155, P82013, P86223, Q0JNK5, Q1LZB5, Q29380, Q53PC7, Q5E9L7, Q5R7V4, Q5U3I0, Q60930, Q60931, Q6K548, Q6P825, Q75Q40, Q7F4F8, Q7ZTM6, Q91W86, Q920Q4, Q92759, Q969M1, Q9CZR3

Diamond homologs: A7SBF0, Q2KJA6, Q4R5Z4, Q54SH0, Q5ZKK2, Q6DFF4, Q8K114, Q95TS5, Q9NV88

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
INTS9	“form complex”	“Integrator complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 68 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	8	108.8×	4e-14
Abortive elongation of HIV-1 transcript in the absence of Tat	10	88.7×	3e-16
Signaling by FGFR2 IIIa TM	8	85.9×	3e-13
Pausing and recovery of Tat-mediated HIV elongation	11	72.4×	2e-16
Tat-mediated HIV elongation arrest and recovery	11	72.4×	2e-16
HIV elongation arrest and recovery	11	68.0×	3e-16
Pausing and recovery of HIV elongation	11	68.0×	3e-16
HIV Transcription Elongation	11	66.0×	3e-16

GO biological processes:

GO term	Partners	Fold	FDR
RNA polymerase II transcription initiation surveillance	9	128.8×	3e-15
snRNA processing	7	118.9×	1e-11
regulation of transcription elongation by RNA polymerase II	8	103.5×	9e-13
transcription by RNA polymerase II	9	10.2×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	88
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3191 predictions. Top by Δscore:

Variant	Effect	Δscore
8:28768321:TG:T	acceptor_gain	1.0000
8:28768329:C:CT	acceptor_gain	1.0000
8:28768329:C:T	acceptor_gain	1.0000
8:28768330:A:T	acceptor_gain	1.0000
8:28769883:GCTCA:G	donor_loss	1.0000
8:28769884:CTCA:C	donor_loss	1.0000
8:28769885:TCAC:T	donor_loss	1.0000
8:28769886:CACCT:C	donor_loss	1.0000
8:28769887:A:T	donor_loss	1.0000
8:28769888:CCTT:C	donor_gain	1.0000
8:28770022:GGGGG:G	acceptor_gain	1.0000
8:28770023:GGGG:G	acceptor_gain	1.0000
8:28770024:GGG:G	acceptor_gain	1.0000
8:28770025:GG:G	acceptor_gain	1.0000
8:28770025:GGC:G	acceptor_loss	1.0000
8:28770027:C:CC	acceptor_gain	1.0000
8:28770033:C:CT	acceptor_gain	1.0000
8:28770034:A:T	acceptor_gain	1.0000
8:28770976:CCCTA:C	donor_loss	1.0000
8:28770977:CCTA:C	donor_loss	1.0000
8:28770978:CTA:C	donor_loss	1.0000
8:28770979:TA:T	donor_loss	1.0000
8:28770980:A:C	donor_loss	1.0000
8:28770981:C:CG	donor_loss	1.0000
8:28771001:T:C	donor_gain	1.0000
8:28775755:TCACC:T	donor_loss	1.0000
8:28775756:CA:C	donor_loss	1.0000
8:28775757:A:AT	donor_loss	1.0000
8:28775758:CCT:C	donor_gain	1.0000
8:28775927:C:CC	acceptor_gain	1.0000

AlphaMissense

4314 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:28768273:A:T	V617D	1.000
8:28777881:A:T	I448N	1.000
8:28780831:A:T	I421K	1.000
8:28780834:A:T	V420D	1.000
8:28780859:A:G	W412R	1.000
8:28780859:A:T	W412R	1.000
8:28780885:C:A	G403V	1.000
8:28780885:C:T	G403E	1.000
8:28780886:C:A	G403W	1.000
8:28780886:C:G	G403R	1.000
8:28780886:C:T	G403R	1.000
8:28780891:C:G	R401P	1.000
8:28780912:A:G	F394S	1.000
8:28780975:A:G	L373P	1.000
8:28787842:A:G	F362S	1.000
8:28787887:A:G	L347P	1.000
8:28793808:A:G	W346R	1.000
8:28793808:A:T	W346R	1.000
8:28793846:G:T	A333D	1.000
8:28793921:A:G	L308P	1.000
8:28793924:T:A	D307V	1.000
8:28793924:T:G	D307A	1.000
8:28793951:G:T	P298H	1.000
8:28793954:A:T	V297D	1.000
8:28812335:G:C	H246D	1.000
8:28812398:A:G	W225R	1.000
8:28812398:A:T	W225R	1.000
8:28812405:G:C	S222R	1.000
8:28812405:G:T	S222R	1.000
8:28812407:T:G	S222R	1.000

dbSNP variants (sampled 300 via entrez): RS1000036494 (8:28866050 T>A,C), RS1000065775 (8:28872593 A>G), RS1000066271 (8:28776939 G>A,C), RS1000066954 (8:28810070 ATTTC>A), RS1000117850 (8:28813699 C>A,T), RS1000178731 (8:28829692 G>A), RS1000238374 (8:28780869 G>C), RS1000287588 (8:28770561 C>G), RS1000292560 (8:28782525 ATG>A), RS1000298458 (8:28775645 C>T), RS1000325657 (8:28775867 C>T), RS1000382122 (8:28822853 T>A), RS1000391475 (8:28868918 G>T), RS1000418379 (8:28873023 A>G), RS1000436655 (8:28855298 C>A,T)

Disease associations

OMIM: gene MIM:611352 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007202_1	High density lipoprotein cholesterol levels	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724660 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

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

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.00	IC50	1e+04	nM	MOLIBRESIB

PubChem BioAssay actives

1 with measured affinity, of 6 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178698: Inhibition of INTS9 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases methylation, affects methylation	5
sodium arsenite	affects methylation, decreases expression	2
Lead	affects expression, decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
FR900359	decreases phosphorylation	1
2,4,6-tribromophenol	decreases expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	increases expression	1
decabromobiphenyl ether	decreases expression	1
arsenite	affects binding, decreases reaction	1
tetrabromobisphenol A	decreases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
aflatoxin B2	affects methylation	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
Sunitinib	decreases expression	1
Atrazine	decreases expression	1
Cisplatin	decreases expression	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Methapyrilene	increases methylation	1
Rotenone	decreases expression	1
Testosterone	increases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Cyclosporine	decreases 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
CHEMBL5697428	Binding	Inhibition of INTS9 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Clinical trials (associated diseases)

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