INTS15

Summary

INTS15 (integrator complex subunit 15, HGNC:21702) is a protein-coding gene on chromosome 7p22.1, encoding Integrator complex subunit 15 (Q96N11). 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 selective cancer dependency (DepMap: 52.0% of cell lines).

Predicted to act upstream of or within brain development; eye development; and mRNA splicing, via spliceosome. Part of integrator complex. Is active in nucleus.

Source: NCBI Gene 79034 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 26 total
• Cancer dependency (DepMap): dependent in 52.0% of screened cell lines
• MANE Select transcript: NM_024067

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21702
Approved symbol	INTS15
Name	integrator complex subunit 15
Location	7p22.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC2718
Ensembl gene	ENSG00000146576
Ensembl biotype	protein_coding
OMIM	621239
Entrez	79034

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000344417, ENST00000359073, ENST00000440409, ENST00000445375, ENST00000472693, ENST00000477298, ENST00000898722, ENST00000898723, ENST00000898724, ENST00000898725, ENST00000898726, ENST00000934781

RefSeq mRNA: 2 — MANE Select: NM_024067 NM_001303039, NM_024067

CCDS: CCDS5353, CCDS78206

Canonical transcript exons

ENST00000344417 — 6 exons

Exon	Start	End
ENSE00000976381	6591646	6591867
ENSE00000976382	6594435	6594600
ENSE00001846999	6590021	6590475
ENSE00001957463	6607960	6608726
ENSE00003465077	6599829	6600356
ENSE00003617287	6602101	6602140

Expression profiles

Bgee: expression breadth ubiquitous, 265 present calls, max score 92.48.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.3618 / max 148.7481, expressed in 1807 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
77157	11.6432	1797
77160	2.0934	1257
77159	1.7763	1209
77158	1.3831	1055
77156	0.4658	238

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	92.48	gold quality
endocervix	UBERON:0000458	91.78	gold quality
left uterine tube	UBERON:0001303	91.69	gold quality
cortical plate	UBERON:0005343	91.63	gold quality
body of uterus	UBERON:0009853	91.36	gold quality
mucosa of stomach	UBERON:0001199	91.27	gold quality
ganglionic eminence	UBERON:0004023	91.06	gold quality
right lobe of thyroid gland	UBERON:0001119	90.81	gold quality
body of stomach	UBERON:0001161	90.76	gold quality
spleen	UBERON:0002106	90.76	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.64	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	90.52	gold quality
lower esophagus muscularis layer	UBERON:0035833	90.46	gold quality
lower esophagus	UBERON:0013473	90.42	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.37	gold quality
tibial nerve	UBERON:0001323	90.32	gold quality
cerebellar hemisphere	UBERON:0002245	90.21	gold quality
right uterine tube	UBERON:0001302	90.20	gold quality
secondary oocyte	CL:0000655	90.12	gold quality
apex of heart	UBERON:0002098	90.10	gold quality
right ovary	UBERON:0002118	90.08	gold quality
left lobe of thyroid gland	UBERON:0001120	90.06	gold quality
cerebellar cortex	UBERON:0002129	90.01	gold quality
gall bladder	UBERON:0002110	89.94	gold quality
right coronary artery	UBERON:0001625	89.91	gold quality
popliteal artery	UBERON:0002250	89.87	gold quality
tibial artery	UBERON:0007610	89.86	gold quality
body of pancreas	UBERON:0001150	89.84	gold quality
aorta	UBERON:0000947	89.70	gold quality
thoracic aorta	UBERON:0001515	89.69	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.85

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

23 targeting INTS15, 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-4282	99.99	75.36	6408
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-5580-3P	99.70	69.41	2052
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-488-3P	99.61	68.79	1731
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-6829-5P	98.86	65.12	1480
HSA-MIR-6730-5P	98.03	68.12	1299
HSA-MIR-5681A	97.99	67.17	1658
HSA-MIR-6787-5P	97.54	63.85	457

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 52.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• Integrator complex subunit 15 controls mRNA splicing and is critical for eye development. (PMID:36851842)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ints15	ENSDARG00000037652
mus_musculus	Ints15	ENSMUSG00000039244
rattus_norvegicus	Ints15	ENSRNOG00000024567
drosophila_melanogaster	CG5274	FBGN0036987
caenorhabditis_elegans		WBGENE00013243

Protein

Protein identifiers

Integrator complex subunit 15 — Q96N11 (reviewed: Q96N11)

All UniProt accessions (3): Q96N11, H7BZK9, H7C0Q5

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). INTS15 is part of the integrator tail module that acts as a platform for the recruitment of transcription factors at promoters. Within the integrator complex, INTS15 is required to bridge different integrator modules.

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. INTS15 is part of the tail subcomplex, composed of INTS10, INTS13, INTS14 and INTS15.

Subcellular location. Nucleus. Chromosome.

Similarity. Belongs to the Integrator subunit 15 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96N11-1	1	yes
Q96N11-2	2

RefSeq proteins (2): NP_001289968, NP_076972* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027844	INTS15	Family

Pfam: PF14964

UniProt features (39 total): helix 23, turn 6, strand 3, mutagenesis site 3, splice variant 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
8RC4	ELECTRON MICROSCOPY	3.1
9EP4	ELECTRON MICROSCOPY	3.2
8RBZ	ELECTRON MICROSCOPY	3.7
9EP1	ELECTRON MICROSCOPY	4
9FA4	ELECTRON MICROSCOPY	4
9FA7	ELECTRON MICROSCOPY	4
8RBX	ELECTRON MICROSCOPY	4.1
9EOF	ELECTRON MICROSCOPY	7.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96N11-F1	83.07	0.69

Functional residue map

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

Mutagenesis-validated functional residues (3):

Position	Phenotype
69–72	abolished intraction with ints5, leading to impaired assembly of the integrator complex.
120–124	abolished intraction with ints5, leading to impaired assembly of the integrator complex.
384–387	abolished interaction with ints10.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 88 (showing top): GOBP_MACROMOLECULE_CATABOLIC_PROCESS, chr7p22, GTGCCTT_MIR506, GOBP_RNA_SURVEILLANCE, GOBP_RNA_SPLICING, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GOBP_TRANSCRIPTION_INITIATION_AT_RNA_POLYMERASE_II_PROMOTER, GOBP_HEAD_DEVELOPMENT, GOBP_SENSORY_ORGAN_DEVELOPMENT, GOBP_SNRNA_PROCESSING, GOBP_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_ELONGATION, GINESTIER_BREAST_CANCER_ZNF217_AMPLIFIED_DN, GOCC_INTEGRATOR_COMPLEX, GOBP_DNA_TEMPLATED_TRANSCRIPTION_ELONGATION, BILANGES_SERUM_SENSITIVE_VIA_TSC2

GO Biological Process (4): mRNA splicing, via spliceosome (GO:0000398), eye development (GO:0001654), brain development (GO:0007420), RNA polymerase II transcription initiation surveillance (GO:0160240)

GO Molecular Function (0):

GO Cellular Component (4): nucleus (GO:0005634), chromosome (GO:0005694), integrator complex (GO:0032039), INTAC complex (GO:0160232)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear protein-containing complex	2
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
sensory organ development	1
visual system development	1
central nervous system development	1
animal organ development	1
head development	1
transcription initiation at RNA polymerase II promoter	1
nuclear RNA surveillance	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
integrator complex	1

Protein interactions and networks

STRING

650 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
INTS15	INTS14	Q96SY0	668
INTS15	MRM2	Q9UI43	503
INTS15	HERPUD2	Q9BSE4	499
INTS15	FBXO42	Q6P3S6	487
INTS15	NUDCD3	Q8IVD9	480
INTS15	ZDHHC4	Q9NPG8	471
INTS15	TMEM242	Q9NWH2	447
INTS15	PABIR1	Q96E09	446
INTS15	VOPP1	Q96AW1	439
INTS15	FAM220A	Q7Z4H9	434
INTS15	INTS6L	Q5JSJ4	398
INTS15	AFG2B	Q9BVQ7	397
INTS15	NAIF1	Q69YI7	383
INTS15	RNF216	Q9NWF9	371
INTS15	CCDC86	Q9H6F5	370
INTS15	ZNF12	P17014	370

IntAct

16 interactions, top by confidence:

A	B	Type	Score
SUPT5H	POLR2D	psi-mi:“MI:0914”(association)	0.530
INTS15	H1-5	psi-mi:“MI:0915”(physical association)	0.400
INTS15	H1-2	psi-mi:“MI:0915”(physical association)	0.400
INTS15	HSPA8	psi-mi:“MI:0915”(physical association)	0.400
INTS15	E6	psi-mi:“MI:0915”(physical association)	0.370
MKI67	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
INTS10	TUBB	psi-mi:“MI:0914”(association)	0.350
HDGF	KIF2A	psi-mi:“MI:0914”(association)	0.350
POLR2B	PALM3	psi-mi:“MI:0914”(association)	0.350
POLR2F	BDP1	psi-mi:“MI:0914”(association)	0.350
PPP2CA	SUPT5H	psi-mi:“MI:0914”(association)	0.350
SSRP1	DDX39A	psi-mi:“MI:0914”(association)	0.350
INTS15	AK5	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (32): C7orf26 (Co-fractionation), C7orf26 (Co-fractionation), C7orf26 (Co-fractionation), C7orf26 (Co-fractionation), INTS5 (Co-fractionation), INTS8 (Co-fractionation), C7orf26 (Affinity Capture-MS), AK5 (Two-hybrid), C7orf26 (Proximity Label-MS), C7orf26 (Proximity Label-MS), C7orf26 (Affinity Capture-MS), C7orf26 (Affinity Capture-MS), HSPA8 (Affinity Capture-MS), C7orf26 (Affinity Capture-MS), C7orf26 (Negative Genetic)

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: Q7ZTY6, Q8BGA7, Q96N11

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 22 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
Pausing and recovery of Tat-mediated HIV elongation	5	96.9×	1e-07
Tat-mediated HIV elongation arrest and recovery	5	96.9×	1e-07
HIV elongation arrest and recovery	5	91.1×	1e-07
Pausing and recovery of HIV elongation	5	91.1×	1e-07
HIV Transcription Elongation	5	88.4×	1e-07
Formation of HIV-1 elongation complex containing HIV-1 Tat	5	68.3×	3e-07
Tat-mediated elongation of the HIV-1 transcript	5	68.3×	3e-07
Formation of HIV elongation complex in the absence of HIV Tat	5	65.3×	3e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	9
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1514 predictions. Top by Δscore:

Variant	Effect	Δscore
7:6590472:CAAGG:C	donor_loss	1.0000
7:6591864:TCAG:T	donor_loss	1.0000
7:6591865:CAG:C	donor_loss	1.0000
7:6591866:AGG:A	donor_loss	1.0000
7:6591867:GGTAC:G	donor_loss	1.0000
7:6591869:T:G	donor_loss	1.0000
7:6599823:TTGCA:T	acceptor_loss	1.0000
7:6599824:TGCA:T	acceptor_loss	1.0000
7:6599825:GCAG:G	acceptor_loss	1.0000
7:6599826:CAG:C	acceptor_loss	1.0000
7:6599827:A:AG	acceptor_gain	1.0000
7:6599827:AGA:A	acceptor_loss	1.0000
7:6599828:G:GG	acceptor_gain	1.0000
7:6599828:GAT:G	acceptor_gain	1.0000
7:6600278:GAGAT:G	donor_gain	1.0000
7:6600354:GAG:G	donor_gain	1.0000
7:6600355:AG:A	donor_loss	1.0000
7:6600356:GGTG:G	donor_loss	1.0000
7:6600357:GTGG:G	donor_loss	1.0000
7:6602137:ATAA:A	donor_gain	1.0000
7:6602138:TAAGT:T	donor_loss	1.0000
7:6602140:AGTA:A	donor_loss	1.0000
7:6602141:G:GG	donor_gain	1.0000
7:6590456:A:T	donor_gain	0.9900
7:6591644:A:AG	acceptor_gain	0.9900
7:6591645:G:GG	acceptor_gain	0.9900
7:6591645:GA:G	acceptor_gain	0.9900
7:6591839:TGTTG:T	donor_gain	0.9900
7:6591840:GTTGG:G	donor_gain	0.9900
7:6594433:A:AG	acceptor_gain	0.9900

AlphaMissense

2916 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:6591668:T:C	L72P	1.000
7:6591674:T:C	L74P	1.000
7:6591803:T:C	L117P	1.000
7:6591814:G:C	A121P	1.000
7:6599984:T:A	W246R	1.000
7:6599984:T:C	W246R	1.000
7:6607971:T:C	L387P	1.000
7:6590306:T:C	L8P	0.999
7:6590330:C:A	A16D	0.999
7:6590333:C:A	A17D	0.999
7:6590338:G:A	E19K	0.999
7:6590434:T:C	F51L	0.999
7:6590436:C:A	F51L	0.999
7:6590436:C:G	F51L	0.999
7:6591677:T:C	L75P	0.999
7:6591815:C:A	A121E	0.999
7:6591821:C:A	A123D	0.999
7:6591859:T:A	W136R	0.999
7:6591859:T:C	W136R	0.999
7:6591863:T:C	L137P	0.999
7:6594540:A:C	S174R	0.999
7:6594542:C:A	S174R	0.999
7:6594542:C:G	S174R	0.999
7:6599873:T:A	W209R	0.999
7:6599873:T:C	W209R	0.999
7:6600117:T:C	L290P	0.999
7:6600132:T:C	L295P	0.999
7:6600294:T:C	L349P	0.999
7:6600300:G:C	R351P	0.999
7:6600303:T:C	L352P	0.999

dbSNP variants (sampled 300 via entrez): RS1000049522 (7:6599365 A>C), RS1000133121 (7:6596493 C>G,T), RS1000196336 (7:6591045 C>G), RS1000314922 (7:6590875 G>A,T), RS1000343281 (7:6604291 G>A), RS1000356215 (7:6600708 A>C), RS1000446454 (7:6595077 G>C), RS1000577537 (7:6592959 A>G), RS1000630803 (7:6588172 C>T), RS1000658504 (7:6588393 C>T), RS1000786902 (7:6607905 C>A,T), RS1001239644 (7:6590972 G>T), RS1001328481 (7:6601573 G>A), RS1001704181 (7:6596086 C>G), RS1001730277 (7:6595247 G>C)

Disease associations

OMIM: gene MIM:621239 | 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
GCST005951_155	Body mass index	1.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	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	decreases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Adenine	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Cisplatin	decreases expression	1
Colchicine	decreases expression	1
Ethyl Methanesulfonate	decreases expression	1
Etoposide	decreases expression	1
Hydroxyurea	decreases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Methyl Methanesulfonate	decreases expression	1
Selenium	increases expression	1
Smoke	decreases expression	1
Tretinoin	decreases expression	1
Urethane	increases expression	1
Vitamin E	increases expression	1
Mitomycin	decreases expression	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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