INTS5

Summary

INTS5 (integrator complex subunit 5, HGNC:29352) is a protein-coding gene on chromosome 11q12.3, encoding Integrator complex subunit 5 (Q6P9B9). 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 98.1% of cancer cell lines).

The Integrator complex is a complex that associates with the C-terminal domain of RNA polymerase II large subunit. This complex is brought to U1 and U2 small nuclear RNA genes, where it is involved in the transcription and processing of their transcripts. The protein encoded by this gene represents a subunit of the Integrator complex.

Source: NCBI Gene 80789 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 133 total
• Cancer dependency (DepMap): dependent in 98.1% of screened cell lines (common-essential)
• MANE Select transcript: NM_030628

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29352
Approved symbol	INTS5
Name	integrator complex subunit 5
Location	11q12.3
Locus type	gene with protein product
Status	Approved
Aliases	INT5
Ensembl gene	ENSG00000185085
Ensembl biotype	protein_coding
OMIM	611349
Entrez	80789

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000330574

RefSeq mRNA: 1 — MANE Select: NM_030628 NM_030628

CCDS: CCDS8027

Canonical transcript exons

ENST00000330574 — 2 exons

Exon	Start	End
ENSE00001294811	62646848	62649999
ENSE00001391077	62653170	62653302

Expression profiles

Bgee: expression breadth ubiquitous, 184 present calls, max score 83.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.0044 / max 108.3331, expressed in 1805 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
120182	16.6200	1803
120181	0.3845	158

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	83.31	gold quality
granulocyte	CL:0000094	83.22	gold quality
gastrocnemius	UBERON:0001388	82.90	gold quality
mucosa of transverse colon	UBERON:0004991	82.11	gold quality
islet of Langerhans	UBERON:0000006	81.90	gold quality
muscle of leg	UBERON:0001383	81.76	gold quality
apex of heart	UBERON:0002098	80.76	gold quality
right adrenal gland	UBERON:0001233	80.35	gold quality
skin of leg	UBERON:0001511	80.33	gold quality
right lobe of liver	UBERON:0001114	80.27	gold quality
hindlimb stylopod muscle	UBERON:0004252	80.05	gold quality
right adrenal gland cortex	UBERON:0035827	79.89	gold quality
left adrenal gland	UBERON:0001234	79.84	gold quality
esophagus mucosa	UBERON:0002469	79.78	gold quality
popliteal artery	UBERON:0002250	79.77	gold quality
descending thoracic aorta	UBERON:0002345	79.76	gold quality
tibial artery	UBERON:0007610	79.75	gold quality
left uterine tube	UBERON:0001303	79.68	gold quality
right ovary	UBERON:0002118	79.55	gold quality
body of stomach	UBERON:0001161	79.52	gold quality
skin of abdomen	UBERON:0001416	79.41	gold quality
left adrenal gland cortex	UBERON:0035825	79.41	gold quality
ectocervix	UBERON:0012249	79.37	gold quality
body of uterus	UBERON:0009853	79.36	gold quality
aorta	UBERON:0000947	79.34	gold quality
endocervix	UBERON:0000458	79.32	gold quality
esophagus	UBERON:0001043	79.22	gold quality
thoracic aorta	UBERON:0001515	79.12	gold quality
lower esophagus muscularis layer	UBERON:0035833	79.06	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	79.06	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.29

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

25 targeting INTS5, 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-12136	99.98	72.81	5713
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-542-3P	99.34	67.58	1270
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-5197-3P	98.71	67.05	1905
HSA-MIR-6878-5P	98.49	67.91	2142
HSA-MIR-1233-5P	98.19	66.71	1201
HSA-MIR-6778-5P	98.19	66.59	1239
HSA-MIR-4715-5P	97.62	67.47	506
HSA-MIR-8083	95.93	67.55	694
HSA-MIR-1203	92.38	65.62	48
HSA-MIR-2277-3P	91.94	62.27	299

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.1% of screened cell lines, common-essential.

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ints5	ENSDARG00000077943
mus_musculus	Ints5	ENSMUSG00000071652
rattus_norvegicus	Ints5	ENSRNOG00000026005
drosophila_melanogaster	omd	FBGN0038168
caenorhabditis_elegans		WBGENE00013075

Protein

Protein identifiers

Integrator complex subunit 5 — Q6P9B9 (reviewed: Q6P9B9)

All UniProt accessions (1): Q6P9B9

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.

Subcellular location. Nucleus. Cytoplasm. Nucleus membrane.

Similarity. Belongs to the Integrator subunit 5 family.

RefSeq proteins (1): NP_085131* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029444	INTS5_C	Domain
IPR029445	INTS5_N	Domain
IPR040316	INTS5	Family

Pfam: PF14837, PF14838

UniProt features (92 total): helix 59, strand 13, turn 9, modified residue 3, transmembrane region 3, region of interest 2, initiator methionine 1, chain 1, compositionally biased region 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-Q6P9B9-F1	78.35	0.27

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 (3): 1010, 2, 279

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: 146 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GAANYNYGACNY_UNKNOWN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_RNA_SURVEILLANCE, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GOBP_TRANSCRIPTION_INITIATION_AT_RNA_POLYMERASE_II_PROMOTER, GATA1_04, GCM_NF2, GOBP_SNRNA_PROCESSING, GOBP_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_ELONGATION, GOCC_NUCLEAR_ENVELOPE, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_7, GOCC_INTEGRATOR_COMPLEX, GOCC_NUCLEAR_MEMBRANE, GOBP_DNA_TEMPLATED_TRANSCRIPTION_ELONGATION

GO Biological Process (4): snRNA processing (GO:0016180), regulation of transcription elongation by RNA polymerase II (GO:0034243), snRNA 3’-end processing (GO:0034472), RNA polymerase II transcription initiation surveillance (GO:0160240)

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

GO Cellular Component (8): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020), nuclear membrane (GO:0031965), 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	4
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
transcription initiation at RNA polymerase II promoter	1
nuclear RNA surveillance	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
nucleus	1
nuclear envelope	1
organelle membrane	1
integrator complex	1

Protein interactions and networks

STRING

1304 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
INTS5	INTS7	Q9NVH2	969
INTS5	INTS11	Q5TA45	963
INTS5	INTS8	Q75QN2	938
INTS5	INTS9	Q9NV88	897
INTS5	INTS2	Q9H0H0	874
INTS5	INTS4	Q96HW7	852
INTS5	INTS10	Q9NVR2	832
INTS5	INTS12	Q96CB8	811
INTS5	INTS3	Q68E01	795
INTS5	INTS1	Q8N201	775
INTS5	INTS6	Q9UL03	694
INTS5	INTS13	Q9NVM9	692
INTS5	POLR2A	P24928	608
INTS5	INTS14	Q96SY0	589
INTS5	ZNF507	Q8TCN5	462

IntAct

98 interactions, top by confidence:

A	B	Type	Score
PPP2R1A	STRN	psi-mi:“MI:0914”(association)	0.880
PPP2R1A	STRN	psi-mi:“MI:2364”(proximity)	0.880
INTS5	INTS8	psi-mi:“MI:0915”(physical association)	0.700
INTS5	INTS8	psi-mi:“MI:0407”(direct interaction)	0.700
TOMM22	XRCC3	psi-mi:“MI:0914”(association)	0.640
KRTAP10-8	INTS5	psi-mi:“MI:0915”(physical association)	0.560
LAMP3	METTL15	psi-mi:“MI:0914”(association)	0.530
NPY2R	RTL8C	psi-mi:“MI:0914”(association)	0.530
TMEM171	THAP12	psi-mi:“MI:0914”(association)	0.530
CXCR4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
CD70	METTL15	psi-mi:“MI:0914”(association)	0.530
TNF	B4GALT5	psi-mi:“MI:0914”(association)	0.530
HLA-B	LTN1	psi-mi:“MI:0914”(association)	0.530
PALD1	UNC119B	psi-mi:“MI:0914”(association)	0.530
APLNR	SLC33A1	psi-mi:“MI:0914”(association)	0.530
NPTN	TNPO2	psi-mi:“MI:0914”(association)	0.530
PPP2CA	SMCO3	psi-mi:“MI:0914”(association)	0.420
Ppp2r1a	CCHCR1	psi-mi:“MI:0914”(association)	0.350
CNOT1	IBTK	psi-mi:“MI:0914”(association)	0.350
Cct4	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
SKA3	AP3B1	psi-mi:“MI:0914”(association)	0.350
PPP2CA	DKFZP586J0619	psi-mi:“MI:0914”(association)	0.350
Dennd6a	IFT88	psi-mi:“MI:0914”(association)	0.350

BioGRID (207): INTS5 (Affinity Capture-MS), INTS5 (Affinity Capture-MS), INTS5 (Affinity Capture-MS), INTS5 (Affinity Capture-MS), INTS5 (Affinity Capture-MS), INTS5 (Affinity Capture-MS), INTS5 (Co-fractionation), INTS5 (Co-fractionation), INTS5 (Co-fractionation), INTS5 (Co-fractionation), INTS5 (Affinity Capture-MS), INTS5 (Affinity Capture-MS), INTS5 (Affinity Capture-MS), INTS5 (Affinity Capture-MS), INTS5 (Affinity Capture-MS)

ESM2 similar proteins: A2ARS0, A6NH11, A6QQ91, C9JTQ0, D3ZVB0, D4A929, G3MZC5, O75064, O95996, P16386, P46062, P58660, Q02011, Q08DF2, Q16619, Q29RK8, Q2TBW5, Q2VPB7, Q3TAP4, Q3U0S6, Q3U1Y4, Q562E7, Q5TA50, Q5U651, Q60753, Q63086, Q64375, Q68J42, Q6P9B9, Q6ZS72, Q86YV0, Q8BH02, Q8BQU6, Q8C2K5, Q8CHT3, Q8K0R6, Q8K2B0, Q8N9M5, Q8VD26, Q92791

Diamond homologs: Q6P9B9, Q8CHT3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
INTS5	“form complex”	“Integrator complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 126 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.

GO biological processes:

GO term	Partners	Fold	FDR
RNA polymerase II transcription initiation surveillance	5	43.9×	8e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	124
Likely benign	5
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

202 predictions. Top by Δscore:

Variant	Effect	Δscore
11:62649998:CA:C	acceptor_gain	1.0000
11:62650000:C:CC	acceptor_gain	1.0000
11:62649995:GAGCA:G	acceptor_gain	0.9900
11:62649996:AGCA:A	acceptor_gain	0.9900
11:62649997:GCA:G	acceptor_gain	0.9900
11:62649998:CAC:C	acceptor_gain	0.9900
11:62649999:AC:A	acceptor_loss	0.9900
11:62650000:C:CA	acceptor_loss	0.9900
11:62650004:A:T	acceptor_gain	0.9900
11:62649997:GCACT:G	acceptor_gain	0.9800
11:62649999:ACTAC:A	acceptor_gain	0.9800
11:62650003:C:CT	acceptor_gain	0.9800
11:62653166:CTACC:C	donor_loss	0.9800
11:62653167:TAC:T	donor_loss	0.9800
11:62653168:ACC:A	donor_loss	0.9800
11:62653169:CCT:C	donor_loss	0.9800
11:62649996:AGCAC:A	acceptor_gain	0.9700
11:62649998:CACT:C	acceptor_gain	0.9700
11:62650000:CTAC:C	acceptor_gain	0.9700
11:62652684:ATCG:A	donor_gain	0.9700
11:62653165:ACTAC:A	donor_loss	0.9700
11:62650001:T:G	acceptor_gain	0.9600
11:62650000:CTACA:C	acceptor_gain	0.9500
11:62650001:T:A	acceptor_gain	0.9300
11:62653102:C:CT	donor_gain	0.9300
11:62653103:T:TT	donor_gain	0.9300
11:62650877:TTTTA:T	donor_gain	0.9100
11:62650011:C:CT	acceptor_gain	0.9000
11:62649994:TGA:T	acceptor_gain	0.8700
11:62649995:GAG:G	acceptor_gain	0.8700

AlphaMissense

6433 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:62648743:A:G	L446P	1.000
11:62649049:A:G	L344P	1.000
11:62649058:A:G	L341P	1.000
11:62649060:G:C	F340L	1.000
11:62649060:G:T	F340L	1.000
11:62649062:A:G	F340L	1.000
11:62649142:A:G	L313P	1.000
11:62649178:A:G	L301P	1.000
11:62649187:A:G	L298P	1.000
11:62649190:A:C	I297S	1.000
11:62649190:A:G	I297T	1.000
11:62649190:A:T	I297N	1.000
11:62649199:A:T	V294D	1.000
11:62649343:C:T	G246D	1.000
11:62649352:A:G	L243P	1.000
11:62649352:A:T	L243H	1.000
11:62649355:A:T	V242D	1.000
11:62649367:A:C	I238S	1.000
11:62649367:A:T	I238N	1.000
11:62649378:A:C	F234L	1.000
11:62649378:A:T	F234L	1.000
11:62649380:A:G	F234L	1.000
11:62649388:C:T	G231D	1.000
11:62649389:C:G	G231R	1.000
11:62649391:A:T	I230N	1.000
11:62649403:A:T	V226D	1.000
11:62649405:C:A	W225C	1.000
11:62649405:C:G	W225C	1.000
11:62649406:C:G	W225S	1.000
11:62649407:A:G	W225R	1.000

dbSNP variants (sampled 300 via entrez): RS1000024694 (11:62653844 G>A,C), RS1000067995 (11:62651445 A>AT), RS1000121409 (11:62651128 C>G), RS1000824171 (11:62649076 T>A), RS1001084191 (11:62649782 G>A,C), RS1001326727 (11:62654807 A>G,T), RS1001536737 (11:62649502 T>C), RS1001759069 (11:62650347 A>C), RS1001990897 (11:62649776 G>A), RS1002404404 (11:62655168 C>A), RS1002459803 (11:62654883 C>T), RS1002894238 (11:62651600 A>G), RS1003399657 (11:62651361 C>T), RS1003469983 (11:62653645 T>A), RS1004541857 (11:62650306 T>C)

Disease associations

OMIM: gene MIM:611349 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST005956_12	Waist-to-hip ratio adjusted for BMI	2.000000e-06
GCST005956_2	Waist-to-hip ratio adjusted for BMI	1.000000e-08
GCST005962_37	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	5.000000e-07
GCST005962_51	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	1.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
GSK-J4	decreases expression	1
FR900359	decreases phosphorylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
ferrous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
(+)-JQ1 compound	increases expression	1
MT19c compound	decreases expression	1
Leflunomide	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases expression	1
Catechin	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Vincristine	decreases expression	1
Cyclosporine	decreases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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