INTS14

Summary

INTS14 (integrator complex subunit 14, HGNC:25372) is a protein-coding gene on chromosome 15q22.31, encoding Integrator complex subunit 14 (Q96SY0). 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: 57.4% of cell lines).

Predicted to be involved in snRNA 3’-end processing. Located in cytoplasm. Part of integrator complex. Is active in nucleus.

Source: NCBI Gene 81556 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 73 total
• Cancer dependency (DepMap): dependent in 57.4% of screened cell lines
• MANE Select transcript: NM_001394796

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25372
Approved symbol	INTS14
Name	integrator complex subunit 14
Location	15q22.31
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP564O1664
Ensembl gene	ENSG00000138614
Ensembl biotype	protein_coding
OMIM	620878
Entrez	81556

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 23 protein_coding, 4 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000313182, ENST00000420799, ENST00000431261, ENST00000442903, ENST00000561769, ENST00000562830, ENST00000563729, ENST00000564306, ENST00000567744, ENST00000567923, ENST00000567940, ENST00000568573, ENST00000569004, ENST00000569180, ENST00000569491, ENST00000569565, ENST00000573314, ENST00000652388, ENST00000888482, ENST00000888483, ENST00000888484, ENST00000888485, ENST00000888486, ENST00000888487, ENST00000920146, ENST00000920147, ENST00000920148, ENST00000920149, ENST00000957101, ENST00000957102

RefSeq mRNA: 10 — MANE Select: NM_001394796 NM_001136043, NM_001207058, NM_001207059, NM_001366360, NM_001366364, NM_001366365, NM_001394794, NM_001394795, NM_001394796, NM_001394797

CCDS: CCDS10211, CCDS45283, CCDS92020, CCDS92021, CCDS92022

Canonical transcript exons

ENST00000313182 — 12 exons

Exon	Start	End
ENSE00001270621	65611098	65611131
ENSE00001327120	65578757	65579659
ENSE00003481505	65591598	65591731
ENSE00003487902	65599774	65599929
ENSE00003523771	65584770	65584888
ENSE00003526524	65607159	65607442
ENSE00003542831	65605129	65605236
ENSE00003563300	65593428	65593572
ENSE00003581674	65598321	65598463
ENSE00003657785	65598872	65598990
ENSE00003659277	65581954	65582019
ENSE00003660445	65595733	65595825

Expression profiles

Bgee: expression breadth ubiquitous, 232 present calls, max score 91.64.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.1453 / max 162.6621, expressed in 1802 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
150557	11.9493	1787
150558	5.9978	1734
150559	1.1982	897

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
rectum	UBERON:0001052	91.64	gold quality
ventricular zone	UBERON:0003053	91.36	gold quality
islet of Langerhans	UBERON:0000006	91.10	gold quality
body of pancreas	UBERON:0001150	90.51	gold quality
right uterine tube	UBERON:0001302	90.49	gold quality
calcaneal tendon	UBERON:0003701	90.13	gold quality
right lobe of thyroid gland	UBERON:0001119	89.98	gold quality
gall bladder	UBERON:0002110	89.73	gold quality
left lobe of thyroid gland	UBERON:0001120	89.70	gold quality
pancreas	UBERON:0001264	89.54	gold quality
adrenal tissue	UBERON:0018303	89.51	gold quality
skin of abdomen	UBERON:0001416	89.31	gold quality
right ovary	UBERON:0002118	89.14	gold quality
skin of leg	UBERON:0001511	88.89	gold quality
granulocyte	CL:0000094	88.86	gold quality
small intestine Peyer’s patch	UBERON:0003454	88.85	gold quality
right adrenal gland cortex	UBERON:0035827	88.83	gold quality
right adrenal gland	UBERON:0001233	88.82	gold quality
left ovary	UBERON:0002119	88.73	gold quality
left uterine tube	UBERON:0001303	88.65	gold quality
adenohypophysis	UBERON:0002196	88.63	gold quality
left adrenal gland	UBERON:0001234	88.58	gold quality
ganglionic eminence	UBERON:0004023	88.52	gold quality
thyroid gland	UBERON:0002046	88.51	gold quality
mucosa of stomach	UBERON:0001199	88.42	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.39	gold quality
body of stomach	UBERON:0001161	88.38	gold quality
mucosa of transverse colon	UBERON:0004991	88.37	gold quality
transverse colon	UBERON:0001157	88.34	gold quality
minor salivary gland	UBERON:0001830	88.33	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.99

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 57.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• INTS10-INTS13-INTS14 form a functional module of Integrator that binds nucleic acids and the cleavage module. (PMID:32647223)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ints14	ENSDARG00000041429
mus_musculus	Ints14	ENSMUSG00000034263
rattus_norvegicus	Ints14	ENSRNOG00000012469
drosophila_melanogaster	IntS14	FBGN0031314

Protein

Protein identifiers

Integrator complex subunit 14 — Q96SY0 (reviewed: Q96SY0)

Alternative names: von Willebrand factor A domain-containing protein 9

All UniProt accessions (10): Q96SY0, B4DJL6, B4DVT3, H3BMK7, H3BN95, H3BNR6, H3BP17, H3BRY6, H3BT02, H3BV25

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, INTS14 is part of the integrator tail module that acts as a platform for the recruitment of transcription factors at promoters.

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

Subcellular location. Nucleus.

Tissue specificity. Strongly expressed in numerous cancer cells compared with their non-cancerous counterparts (lung, prostate, colon, stomach and skin).

Similarity. Belongs to the Integrator subunit 14 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q96SY0-1	1	yes
Q96SY0-2	2
Q96SY0-4	4
Q96SY0-3	3

RefSeq proteins (10): NP_001129515, NP_001193987, NP_001193988, NP_001353289, NP_001353293, NP_001353294, NP_001381723, NP_001381724, NP_001381725, NP_001381726 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002035	VWF_A	Domain
IPR036465	vWFA_dom_sf	Homologous_superfamily
IPR039841	INTS14	Family
IPR045814	IntS14_b-barrel	Domain
IPR046471	IntS14_C	Domain

Pfam: PF13519, PF19435, PF20504

UniProt features (66 total): strand 25, helix 19, turn 6, sequence conflict 4, splice variant 4, binding site 3, mutagenesis site 2, chain 1, domain 1, modified residue 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
8PK5	X-RAY DIFFRACTION	2.5
6SN1	X-RAY DIFFRACTION	2.54
8RC4	ELECTRON MICROSCOPY	3.1
9EOC	ELECTRON MICROSCOPY	3.3
8RBZ	ELECTRON MICROSCOPY	3.7
9EP1	ELECTRON MICROSCOPY	4
9FA4	ELECTRON MICROSCOPY	4
9FA7	ELECTRON MICROSCOPY	4
8RBX	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96SY0-F1	86.44	0.62

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 (3): 10; 12; 86

Post-translational modifications (1): 418

Mutagenesis-validated functional residues (2):

Position	Phenotype
8–12	abolished interaction with ints10.
11–15	abolished interaction with ints10.

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): GSE45365_NK_CELL_VS_CD11B_DC_UP, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_RNA_SURVEILLANCE, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GOBP_TRANSCRIPTION_INITIATION_AT_RNA_POLYMERASE_II_PROMOTER, GOBP_SNRNA_PROCESSING, GOBP_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_ELONGATION, GOCC_INTEGRATOR_COMPLEX, GOBP_DNA_TEMPLATED_TRANSCRIPTION_ELONGATION, chr15q22, REACTOME_RNA_POLYMERASE_II_TRANSCRIBES_SNRNA_GENES, STK33_SKM_DN, GOBP_SNRNA_METABOLIC_PROCESS, CBX5_TARGET_GENES, DIDO1_TARGET_GENES

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 (2): metal ion binding (GO:0046872), protein binding (GO:0005515)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), integrator complex (GO:0032039), INTAC complex (GO:0160232), cytoplasm (GO:0005737), membrane (GO:0016020)

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
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
cation binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
integrator complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1832 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
INTS14	INTS13	Q9NVM9	955
INTS14	INTS1	Q8N201	843
INTS14	INTS10	Q9NVR2	772
INTS14	INTS6L	Q5JSJ4	709
INTS14	INTS11	Q5TA45	675
INTS14	INTS15	Q96N11	668
INTS14	INTS12	Q96CB8	667
INTS14	INTS9	Q9NV88	657
INTS14	INTS4	Q96HW7	640
INTS14	INTS5	Q6P9B9	589
INTS14	INTS3	Q68E01	585
INTS14	INTS8	Q75QN2	571
INTS14	INTS6	Q9UL03	556
INTS14	INTS7	Q9NVH2	555
INTS14	HACD3	Q9P035	513

IntAct

84 interactions, top by confidence:

A	B	Type	Score
INTS10	INTS14	psi-mi:“MI:0915”(physical association)	0.900
INTS14	INTS10	psi-mi:“MI:0915”(physical association)	0.900
INTS11	INTS4	psi-mi:“MI:0915”(physical association)	0.860
INTS13	INTS14	psi-mi:“MI:0915”(physical association)	0.810
INTS14	INTS13	psi-mi:“MI:0915”(physical association)	0.810
INTS13	INTS14	psi-mi:“MI:0407”(direct interaction)	0.810
INTS13	INTS14	psi-mi:“MI:0914”(association)	0.810
INTS14	INTS13	psi-mi:“MI:0914”(association)	0.810
INTS10	INTS11	psi-mi:“MI:0915”(physical association)	0.740
INTS13	INTS11	psi-mi:“MI:0915”(physical association)	0.690
INTS13	INTS11	psi-mi:“MI:0914”(association)	0.690
BCL7C	ARID1A	psi-mi:“MI:0914”(association)	0.640
KPNA1	TCERG1	psi-mi:“MI:0914”(association)	0.640
INTS10	PGK2	psi-mi:“MI:0914”(association)	0.530
SUPT5H	POLR2D	psi-mi:“MI:0914”(association)	0.530
TRPC4AP	SMCHD1	psi-mi:“MI:0914”(association)	0.530

BioGRID (131): VWA9 (Affinity Capture-MS), VWA9 (Affinity Capture-MS), VWA9 (Affinity Capture-MS), VWA9 (Affinity Capture-MS), VWA9 (Affinity Capture-MS), VWA9 (Affinity Capture-MS), VWA9 (Affinity Capture-MS), VWA9 (Co-fractionation), GOLGA4 (Affinity Capture-MS), MCM5 (Affinity Capture-MS), MAP3K4 (Affinity Capture-MS), POLR2A (Affinity Capture-MS), PPL (Affinity Capture-MS), PPP2R1A (Affinity Capture-MS), TNFRSF1A (Affinity Capture-MS)

ESM2 similar proteins: A4D1B5, A5PKN5, A7RV13, D3IUT5, O70167, O70173, O75747, P42695, Q12769, Q28HN9, Q3MHH2, Q3TCV3, Q3UPC7, Q3URV1, Q5BKL1, Q5EA76, Q5R8P3, Q5RB52, Q5RC62, Q5RD58, Q5SUD9, Q5ZK21, Q5ZL79, Q63517, Q66H58, Q66HC3, Q66KD9, Q6DFW0, Q6GN08, Q6ZQK0, Q6ZW61, Q8BJW5, Q8BKN5, Q8IV33, Q8K1K4, Q8N957, Q8NB91, Q8R3P6, Q8TAM1, Q91YN0

Diamond homologs: Q5EA76, Q5ZK21, Q66H58, Q66KD9, Q8R3P6, Q96SY0, Q9VPY0

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
INTS14	“form complex”	“Integrator complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 79 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	5	66.8×	4e-07
Signaling by FGFR2 IIIa TM	5	52.7×	1e-06
Abortive elongation of HIV-1 transcript in the absence of Tat	6	52.3×	2e-07
RNA Pol II CTD phosphorylation and interaction with CE during HIV infection	6	42.9×	4e-07
RNA Pol II CTD phosphorylation and interaction with CE	6	42.9×	4e-07
mRNA Capping	6	40.1×	4e-07
MicroRNA (miRNA) biogenesis	5	40.1×	3e-06
Pausing and recovery of Tat-mediated HIV elongation	6	38.8×	4e-07

GO biological processes:

GO term	Partners	Fold	FDR
RNA polymerase II transcription initiation surveillance	5	60.8×	6e-06
regulation of transcription elongation by RNA polymerase II	5	55.0×	6e-06
regulation of G1/S transition of mitotic cell cycle	5	21.0×	3e-04
chromatin remodeling	7	7.0×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	58
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2028 predictions. Top by Δscore:

Variant	Effect	Δscore
15:65579657:CTC:C	acceptor_gain	1.0000
15:65579658:TC:T	acceptor_gain	1.0000
15:65579659:CC:C	acceptor_gain	1.0000
15:65579659:CCT:C	acceptor_loss	1.0000
15:65579660:CTG:C	acceptor_loss	1.0000
15:65580839:A:C	donor_gain	1.0000
15:65581949:CTCAC:C	donor_loss	1.0000
15:65581950:TCA:T	donor_loss	1.0000
15:65581951:CA:C	donor_loss	1.0000
15:65581952:A:C	donor_loss	1.0000
15:65582016:CTGT:C	acceptor_gain	1.0000
15:65582017:TGT:T	acceptor_gain	1.0000
15:65582018:GT:G	acceptor_gain	1.0000
15:65582018:GTCT:G	acceptor_loss	1.0000
15:65582020:C:CC	acceptor_gain	1.0000
15:65582023:T:C	acceptor_gain	1.0000
15:65582023:T:TC	acceptor_gain	1.0000
15:65582029:G:C	acceptor_gain	1.0000
15:65582029:G:GC	acceptor_gain	1.0000
15:65584765:GTTA:G	donor_loss	1.0000
15:65584768:A:AT	donor_loss	1.0000
15:65584769:C:A	donor_loss	1.0000
15:65584886:CAT:C	acceptor_gain	1.0000
15:65584886:CATCT:C	acceptor_gain	1.0000
15:65584887:ATC:A	acceptor_loss	1.0000
15:65584888:TC:T	acceptor_loss	1.0000
15:65584889:C:A	acceptor_loss	1.0000
15:65584889:C:CC	acceptor_gain	1.0000
15:65584890:T:C	acceptor_gain	1.0000
15:65584890:T:TC	acceptor_gain	1.0000

AlphaMissense

3417 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:65579508:A:G	L486P	1.000
15:65579520:G:T	A482D	1.000
15:65579529:A:G	L479P	1.000
15:65579586:A:G	L460P	1.000
15:65579634:G:T	A444D	1.000
15:65579643:C:G	R441P	1.000
15:65579649:C:G	R439P	1.000
15:65579650:G:T	R439S	1.000
15:65579655:A:G	L437P	1.000
15:65579659:C:T	E436K	1.000
15:65581973:T:A	K429I	1.000
15:65581974:T:C	K429E	1.000
15:65581982:A:G	L426P	1.000
15:65581986:T:C	K425E	1.000
15:65581987:C:A	R424S	1.000
15:65581987:C:G	R424S	1.000
15:65581988:C:A	R424M	1.000
15:65581988:C:G	R424T	1.000
15:65581991:G:T	A423E	1.000
15:65581992:C:G	A423P	1.000
15:65581996:T:A	R421S	1.000
15:65581996:T:G	R421S	1.000
15:65581997:C:A	R421I	1.000
15:65581997:C:G	R421T	1.000
15:65582005:C:A	K418N	1.000
15:65582005:C:G	K418N	1.000
15:65582007:T:C	K418E	1.000
15:65582007:T:G	K418Q	1.000
15:65582015:T:A	D415V	1.000
15:65582016:C:G	D415H	1.000

dbSNP variants (sampled 300 via entrez): RS1000033434 (15:65584256 T>TG), RS1000090751 (15:65588539 G>C), RS1000169288 (15:65603520 A>C), RS1000256554 (15:65590978 C>T), RS1000270552 (15:65596430 A>G), RS1000304699 (15:65609984 T>A), RS1000388149 (15:65610530 G>A), RS1000619051 (15:65610114 C>T), RS1000840520 (15:65604948 A>G), RS1000855608 (15:65603296 T>A,C), RS1000860968 (15:65582822 T>C), RS1000876205 (15:65611370 G>C), RS1000953117 (15:65579972 AAGG>A), RS1001032311 (15:65597895 A>ATTAT), RS1001149628 (15:65590467 C>T)

Disease associations

OMIM: gene MIM:620878 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST000587_7	Mean corpuscular hemoglobin	3.000000e-09
GCST004006_13	Mean corpuscular hemoglobin	3.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004509	hemoglobin measurement
EFO:0004527	mean corpuscular hemoglobin

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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
Air Pollutants	affects cotreatment, increases abundance, increases expression, increases oxidation, decreases expression	2
triphenyl phosphate	affects expression	1
alpha-pinene	increases expression, increases oxidation, increases abundance, affects cotreatment	1
sodium arsenite	decreases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Acrolein	increases oxidation, increases abundance, affects cotreatment, increases expression	1
Arsenic	affects methylation	1
Atrazine	decreases expression	1
Coal	decreases expression, increases abundance	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Folic Acid	affects expression	1
Gallic Acid	decreases expression	1
Ivermectin	decreases expression	1
Lead	affects expression	1
Oxygen	decreases expression	1
Ozone	affects cotreatment, increases expression, increases oxidation, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1
Smoke	decreases expression, increases abundance	1
Thimerosal	increases expression	1
Tretinoin	decreases expression	1
Valproic Acid	affects expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1
Volatile Organic Compounds	increases expression, increases oxidation, affects cotreatment	1

Clinical trials (associated diseases)

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