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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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INTS9
integrator complex subunit 9
Chromosome 8 · 8p21.1
NCBI Gene: 55756Ensembl: ENSG00000104299.16HGNC: HGNC:25592UniProt: Q9NV88
65PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingsnRNA processingnegative regulation of transforming growth factor beta receptor signaling pathwayregulation of transcription elongation by RNA polymerase IIneurodegenerative diseaseovarian neoplasmliver diseaseskin disease
✦AI Summary

INTS9 is a core component of the Integrator complex, a multiprotein assembly that regulates RNA polymerase II (Pol II) transcription termination and non-coding RNA processing 1. As part of the catalytic INTS4-INTS9-INTS11 cleavage module, INTS9 facilitates three mechanisms of transcription control: dephosphorylation of Pol II's C-terminal domain, endonucleolytic degradation of nascent transcripts, and Pol II release from DNA 2. INTS9 interacts stably with INTS11 through conserved C-terminal domains essential for snRNA 3'-end processing and controls expression of non-coding RNAs including enhancer RNAs, snRNAs, and lncRNAs 2. INTS9 forms a functional trimeric complex with INTS11 and BRAT1, a cytoplasmic chaperone that stabilizes and facilitates nuclear import of the endonuclease module 3. Assembly of the mature INTS9-containing cleavage module requires inositol hexaphosphate (IP6) as an essential cofactor, with BRAT1 and WDR73 serving as critical biogenesis factors 1. Clinically, mutations disrupting INTS9 interactions with BRAT1 or INTS11 impair Integrator function and cause neurodevelopmental and neurodegenerative disorders characterized by defects in RNA processing, neuronal differentiation, and REST-responsive gene activation 456.

Sources cited
1
INTS9 is part of the RNA cleavage module; BRAT1 and WDR73 are critical biogenesis factors; IP6 is essential cofactor for cleavage module maturation
PMID: 39032489
2
INTS9-INTS11 interaction through C-terminal domains is crucial for snRNA 3'-end processing; structural basis of complex formation
PMID: 28396433
3
BRAT1 stabilizes INTS11 in cytoplasm and is required for Integrator nuclear function; structures reveal BRAT1 C-terminus captured in INTS11 active site
PMID: 39032490
4
BRAT1 interacts with INTS9/INTS11; BRAT1 deletion impairs 3' end processing of usnRNAs and snoRNAs; defects found in patient-derived neurological disease cells
PMID: 36028512
5
INTS9 and INTS11 form trimeric complex with BRAT1 for neuronal differentiation; mutations in BRAT1 diminish association with INTS11/INTS9; defects linked to neurodevelopmental disorders
PMID: 38805275
6
INTS11 and INTS9 interact with BRAT1 forming trimeric complex; BRAT1 depletion disrupts neural differentiation; disease-causing BRAT1 mutations diminish INTS11/INTS9 association
PMID: 37609215
7
INTS4 associates specifically with INTS9/11 to form cleavage module; INTS4/9/11 critical for UsnRNA biogenesis
PMID: 29471365
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.27Weak
ovarian neoplasmOpen Targets
0.27Weak
liver diseaseOpen Targets
0.23Weak
skin diseaseOpen Targets
0.11Weak
localized superficial swelling, mass, or lumpOpen Targets
0.11Weak
neoplasmOpen Targets
0.08Suggestive
HypercholesterolemiaOpen Targets
0.07Suggestive
phototoxic dermatitisOpen Targets
0.07Suggestive
Hemoglobin E - beta-thalassemiaOpen Targets
0.06Suggestive
hemoglobin E-beta-thalassemia syndromeOpen Targets
0.06Suggestive
intestinal obstructionOpen Targets
0.05Suggestive
hemoglobin D diseaseOpen Targets
0.05Suggestive
Adult-onset autosomal recessive sideroblastic anemiaOpen Targets
0.05Suggestive
astrocytomaOpen Targets
0.05Suggestive
gluthathione peroxidase deficiencyOpen Targets
0.05Suggestive
hemolytic anemia due to erythrocyte adenosine deaminase overproductionOpen Targets
0.04Suggestive
IRIDA syndromeOpen Targets
0.04Suggestive
dominant beta-thalassemiaOpen Targets
0.04Suggestive
gliomaOpen Targets
0.04Suggestive
delta-beta-thalassemiaOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
POLR2BProtein interaction100%POLR2LProtein interaction100%POLR2KProtein interaction100%POLR2EProtein interaction100%POLR2DProtein interaction100%POLR2HProtein interaction100%
Tissue Expression6 tissues
Lung
100%
Ovary
82%
Heart
81%
Brain
68%
Bone Marrow
63%
Liver
48%
Gene Interaction Network
Click a node to explore
INTS9POLR2BPOLR2LPOLR2KPOLR2EPOLR2DPOLR2H
PROTEIN STRUCTURE
Preparing viewer…
PDB5V8W · 2.10 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.87LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.68 [0.53–0.87]
RankingsWhere INTS9 stands among ~20K protein-coding genes
  • #7,176of 20,598
    Most Researched65
  • #7,682of 17,882
    Most Constrained (LOEUF)0.87
Genes detectedINTS9
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Assembly mechanism of Integrator's RNA cleavage module.
PMID: 39032489
Mol Cell · 2024
1.00
2
BRAT1 links Integrator and defective RNA processing with neurodegeneration.
PMID: 36028512
Nat Commun · 2022
0.90
3
Neuronal differentiation requires BRAT1 complex to remove REST from chromatin.
PMID: 38805275
Proc Natl Acad Sci U S A · 2024
0.80
4
Inositol hexakisphosphate is required for Integrator function.
PMID: 36180473
Nat Commun · 2022
0.70
5
Molecular basis for the interaction between Integrator subunits IntS9 and IntS11 and its functional importance.
PMID: 28396433
Proc Natl Acad Sci U S A · 2017
0.60