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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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INTS4
integrator complex subunit 4
Chromosome 11 · 11q14.1
NCBI Gene: 92105Ensembl: ENSG00000149262.19HGNC: HGNC:25048UniProt: A0A8C8UVZ7
66PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
INTAC complexprotein-macromolecule adaptor activitysnRNA processingregulation of transcription elongation by RNA polymerase IIsystemic lupus erythematosusceliac diseaseprostate carcinomapreeclampsia
✦AI Summary

INTS4 (integrator complex subunit 4) is a scaffolding component of the Integrator complex, a multiprotein assembly essential for transcriptional regulation and RNA processing. INTS4 functions as a helical repeat protein that stabilizes the catalytic core of Integrator by linking INTS9 and INTS11 through multiple interdependent interfaces 1, forming a ternary complex responsible for endonucleolytic activity 2. The Integrator complex terminates RNA polymerase II transcription in promoter-proximal regions through three mechanisms: dephosphorylating Pol II's C-terminal domain, degrading nascent RNA via endonuclease activity, and promoting Pol II release from DNA [UniProt citations]. INTS4 is critical for 3'-end processing of non-coding RNAs including snRNAs, enhancer RNAs, and lncRNAs 2. Additionally, proper INTS4 function requires inositol hexakisphosphate (IP6) as a cofactor that stabilizes the cleavage module conformation; assembly defects involving INTS4 are associated with neurodevelopmental disorders 3. INTS4 depletion impairs snRNA maturation and disrupts Cajal body integrity, demonstrating its importance for nuclear body homeostasis 4. Functionally, INTS4 interacts with proteins regulating neuroplasticity and apoptosis 5, suggesting roles beyond transcriptional regulation. Recent immunoproteomic studies identified INTS4 as an immunogenic antigen in MEN1-related neuroendocrine tumors 6, indicating potential clinical significance.

Sources cited
1
INTS4 is a Symplekin-like scaffold that specifically binds INTS9/11 to form the Integrator cleavage module with catalytic function for snRNA and enhancer RNA 3'-end processing
PMID: 29471365
2
INTS4 is a helical repeat protein that stabilizes nuclease domains and other Integrator components in the catalytic core structure determined by cryo-EM
PMID: 33548203
3
INTS4 assembly into the cleavage module is regulated by BRAT1 and WDR73; IP6 is required for mature cleavage module conformation and neurodevelopmental disorders result from defects in this assembly process
PMID: 39032489
4
INTS4 depletion abrogates snRNA 3'-end processing and causes loss of Cajal body integrity with accumulation of coilin in nucleoli
PMID: 22250197
5
INTS4 interacts with KIBRA and HAX-1, which are involved in neuroplasticity, apoptosis, and cytoskeletal regulation
PMID: 17010949
6
INTS4 was identified as an immunogenic antigen in plasma of MEN1 patients with duodenopancreatic neuroendocrine tumors with high binding affinity for MHC-II
PMID: 41562477
Disease Associationsⓘ20
systemic lupus erythematosusOpen Targets
0.33Weak
celiac diseaseOpen Targets
0.27Weak
prostate carcinomaOpen Targets
0.26Weak
preeclampsiaOpen Targets
0.26Weak
hepatocellular carcinomaOpen Targets
0.07Suggestive
neoplasmOpen Targets
0.04Suggestive
liver diseaseOpen Targets
0.02Suggestive
pulmonary tuberculosisOpen Targets
0.02Suggestive
Townes-Brocks syndromeOpen Targets
0.01Suggestive
rheumatoid arthritisOpen Targets
0.01Suggestive
myeloid sarcomaOpen Targets
0.01Suggestive
tuberculosisOpen Targets
0.01Suggestive
cancerOpen Targets
0.01Suggestive
type 1 diabetes mellitusOpen Targets
0.00Suggestive
breast cancerOpen Targets
0.00Suggestive
breast neoplasmOpen Targets
0.00Suggestive
liver cancerOpen Targets
0.00Suggestive
lung adenocarcinomaOpen Targets
0.00Suggestive
melanomaOpen Targets
0.00Suggestive
posterior cortical atrophyOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
INTS15Shared pathway100%POLR2BProtein interaction100%POLR2LProtein interaction100%POLR2KProtein interaction100%POLR2EProtein interaction100%POLR2DProtein interaction100%
Tissue Expression6 tissues
Ovary
100%
Bone Marrow
97%
Liver
85%
Lung
85%
Brain
80%
Heart
63%
Gene Interaction Network
Click a node to explore
INTS4INTS15POLR2BPOLR2LPOLR2KPOLR2EPOLR2D
PROTEIN STRUCTURE
Preparing viewer…
PDB8RC4 · 3.10 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.73LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.57 [0.44–0.73]
RankingsWhere INTS4 stands among ~20K protein-coding genes
  • #7,077of 20,598
    Most Researched66
  • #5,689of 17,882
    Most Constrained (LOEUF)0.73
Genes detectedINTS4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Assembly mechanism of Integrator's RNA cleavage module.
PMID: 39032489
Mol Cell · 2024
1.00
2
Inositol hexakisphosphate is required for Integrator function.
PMID: 36180473
Nat Commun · 2022
0.90
3
Integrator subunit 4 is a 'Symplekin-like' scaffold that associates with INTS9/11 to form the Integrator cleavage module.
PMID: 29471365
Nucleic Acids Res · 2018
0.80
4
Structure of the catalytic core of the Integrator complex.
PMID: 33548203
Mol Cell · 2021
0.70
5
The integrator complex is required for integrity of Cajal bodies.
PMID: 22250197
J Cell Sci · 2012
0.60