INTS15

Chr 7

integrator complex subunit 15

NCBI Gene: 79034 ENSG00000146576 UniProt: Q96N11 OMIM: 621239

The protein is a component of the integrator complex that terminates RNA polymerase II transcription and processes non-coding RNAs, serving as a bridge between different integrator modules and helping recruit transcription factors at promoters. Mutations cause autosomal dominant neurodevelopmental disorder with developmental delay, intellectual disability, and behavioral abnormalities. The gene is highly constrained against loss-of-function variants (pLI 0.98, LOEUF 0.30), indicating that even single functional copies are critical for normal development.

OMIM ResearchSummary from RefSeq, UniProt

Component of the integrator complex, a multiprotein complex that terminates RNA polymerase II (Pol II) transcription in the promoter-proximal region of genes (PubMed:36920904, PubMed:38570683, PubMed:38823386). 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 (PubMed:38570683). 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) (PubMed:38570683). INTS15 is part of the integrator tail module that acts as a platform for the recruitment of transcription factors at promoters (PubMed:38823386). Within the integrator complex, INTS15 is required to bridge different integrator modules (PubMed:36920904)

OMIM ResearchGenerating clinical summary…

LOEUF 0.30

Clinical Summary— INTS15

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.

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