INTS6

Chr 13AD

integrator complex subunit 6

Also known as: DBI-1, DDX26, DDX26A, DICE1, HDB, INT6, MRD78, Notchl2

NCBI Gene: 26512 ENSG00000102786 UniProt: Q9UL03 OMIM: 604331

INTS6 encodes a component of the integrator complex that regulates RNA polymerase II transcription termination and processes small nuclear RNAs, acting as a molecular adapter to recruit protein phosphatase 2A to transcription checkpoints. Mutations cause autosomal dominant developmental delay with variable intellectual disability and behavioral abnormalities, typically presenting in early childhood. This gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely incompatible with normal development.

OMIM ResearchSummary from RefSeq, UniProt

DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. The protein encoded by this gene is a DEAD box protein that is part of a complex that interacts with the C-terminus of RNA polymerase II and is involved in 3' end processing of snRNAs. In addition, this gene is a candidate tumor suppressor and is located in the critical region of loss of heterozygosity (LOH). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2015]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal dominant 78MIM #621627

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.14

LOEUF· LoF intol.

LOF

Mechanism· predicted