INTS8
Chr 8ARintegrator complex subunit 8
Also known as: C8orf52, INT8, NEDCHS
The INTS8 protein is a component of the integrator complex that terminates RNA polymerase II transcription and processes small nuclear RNAs, serving as a quality checkpoint during transcription elongation. Mutations cause an autosomal recessive neurodevelopmental disorder with cerebellar hypoplasia and spasticity. The gene is highly constrained against loss-of-function variants (pLI 0.94, LOEUF 0.31), indicating that functional copies are essential for normal development.
Primary Disease Associations & Inheritance
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
223 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 1 | 38 | 0 | 39 |
Likely Pathogenic | 0 | 0 | 3 | 0 | 3 |
VUS | 2 | 99 | 1 | 0 | 102 |
Likely Benign | 0 | 7 | 0 | 7 | 14 |
Benign | 0 | 0 | 5 | 3 | 8 |
| Total | 2 | 107 | 47 | 10 | 166 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
INTS8 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools