INTS10

Chr 8

integrator complex subunit 10

Also known as: C8orf35, INT10

INTS10 encodes a component of the Integrator complex that regulates RNA polymerase II transcription termination and processes small nuclear RNAs. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability and developmental delay. The gene is highly constrained against loss-of-function mutations (pLI 0.999985927609912), indicating it is essential for normal cellular function.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
4
Pubs (1 yr)
79
P/LP submissions
0%
P/LP missense
0.16
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryINTS10
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
79 unique Pathogenic / Likely Pathogenic· 95 VUS of 208 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.16LOEUF
pLI 1.000
Z-score 5.59
OE 0.05 (0.020.16)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.44Z-score
OE missense 0.79 (0.720.87)
312 obs / 392.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.05 (0.020.16)
00.351.4
Missense OE0.79 (0.720.87)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 2 / 40.2Missense obs/exp: 312 / 392.5Syn Z: -0.31
DN
0.3495th %ile
GOF
0.3888th %ile
LOF
0.71top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.16

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

208 submitted variants in ClinVar

Classification Summary

Pathogenic76
Likely Pathogenic3
VUS95
Likely Benign3
76
Pathogenic
3
Likely Pathogenic
95
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
76
0
76
Likely Pathogenic
0
0
3
0
3
VUS
0
86
9
0
95
Likely Benign
0
1
2
0
3
Benign
0
0
0
0
0
Total087900177

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

INTS10 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗