INTS10

Chr 8

integrator complex subunit 10

Also known as: C8orf35, INT10

NCBI Gene: 55174 ENSG00000104613 UniProt: Q9NVR2

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.

ResearchSummary from RefSeq, UniProt

INTS10 is a subunit of the Integrator complex, which associates with the C-terminal domain of RNA polymerase II large subunit (POLR2A; MIM 180660) and mediates 3-prime end processing of small nuclear RNAs U1 (RNU1; MIM 180680) and U2 (RNU2; MIM 180690) (Baillat et al., 2005 [PubMed 16239144]).[supplied by OMIM, Mar 2008]

ResearchGenerating clinical summary…

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)

—

P/LP submissions

—

P/LP missense

0.16

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.16LOEUF

pLI 1.000

Z-score 5.59

OE 0.05 (0.02–0.16)

Highly constrained

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

Missense Constraint?

1.44Z-score

OE missense 0.79 (0.72–0.87)

312 obs / 392.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.05 (0.02–0.16)

0≤0.351.4

Missense OE?0.79 (0.72–0.87)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 2 / 40.2Missense obs/exp: 312 / 392.5Syn Z: -0.31

Background carrier burden — how many people carry a rare variant somewhere in INTS10?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 99

903 rare PASS variants

Rare truncating (LoF)

1 in 3,400

91 rare PASS variants

Rare synonymous (reference)

1 in 150

351 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for INTS10. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 120	1 in 3,200
South Asian	~43k	1 in 110	1 in 1,300
Remaining (unassigned)	~30k	1 in 87	1 in 6,000
European (Finnish)	~27k	1 in 250	≈ 1 in 27,000
Admixed American	~22k	1 in 71	≈ 1 in 10,000
African / African American	~21k	1 in 73	≈ 1 in 21,000
East Asian	~20k	1 in 91	≈ 1 in 6,600
Ashkenazi Jewish	~13k	1 in 390	1 in 1,200
Middle Eastern	~2,884	1 in 110	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 14 of 17 coding exons well covered in gnomAD exomes; exons 5, 6, 11 marginal. Genomes: all 17.? see exons ↓