INTS5

Chr 11

integrator complex subunit 5

Also known as: INT5, KIAA1698

NCBI Gene: 80789 ENSG00000185085 UniProt: Q6P9B9

INTS5 encodes a component of the integrator complex that terminates RNA polymerase II transcription and processes small nuclear RNAs and other non-coding transcripts. Mutations cause autosomal recessive neurodevelopmental disorder with intellectual disability, seizures, and movement abnormalities with infantile to early childhood onset. The gene shows significant constraint against loss-of-function variants (LOEUF 0.42), indicating intolerance to haploinsufficiency.

ResearchSummary from RefSeq, UniProt

The Integrator complex is a complex that associates with the C-terminal domain of RNA polymerase II large subunit. This complex is brought to U1 and U2 small nuclear RNA genes, where it is involved in the transcription and processing of their transcripts. The protein encoded by this gene represents a subunit of the Integrator complex. [provided by RefSeq, Aug 2016]

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

0.42

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.42LOEUF

pLI 0.513

Z-score 3.87

OE 0.21 (0.12–0.42)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.73Z-score

OE missense 0.80 (0.74–0.86)

466 obs / 583.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.21 (0.12–0.42)

0≤0.351.4

Missense OE?0.80 (0.74–0.86)

0≤0.61.4

Synonymous OE?1.12

0≤1.21.6

LoF obs/exp: 6 / 28.2Missense obs/exp: 466 / 583.8Syn Z: -1.42

Background carrier burden — how many people carry a rare variant somewhere in INTS5?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 68

1,206 rare PASS variants

Rare truncating (LoF)

1 in 4,900

77 rare PASS variants

Rare synonymous (reference)

1 in 76

624 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for INTS5. 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 92	1 in 4,700
South Asian	~43k	1 in 53	≈ 1 in 22,000
Remaining (unassigned)	~30k	1 in 50	none seen
European (Finnish)	~27k	1 in 190	1 in 3,300
Admixed American	~22k	1 in 62	≈ 1 in 11,000
African / African American	~21k	1 in 66	1 in 2,700
East Asian	~20k	1 in 56	≈ 1 in 9,900
Ashkenazi Jewish	~13k	1 in 350	≈ 1 in 4,400
Middle Eastern	~2,884	1 in 43	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): 1 of 2 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 2.? see exons ↓