INTS4

Chr 11

integrator complex subunit 4

Also known as: INT4, MST093

NCBI Gene: 92105 ENSG00000149262 UniProt: Q96HW7

INTS4 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]

Research

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.70

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

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.70LOEUF

pLI 0.000

Z-score 3.33

OE 0.51 (0.37–0.70)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.25Z-score

OE missense 0.84 (0.78–0.91)

433 obs / 512.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.51 (0.37–0.70)

0≤0.351.4

Missense OE?0.84 (0.78–0.91)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

LoF obs/exp: 27 / 53.2Missense obs/exp: 433 / 512.8Syn Z: 1.38

Background carrier burden — how many people carry a rare variant somewhere in INTS4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 66

986 rare PASS variants

Rare truncating (LoF)

1 in 930

137 rare PASS variants

Rare synonymous (reference)

1 in 110

360 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for INTS4. 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 76	1 in 870
South Asian	~43k	1 in 54	1 in 910
Remaining (unassigned)	~30k	1 in 50	1 in 1,100
European (Finnish)	~27k	1 in 170	1 in 620
Admixed American	~22k	1 in 65	1 in 1,000
African / African American	~21k	1 in 75	1 in 1,100
East Asian	~20k	1 in 76	1 in 730
Ashkenazi Jewish	~13k	1 in 350	≈ 1 in 6,400
Middle Eastern	~2,884	1 in 75	≈ 1 in 1,400

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): 16 of 23 coding exons well covered in gnomAD exomes; exons 3, 4, 6, 7, 12 and 2 more marginal. Genomes: 21 of 23 (exons 5, 6 below).? see exons ↓