INTS2

Chr 17

integrator complex subunit 2

Also known as: INT2, KIAA1287

NCBI Gene: 57508 ENSG00000108506 UniProt: Q9H0H0

INTS2 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]

Active trials

Pathogenic / LP

ClinVar variants

Pubs (1 yr)

2.3

Missense Z

0.28

LOEUF· LoF intolerant

Clinical Summary— INTS2

⚡

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.

Some data sources returned errors (1)

pubtator: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint

0.28LOEUF

pLI 0.997

Z-score 6.06

OE 0.16 (0.10–0.28)

Highly constrained

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

Missense Constraint

2.26Z-score

OE missense 0.74 (0.69–0.80)

459 obs / 617.3 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios

LoF OE0.16 (0.10–0.28)

0≤0.351.4

Missense OE0.74 (0.69–0.80)

0≤0.61.4

Synonymous OE0.87

0≤1.21.6

LoF obs/exp: 10 / 61.1Missense obs/exp: 459 / 617.3Syn Z: 1.55

LOF

Badonyi & Marsh 2024 ↗

0.3594th %ile

GOF

0.4480th %ile

LOF

0.72top 10%

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

LOFprediction above median · LOEUF 0.28

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.