INTS3

Chr 1

integrator complex subunit 3

Also known as: C1orf193, C1orf60, INT3, SOSS-A, SOSSA

NCBI Gene: 65123 ENSG00000143624 UniProt: Q68E01

The protein encoded by this gene can form a complex with human single-strand DNA binding proteins 1 or 2 (hSSB1 and hSSB2) and other proteins to mediate genome stability and the DNA damage response. The encoded protein is also part of a multiprotein complex that interacts with the C-terminal domain of RNA polymerase II large subunit to help regulate processing of U1 and U2 small nuclear RNAs. [provided by RefSeq, May 2016]

Research

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.25

Clinical Summary— INTS3

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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.

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ClinVar Variants

55 VUS of 112 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.25LOEUF

pLI 1.000

Z-score 6.48

OE 0.15 (0.09–0.25)

Highly constrained

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

Missense Constraint?

4.41Z-score

OE missense 0.49 (0.45–0.54)

293 obs / 596.4 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.15 (0.09–0.25)

0≤0.351.4

Missense OE?0.49 (0.45–0.54)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 10 / 67.5Missense obs/exp: 293 / 596.4Syn Z: 1.07

This gene — mechanism propensity

0.2798th %ile

GOF

0.3788th %ile

LOF

0.73top 10%

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

LOFprediction above median · LOEUF 0.25

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

112 submitted variants in ClinVar

ClinVar

Classification Summary

VUS55

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	55	55
Likely Benign	0	0
Benign	0	0
Total	55	55

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

View in ClinVar →

11 pathogenic / likely-pathogenic (of 24) ClinVar copy-number / structural variants overlap INTS3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →