INTS6

Chr 13

integrator complex subunit 6

Also known as: DBI-1, DDX26, DDX26A, DICE1, HDB, INT6, Notchl2

INTS6 encodes a component of the integrator complex that regulates RNA polymerase II transcription termination and processes small nuclear RNAs, acting as a molecular adapter to recruit protein phosphatase 2A to transcription checkpoints. Mutations cause autosomal dominant developmental delay with variable intellectual disability and behavioral abnormalities, typically presenting in early childhood. This gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely incompatible with normal development.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.14
Clinical SummaryINTS6
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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.14LOEUF
pLI 1.000
Z-score 6.03
OE 0.04 (0.020.14)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
3.83Z-score
OE missense 0.50 (0.450.56)
233 obs / 465.7 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.04 (0.020.14)
00.351.4
Missense OE0.50 (0.450.56)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 2 / 46.3Missense obs/exp: 233 / 465.7Syn Z: -1.05
DN
0.3792th %ile
GOF
0.3788th %ile
LOF
0.78top 5%

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

LOFprediction above median · LOEUF 0.14

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

INTS6 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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