INTS11

Chr 1AR

integrator complex subunit 11

Also known as: CPSF3L, CPSF73L, INT11, NEDMLOB, PSF3L, RC-68, RC68

INTS11 encodes the RNA endonuclease subunit of the Integrator complex, which terminates RNA polymerase II transcription and processes small nuclear RNAs. Biallelic mutations cause autosomal recessive neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities. This gene is extremely intolerant to loss-of-function variants (pLI ~1.0), indicating that even heterozygous loss is typically incompatible with normal development.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.991 OMIM phenotype
Clinical SummaryINTS11
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
99 unique Pathogenic / Likely Pathogenic· 85 VUS of 200 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.99LOEUF
pLI 0.000
Z-score 1.58
OE 0.72 (0.520.99)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.54Z-score
OE missense 0.92 (0.841.01)
357 obs / 387.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.72 (0.520.99)
00.351.4
Missense OE0.92 (0.841.01)
00.61.4
Synonymous OE1.40
01.21.6
LoF obs/exp: 26 / 36.3Missense obs/exp: 357 / 387.1Syn Z: -4.01
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateINTS11-related neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalitiesLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6454th %ile
GOF
0.5367th %ile
LOF
0.4135th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

200 submitted variants in ClinVar

Classification Summary

Pathogenic89
Likely Pathogenic10
VUS85
Likely Benign8
Benign7
Conflicting1
89
Pathogenic
10
Likely Pathogenic
85
VUS
8
Likely Benign
7
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
3
86
0
89
Likely Pathogenic
2
1
7
0
10
VUS
0
65
20
0
85
Likely Benign
0
2
1
5
8
Benign
0
0
3
4
7
Conflicting
1
Total2711179200

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

View in ClinVar →

Protein Context — Lollipop Plot

INTS11 · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗