INTS11

Chr 1

integrator complex subunit 11

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

NCBI Gene: 54973ENSG00000127054UniProt: Q5TA45

The Integrator complex contains at least 12 subunits and associates with the C-terminal domain of RNA polymerase II large subunit (POLR2A; MIM 180660) and mediates the 3-prime end processing of small nuclear RNAs U1 (RNU1; MIM 180680) and U2 (RNU2; MIM 180690). INTS11, or CPSF3L, is the catalytic subunit of the Integrator complex (Baillat et al., 2005 [PubMed 16239144]).[supplied by OMIM, Mar 2008]

Primary Disease Associations & Inheritance

UniProtNeurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities
268
ClinVar variants
105
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— INTS11
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
105 Pathogenic / Likely Pathogenic· 140 VUS of 268 total submissions
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?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.99LOEUF
pLI 0.000
Z-score 1.58
OE 0.72 (0.52–0.99)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.54Z-score
OE missense 0.92 (0.84–1.01)
357 obs / 387.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.72 (0.52–0.99)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.84–1.01)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.40
0≤1.21.6
LoF obs/exp: 26 / 36.3Missense obs/exp: 357 / 387.1Syn Z: -4.01

ClinVar Variant Classifications

268 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic94
Likely Pathogenic11
VUS140
Likely Benign16
Benign7
94
Pathogenic
11
Likely Pathogenic
140
VUS
16
Likely Benign
7
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
3
91
0
94
Likely Pathogenic
3
1
7
0
11
VUS
0
118
21
1
140
Likely Benign
0
2
3
11
16
Benign
0
0
3
4
7
Total312412516268

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.

Gene2Phenotype Curations

INTS11-related neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities

moderate
ARLoss Of FunctionAltered Gene Product Structure
Dev. Disorders
G2P ↗
splice region variantframeshift variantstop gainedmissense variantintron variant

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A homozygous variant in INTS11 links mitosis and neurogenesis defects to a severe neurodevelopmental disorder.
Kuang H et al.·Cell Rep
2023
INTS11-related neurodevelopmental disorder: a case report and literature review.
Jiang L et al.·J Hum Genet
2024Review
Neuronal differentiation requires BRAT1 complex to remove REST from chromatin.
Dokaneheifard S et al.·Proc Natl Acad Sci U S A
2024
BRAT1 links Integrator and defective RNA processing with neurodegeneration.
Cihlarova Z et al.·Nat Commun
2022
NACK and INTEGRATOR act coordinately to activate Notch-mediated transcription in tumorigenesis.
Shersher E et al.·Cell Commun Signal
2021
Genome-wide screening for genetic variants in polyadenylation signal (PAS) sites in mouse selection lines for fatness and leanness.
Šimon M et al.·Mamm Genome
2023Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools