INTS11

Chr 1

integrator complex subunit 11

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

NCBI Gene: 54973 ENSG00000127054 UniProt: Q5TA45

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.

ResearchSummary from RefSeq, OMIM, UniProt

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]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.99

Clinical Summary— INTS11

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

9 unique Pathogenic / Likely Pathogenic· 125 VUS of 189 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

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.99LOEUF

pLI 0.000

Z-score 1.58

OE 0.72 (0.52–0.99)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.54Z-score

OE missense 0.92 (0.84–1.01)

357 obs / 387.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.72 (0.52–0.99)

0≤0.351.4

Missense OE?0.92 (0.84–1.01)

0≤0.61.4

Synonymous OE?1.40

0≤1.21.6

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

This gene — mechanism propensity

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

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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

189 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4

Likely Pathogenic5

VUS125

Likely Benign18

Benign5

Conflicting1

Pathogenic

Likely Pathogenic

125

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	3	0	0	4
Likely Pathogenic	4	1	0	0	5
VUS	1	122	1	1	125
Likely Benign	0	2	3	13	18
Benign	0	0	1	4	5
Conflicting	—				1
Total	6	128	5	18	158

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

View in ClinVar →

132 pathogenic / likely-pathogenic (of 155) ClinVar copy-number / structural variants overlap INTS11 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →