INTS1

Chr 7AR

integrator complex subunit 1

Also known as: INT1, NDCAGF, NET28

NCBI Gene: 26173 ENSG00000164880 UniProt: Q8N201 OMIM: 611345

INTS1 encodes a subunit of the Integrator complex that terminates RNA polymerase II transcription and processes small nuclear RNAs, with the gene being highly constrained against loss-of-function variants (pLI ~1.0, LOEUF 0.476). Mutations cause autosomal recessive neurodevelopmental disorder with intellectual disability and variable features including hypotonia, seizures, and brain abnormalities. The disorder typically presents in infancy with developmental delays and affects the central nervous system primarily.

OMIM ResearchSummary from RefSeq, UniProt

INTS1 is a subunit of the Integrator complex, which associates with the C-terminal domain of RNA polymerase II large subunit (POLR2A; MIM 180660) and mediates 3-prime end processing of small nuclear RNAs U1 (RNU1; MIM 180680) and U2 (RNU2; MIM 180690) (Baillat et al., 2005 [PubMed 16239144]).[supplied by OMIM, Mar 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.481 OMIM phenotype

Clinical Summary— INTS1

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Population Constraint (gnomAD)

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

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ClinVar Variants

24 unique Pathogenic / Likely Pathogenic· 511 VUS of 806 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.48LOEUF

pLI 0.000

Z-score 5.98

OE 0.36 (0.28–0.48)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.41Z-score

OE missense 0.89 (0.85–0.94)

1208 obs / 1353.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.36 (0.28–0.48)

0≤0.351.4

Missense OE?0.89 (0.85–0.94)

0≤0.61.4

Synonymous OE?1.32

0≤1.21.6

LoF obs/exp: 37 / 102.2Missense obs/exp: 1208 / 1353.9Syn Z: -6.22

ClinVar Variant Classifications

806 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11

Likely Pathogenic13

VUS511

Likely Benign146

Benign51

Conflicting11

Pathogenic

Likely Pathogenic

511

VUS

146

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	9	2	0	0	11
Likely Pathogenic	13	0	0	0	13
VUS	4	491	12	4	511
Likely Benign	2	25	9	110	146
Benign	0	5	24	22	51
Conflicting	—				11
Total	28	523	45	136	743

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

View in ClinVar →

39 pathogenic / likely-pathogenic (of 57) ClinVar copy-number / structural variants overlap INTS1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →