INTS2

protein-coding

integrator complex subunit 2, the group of Integrator complex

Gene summary

INTS2 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]

Previous symbols:

KIAA1287

MANE transcript

NM_001351695.2

Inheritance

—

ClinVar variants

U:135B:5

Top phenotype

INTS2-related disorder

gnomAD constraint

pLI —, LoF o/e 0.16

Max pathogenic AF

—

Genomic locus

chr17:61,865,367-61,928,016

External References & Databases

Ensembl (ENSG00000108506)

Transcript & Mutation Effects

hg38 • Region Span ~62.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to INTS2 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 124

not providedTotal: 2

INTS2-related disorderTotal: 2

Exstrophy-epispadias complexTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001351695.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	1 clinvar		3
missense			131 clinvar	3 clinvar	1 clinvar	135
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	135	4	1	140

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 31 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001351695.2	RefSeq	NP_001338624.2	24	MANE Select
ENST00000251334.7	Ensembl	ENSP00000251334.6	24	MANE Select
NM_001330417.2	RefSeq	NP_001317346.2	24	Standard
NM_020748.4	RefSeq	NP_065799.2	25	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Gene expression (Transcription)
RNA polymerase II transcribes snRNA genes
RNA Polymerase II Transcription

Biological Process

snRNA processing
snRNA 3'-end processing
snRNA transcription by RNA polymerase II

Molecular Function

protein binding

Cellular Component

nucleus
nucleoplasm
cytoplasm
membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000444766
Coding exons: 25
Length: 62647
Individuals with no LoFs: 124628
Homozygous LoFs: 0
Heterozygous LoFs: 31
Defined: 124659
p: 0.000124

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.26	459	617	0.744	0.0000318	7836
Missense (PolyPhen)		134	232.64	0.57599		2973
Synonymous	1.55	185	214	0.865	0.0000108	2315
Loss of Function	6.06	10	61.1	0.164	0.00000331	741

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000065	0.000065	rare
Latino/Admixed American	0.000063	0.000058	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0.00019	0.00019	rare
European (Non-Finnish)	0.00015	0.00015	rare
South Asian	0.000078	0.000065	rare
Other	0.00034	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the Integrator (INT) complex, a complex involved in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing. The Integrator complex is associated with the C-terminal domain (CTD) of RNA polymerase II largest subunit (POLR2A) and is recruited to the U1 and U2 snRNAs genes (Probable). Mediates recruitment of cytoplasmic dynein to the nuclear envelope, probably as component of the INT complex (PubMed:23904267). {ECO:0000269|PubMed:23904267, ECO:0000305|PubMed:16239144}.;

Recessive Scores

pRec: 0.130

Intolerance Scores

RVIS EVS: -0.62
RVIS percentile EVS: 17.36

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.781

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium