INTS8

protein-coding

integrator complex subunit 8, the group of Integrator complex

Gene summary

This gene encodes a subunit of the Integrator complex which is involved in the cleavage of small nuclear RNAs U1 and U2 within the nucleus. The encoded protein associates with RNA polymerase II and is recruited to the U1 and U2 small nuclear RNA genes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

Previous symbols:

C8orf52

MANE transcript

NM_017864.4

Inheritance

ClinVar variants

P:2U:124B:15

Top phenotype

INTS8-related disorder

gnomAD constraint

pLI —, LoF o/e 0.19

Max pathogenic AF

—

Genomic locus

chr8:94,813,311-94,881,746

External References & Databases

Ensembl (ENSG00000164941)

Transcript & Mutation Effects

hg38 • Region Span ~68.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorder with cerebellar hypoplasia and spasticityLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0032818

Submitter: Labcorp Genetics (formerly Invitae)

neurodevelopmental disorder with cerebellar hypoplasia and spasticityLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0032818

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to INTS8 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 98

INTS8-related disorderTotal: 12

not providedTotal: 11

Neurodevelopmental disorder with cerebellar hypoplasia and spasticityTotal: 5

Prostate cancerTotal: 1

Long QT syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017864.4. 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	7 clinvar	1 clinvar	10
missense	1 clinvar		111 clinvar	7 clinvar		119
nonsense		1 clinvar				1
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			9 clinvar			9
Total	1	1	124	14	1	141

Highest pathogenic variant AF is 0.0000018650709

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 17 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017864.4	RefSeq	NP_060334.2	27	MANE Select
ENST00000523731.6	Ensembl	ENSP00000430338.1	27	MANE Select
ENST00000343161.8	Ensembl	ENSP00000343274.4	18	Standard
ENST00000519053.5	Ensembl	ENSP00000429056.1	4	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

nucleoplasm
integrator complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000523731
Coding exons: 27
Length: 68436
Individuals with no LoFs: 125727
Homozygous LoFs: 0
Heterozygous LoFs: 21
Defined: 125748
p: 0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.03	384	513	0.748	0.0000253	6523
Missense (PolyPhen)		120	201.16	0.59653		2587
Synonymous	-0.0832	182	181	1.01	0.00000922	1841
Loss of Function	5.88	12	62.0	0.194	0.00000326	755

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00011	0.000099	rare
East Asian	0	0.0	absent
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00013	0.00013	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the Integrator 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.;

Recessive Scores

pRec: 0.132

Intolerance Scores

RVIS EVS: -0.57
RVIS percentile EVS: 18.9

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): H
Indispensability pred.: E
Indispensability score: 0.772

Gene Damage Prediction

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