INTS7

protein-coding

integrator complex subunit 7, the group of Armadillo like helical domain containing|Integrator complex

Gene summary

This gene encodes a subunit of the integrator complex. The integrator complex associates with the C-terminal domain of RNA polymerase II and mediates 3'-end processing of the small nuclear RNAs U1 and U2. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

Previous symbols:

C1orf73

MANE transcript

NM_015434.4

Inheritance

—

ClinVar variants

U:117B:1

Top phenotype

INTS7-related disorder

gnomAD constraint

pLI —, LoF o/e 0.37

Max pathogenic AF

—

Genomic locus

chr1:211,940,399-212,035,557

External References & Databases

Ensembl (ENSG00000143493)

Transcript & Mutation Effects

hg38 • Region Span ~95.2 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 INTS7 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 102

INTS7-related disorderTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015434.4. 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			3 clinvar			3
missense			107 clinvar	1 clinvar		108
nonsense			1 clinvar			1
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	117	1	0	118

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 47 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015434.4	RefSeq	NP_056249.1	20	MANE Select
ENST00000366994.8	Ensembl	ENSP00000355961.3	20	MANE Select
NM_001199809.2	RefSeq	NP_001186738.1	19	Standard
NM_001199811.2	RefSeq	NP_001186740.1	20	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
ints7	Danio rerio	Structure: neurocranium Quality: shape abnormal

Gene / Model

Organism

Observed Phenotype

ints7

Danio rerio

Structure: neurocranium

Quality: shape

abnormal

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

DNA damage checkpoint
snRNA processing
snRNA 3'-end processing
snRNA transcription by RNA polymerase II
cellular response to ionizing radiation

Molecular Function

protein binding

Cellular Component

nucleus
nucleoplasm
chromosome
cytoplasm
nuclear body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000366994
Coding exons: 20
Length: 95144
Individuals with no LoFs: 125722
Homozygous LoFs: 0
Heterozygous LoFs: 26
Defined: 125748
p: 0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.13	365	499	0.731	0.0000244	6298
Missense (PolyPhen)		107	178.85	0.59826		2254
Synonymous	0.454	172	180	0.957	0.00000846	1859
Loss of Function	3.99	17	46.3	0.367	0.00000219	587

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000059	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00012	0.00011	rare
South Asian	0.00013	0.00013	rare
Other	0.00033	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). Plays a role in DNA damage response (DDR) signaling during the S phase (PubMed:21659603). May be not involved in the recruitment of cytoplasmic dynein to the nuclear envelope by different components of the INT complex (PubMed:23904267). {ECO:0000269|PubMed:21659603, ECO:0000269|PubMed:23904267, ECO:0000305|PubMed:16239144}.;

Intolerance Scores

LoFtool: 0.410
RVIS EVS: -0.51
RVIS percentile EVS: 21.56

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.977

Gene Damage Prediction

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