INTS6

protein-coding

integrator complex subunit 6, the group of Integrator complex

Gene summary

DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. The protein encoded by this gene is a DEAD box protein that is part of a complex that interacts with the C-terminus of RNA polymerase II and is involved in 3' end processing of snRNAs. In addition, this gene is a candidate tumor suppressor and is located in the critical region of loss of heterozygosity (LOH). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2015]

Previous symbols:

DDX26

MANE transcript

NM_012141.3

Inheritance

—

ClinVar variants

P:9U:91B:6

Top phenotype

INTS6-related disorder

gnomAD constraint

pLI —, LoF o/e 0.04

Max pathogenic AF

—

Genomic locus

chr13:51,354,077-51,454,264

External References & Databases

Ensembl (ENSG00000102786)

Transcript & Mutation Effects

hg38 • Region Span ~100.2 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 INTS6 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 67

not providedTotal: 19

INTS6-related disorderTotal: 13

INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 78Total: 4

INTS6-associated neurodevelopmental disorderTotal: 1

Autism spectrum disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012141.3. 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			1 clinvar	2 clinvar	2 clinvar	5
missense	2 clinvar	2 clinvar	73 clinvar	1 clinvar	1 clinvar	79
nonsense	2 clinvar		6 clinvar			8
start loss						0
frameshift	2 clinvar	1 clinvar	4 clinvar			7
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	6	3	91	3	3	106

Highest pathogenic variant AF is 6.846295e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 39 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012141.3	RefSeq	NP_036273.1	18	MANE Select
ENST00000311234.9	Ensembl	ENSP00000310260.4	18	MANE Select
NM_001039937.2	RefSeq	NP_001035026.1	18	Standard
NM_001039938.2	RefSeq	NP_001035027.1	3	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
ints6	Danio rerio	Structure: whole organism Quality: radial symmetry abnormal

Gene / Model

Organism

Observed Phenotype

ints6

Danio rerio

Structure: whole organism

Quality: radial symmetry

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

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

Molecular Function

transmembrane signaling receptor activity
protein binding

Cellular Component

nucleus
nucleoplasm
actin cytoskeleton
integrator complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000311234
Coding exons: 18
Length: 100188
Individuals with no LoFs: 125694
Homozygous LoFs: 0
Heterozygous LoFs: 4
Defined: 125698
p: 0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.83	233	466	0.500	0.0000228	5822
Missense (PolyPhen)		55	185.56	0.2964		2461
Synonymous	-1.05	175	158	1.11	0.00000750	1678
Loss of Function	6.03	2	46.3	0.0432	0.00000254	569

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000059	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000055	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

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). May have a tumor suppressor role; an ectopic expression suppressing tumor cell growth (PubMed:15254679, PubMed:16239144). {ECO:0000269|PubMed:15254679, ECO:0000269|PubMed:16239144, ECO:0000269|PubMed:23904267, ECO:0000305|PubMed:16239144}.;

Recessive Scores

pRec: 0.171

Intolerance Scores

LoFtool: 0.0140
RVIS EVS: -0.87
RVIS percentile EVS: 10.73

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): H
Indispensability pred.: E
Indispensability score: 0.614

Gene Damage Prediction

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