INTS1

integrator complex subunit 1, the group of Armadillo like helical domain containing|Integrator complex

Basic information

Region (hg38): 7:1470277-1504389

Links

ENSG00000164880NCBI:26173OMIM:611345HGNC:24555Uniprot:Q8N201AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies (Moderate), mode of inheritance: AR
  • neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Neurodevelopmental disorder with cataracts, poor growth, and dysmorphic faciesARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingCraniofacial; Musculoskeletal; Neurologic; Ophthalmologic28542170; 30622326; 31428919

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the INTS1 gene.

  • not provided (3 variants)
  • Inborn genetic diseases (2 variants)
  • Neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the INTS1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
1
clinvar
76
clinvar
25
clinvar
102
missense
240
clinvar
17
clinvar
5
clinvar
262
nonsense
2
clinvar
2
clinvar
1
clinvar
5
start loss
0
frameshift
4
clinvar
2
clinvar
1
clinvar
7
inframe indel
1
clinvar
1
splice donor/acceptor (+/-2bp)
4
clinvar
4
splice region
6
10
8
24
non coding
2
clinvar
3
clinvar
18
clinvar
23
Total 6 8 245 97 48

Highest pathogenic variant AF is 0.0000132

Variants in INTS1

This is a list of pathogenic ClinVar variants found in the INTS1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
7-1470582-T-G Uncertain significance (Aug 15, 2022)2430428
7-1470586-GGCCTCCATAT-AGGCTCACATCACG Inborn genetic diseases Uncertain significance (Feb 25, 2022)2277337
7-1470588-C-G Inborn genetic diseases Uncertain significance (Jan 19, 2022)2272313
7-1470594-T-C Inborn genetic diseases Uncertain significance (Jan 19, 2022)2400429
7-1470627-C-T Inborn genetic diseases Uncertain significance (Jan 06, 2022)1695545
7-1470645-C-T Inborn genetic diseases Uncertain significance (Feb 11, 2022)2396959
7-1470651-T-C Uncertain significance (Nov 30, 2021)1691135
7-1470686-G-A Uncertain significance (May 18, 2023)1439960
7-1470687-C-T Inborn genetic diseases Uncertain significance (Nov 08, 2022)2323983
7-1470849-G-C Uncertain significance (May 30, 2019)1305883
7-1470858-G-C Inborn genetic diseases Uncertain significance (Jun 03, 2022)2293793
7-1470874-G-T Inborn genetic diseases Uncertain significance (Jul 13, 2021)2236621
7-1470876-T-G Inborn genetic diseases Uncertain significance (Jun 07, 2024)3286204
7-1470887-G-A Inborn genetic diseases Uncertain significance (Dec 11, 2023)3110065
7-1470922-G-C Pathogenic (Dec 19, 2019)643062
7-1470931-C-T INTS1-related disorder Likely benign (Mar 01, 2019)3046580
7-1470934-G-A INTS1-related disorder Likely benign (Jun 18, 2019)3352535
7-1471160-G-A Neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies Uncertain significance (Mar 29, 2024)3065601
7-1471173-C-T Inborn genetic diseases Uncertain significance (Nov 17, 2022)2370360
7-1471181-C-T Inborn genetic diseases Uncertain significance (May 20, 2024)3286185
7-1471184-C-A Inborn genetic diseases Uncertain significance (Oct 13, 2023)3110064
7-1471195-G-A Benign (Dec 31, 2019)781892
7-1471198-C-T Benign (Jun 01, 2024)789292
7-1471212-G-A Inborn genetic diseases Uncertain significance (Jan 17, 2024)3110063
7-1471218-G-A Likely benign (Mar 01, 2024)3234163

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
INTS1protein_codingprotein_codingENST00000404767 4735577
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
7.11e-111.0012456501481247130.000594
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense1.4112081.35e+30.8920.000093013930
Missense in Polyphen210293.530.715442984
Synonymous-6.228286291.320.00004764510
Loss of Function5.98371020.3620.000005071111

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.001130.00109
Ashkenazi Jewish0.0002000.000199
East Asian0.0006220.000612
Finnish0.0005890.000557
European (Non-Finnish)0.0007510.000717
Middle Eastern0.0006220.000612
South Asian0.0003670.000360
Other0.0006750.000660

dbNSFP

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}.;
Pathway
Gene expression (Transcription);RNA polymerase II transcribes snRNA genes;RNA Polymerase II Transcription (Consensus)

Intolerance Scores

loftool
0.589
rvis_EVS
-5.05
rvis_percentile_EVS
0.07

Haploinsufficiency Scores

pHI
0.156
hipred
Y
hipred_score
0.648
ghis
0.645

Essentials

essential_gene_CRISPR
E
essential_gene_CRISPR2
E
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.903

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Ints1
Phenotype
embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span);

Gene ontology

Biological process
snRNA processing;U2 snRNA 3'-end processing;snRNA transcription by RNA polymerase II
Cellular component
nucleoplasm;membrane;integral component of membrane;nuclear membrane;integrator complex
Molecular function