INTS1

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

Basic information

Region (hg38): 7:1470276-1504389

Links

ENSG00000164880 ∙ NCBI:26173 ∙ OMIM:611345 ∙ HGNC:24555 ∙ Uniprot:Q8N201 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	28542170; 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	76	25	102
missense			240	17	5	262
nonsense	2	2	1			5
start loss						0
frameshift	4	2	1			7
inframe indel				1		1
splice donor/acceptor (+/-2bp)		4				4
splice region			6	10	8	24
non coding			2	3	18	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)
7-1470586-GGCCTCCATAT-AGGCTCACATCACG		Inborn genetic diseases	Uncertain significance (Feb 25, 2022)
7-1470588-C-G		Inborn genetic diseases	Uncertain significance (Jan 19, 2022)
7-1470594-T-C		Inborn genetic diseases	Uncertain significance (Jan 19, 2022)
7-1470627-C-T		Inborn genetic diseases	Uncertain significance (Jan 06, 2022)
7-1470645-C-T		Inborn genetic diseases	Uncertain significance (Feb 11, 2022)
7-1470651-T-C			Uncertain significance (Nov 30, 2021)
7-1470686-G-A			Uncertain significance (May 18, 2023)
7-1470687-C-T		Inborn genetic diseases	Uncertain significance (Nov 08, 2022)
7-1470849-G-C			Uncertain significance (May 30, 2019)
7-1470858-G-C		Inborn genetic diseases	Uncertain significance (Jun 03, 2022)
7-1470874-G-T		Inborn genetic diseases	Uncertain significance (Jul 13, 2021)
7-1470876-T-G		Inborn genetic diseases	Uncertain significance (Jun 07, 2024)
7-1470887-G-A		Inborn genetic diseases	Uncertain significance (Dec 11, 2023)
7-1470922-G-C			Pathogenic (Dec 19, 2019)
7-1470931-C-T		INTS1-related disorder	Likely benign (Mar 01, 2019)
7-1471160-G-A		Neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies	Uncertain significance (Mar 29, 2024)
7-1471173-C-T		Inborn genetic diseases	Uncertain significance (Nov 17, 2022)
7-1471181-C-T		Inborn genetic diseases	Uncertain significance (May 20, 2024)
7-1471184-C-A		Inborn genetic diseases	Uncertain significance (Oct 13, 2023)
7-1471195-G-A			Benign (Dec 31, 2019)
7-1471198-C-T			Benign (Jun 01, 2024)
7-1471212-G-A		Inborn genetic diseases	Uncertain significance (Jan 17, 2024)
7-1471218-G-A			Likely benign (Mar 01, 2024)
7-1471229-C-G			Uncertain significance (Jun 29, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
INTS1	protein_coding	protein_coding	ENST00000404767	47	35577

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.11e-11	1.00	124565	0	148	124713	0.000594

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.41	1208	1.35e+3	0.892	0.0000930	13930
Missense in Polyphen		210	293.53	0.71544		2984
Synonymous	-6.22	828	629	1.32	0.0000476	4510
Loss of Function	5.98	37	102	0.362	0.00000507	1111

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00113	0.00109
Ashkenazi Jewish	0.000200	0.000199
East Asian	0.000622	0.000612
Finnish	0.000589	0.000557
European (Non-Finnish)	0.000751	0.000717
Middle Eastern	0.000622	0.000612
South Asian	0.000367	0.000360
Other	0.000675	0.000660

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

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

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