INTS1
protein-codingintegrator complex subunit 1, the group of Armadillo like helical domain containing|Integrator complex
Gene summary
INTS1 is a subunit of the Integrator complex, which associates with the C-terminal domain of RNA polymerase II large subunit (POLR2A; MIM 180660) and mediates 3-prime end processing of small nuclear RNAs U1 (RNU1; MIM 180680) and U2 (RNU2; MIM 180690) (Baillat et al., 2005 [PubMed 16239144]).[supplied by OMIM, Mar 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~34.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0032817
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0032817
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0032817
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0032817
Submitter: G2P
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic
Intervention: General
Rationale: 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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to INTS1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001080453.3. 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 | 7 | 145 | 15 | 167 | ||
| missense | 2 | 1 | 505 | 37 | 3 | 548 |
| nonsense | 3 | 9 | 3 | 15 | ||
| start loss | 0 | |||||
| frameshift | 5 | 5 | 5 | 15 | ||
| splice donor/acceptor (+/-2bp) | 5 | 17 | 22 | |||
| Total | 10 | 20 | 537 | 182 | 18 | 767 |
Highest pathogenic variant AF is 0.000083038874
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001073922.2 | 47 | MANE Select | |
| Ensembl | ENSP00000385722.3 | 47 | MANE Select | |
| Ensembl | ENSP00000419206.1 | 4 | Standard | |
| Ensembl | ENSP00000529146.1 | 47 | 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
- U2 snRNA 3'-end processing
- snRNA transcription by RNA polymerase II
Cellular Component
- nucleoplasm
- membrane
- integral component of membrane
- nuclear membrane
- integrator complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000404767
- Coding exons
- 47
- Length
- 35577
- Individuals with no LoFs
- 124565
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 148
- Defined
- 124713
- p
- 0.000594
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.41 | 1208 | 1.35e+3 | 0.892 | 0.0000930 | 13930 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00055 | 0.00051 | rare |
| Latino/Admixed American | 0.00057 | 0.00055 | rare |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0.00062 | 0.00061 | rare |
| Finnish | 0.00059 | 0.00056 | rare |
| European (Non-Finnish) | 0.00075 | 0.00072 | rare |
| South Asian | 0.00037 | 0.00036 | rare |
| Other | 0.00068 | 0.00066 | rare |
dbNSFP Gene Annotations
Source:
- 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}.;
Intolerance Scores
- LoFtool
- 0.589
- RVIS EVS
- -5.05
- RVIS percentile EVS
- 0.07
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.903
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |