INTS11
protein-codingintegrator complex subunit 11, the group of MBL fold containing DNA/RNA interacting subfamily|MicroRNA protein coding host genes|Integrator complex
Gene summary
The Integrator complex contains at least 12 subunits and associates with the C-terminal domain of RNA polymerase II large subunit (POLR2A; MIM 180660) and mediates the 3-prime end processing of small nuclear RNAs U1 (RNU1; MIM 180680) and U2 (RNU2; MIM 180690). INTS11, or CPSF3L, is the catalytic subunit of the Integrator complex (Baillat et al., 2005 [PubMed 16239144]).[supplied by OMIM, Mar 2008]
- CPSF3L
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~13.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0957386
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0957386
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0100038
Submitter: Ambry Genetics
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 INTS11 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_017871.6. 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 | 13 | 3 | 19 | ||
| missense | 3 | 127 | 4 | 134 | ||
| nonsense | 1 | 1 | ||||
| start loss | 1 | 1 | ||||
| frameshift | 4 | 1 | 5 | |||
| splice donor/acceptor (+/-2bp) | 1 | 6 | 7 | |||
| Total | 4 | 5 | 138 | 17 | 3 | 167 |
Highest pathogenic variant AF is 0.000121506084
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060341.2 | 17 | MANE Select | |
| Ensembl | ENSP00000413493.2 | 17 | MANE Select | |
| RefSeq | NP_001243385.1 | 17 | Standard | |
| RefSeq | NP_001243389.1 | 16 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| ints11 | Danio rerio | Structure: hemopoiesis Quality: disrupted 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 transcription by RNA polymerase II
Molecular Function
- protein binding
- hydrolase activity
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- cytosol
- integrator complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000540437
- Coding exons
- 17
- Length
- 13107
- Individuals with no LoFs
- 125531
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 144
- Defined
- 125675
- p
- 0.000573
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.544 | 357 | 387 | 0.922 | 0.0000251 | 3945 |
| Missense (PolyPhen) | 127 | 160.49 | 0.79132 | 1522 | ||
| Synonymous | -4.01 | 228 | 163 | 1.40 | 0.0000119 | 1150 |
| Loss of Function | 1.58 | 26 | 36.3 | 0.717 | 0.00000218 | 373 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00053 | 0.00049 | rare |
| Latino/Admixed American | 0.00020 | 0.00020 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00061 | 0.00060 | rare |
| Finnish | 0.00037 | 0.00037 | rare |
| European (Non-Finnish) | 0.00074 | 0.00072 | rare |
| South Asian | 0.00062 | 0.00062 | rare |
| Other | 0.0013 | 0.0013 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalytic 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. Mediates the snRNAs 3' cleavage. Mediates recruitment of cytoplasmic dynein to the nuclear envelope, probably as component of the INT complex (PubMed:23904267). {ECO:0000269|PubMed:16239144, ECO:0000269|PubMed:23904267}.;
Recessive Scores
- pRec
- 0.121
Intolerance Scores
- RVIS EVS
- -1.82
- RVIS percentile EVS
- 2.16
Essentials
- Essential (gene trap)
- H