RNASET2
protein-codingribonuclease T2
Gene summary
This ribonuclease gene is a novel member of the Rh/T2/S-glycoprotein class of extracellular ribonucleases. It is a single copy gene that maps to 6q27, a region associated with human malignancies and chromosomal rearrangement. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~35.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0013058
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0013058
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0013058
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0013058
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0013058
Submitter: Illumina
Inheritance Pattern: AR
Disease ID:MONDO:0013058
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Audiologic/Otolaryngologic; Neurologic
Intervention: Audiologic/Otolaryngologic
Rationale: Early recognition and treatment of hearing impairment may possibly benefit developmental outcomes in some individuals, including speech and language development
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to RNASET2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003730.6. 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 | 2 | 37 | 3 | 42 | ||
| missense | 1 | 58 | 8 | 2 | 69 | |
| nonsense | 2 | 1 | 1 | 4 | ||
| start loss | 0 | |||||
| frameshift | 2 | 2 | ||||
| splice donor/acceptor (+/-2bp) | 5 | 3 | 4 | 12 | ||
| Total | 8 | 6 | 65 | 45 | 5 | 129 |
Highest pathogenic variant AF is 0.0016803306
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003721.2 | 9 | MANE Select | |
| Ensembl | ENSP00000426455.2 | 9 | MANE Select | |
| Ensembl | ENSP00000028008.5 | 4 | Standard | |
| Ensembl | ENSP00000424947.1 | 8 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| rnaset2 | Danio rerio | Structure: CNS neuron (sensu Vertebrata) Quality: increased size abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Neutrophil degranulation
- Innate Immune System
- Immune System
Biological Process
- RNA catabolic process
- neutrophil degranulation
- RNA phosphodiester bond hydrolysis, endonucleolytic
Molecular Function
- RNA binding
- endoribonuclease activity
- ribonuclease activity
- ribonuclease T2 activity
Cellular Component
- extracellular region
- extracellular space
- lysosome
- endoplasmic reticulum lumen
- azurophil granule lumen
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000508775
- Coding exons
- 9
- Length
- 27688
- Individuals with no LoFs
- 125730
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 18
- Defined
- 125748
- p
- 0.0000716
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.243 | 133 | 141 | 0.942 | 0.00000748 | 1670 |
| Missense (PolyPhen) | 36 | 45.915 | 0.78405 | 596 | ||
| Synonymous | -0.445 | 62 | 57.7 | 1.07 | 0.00000361 | 463 |
| Loss of Function | 1.68 | 8 | 15.0 | 0.533 | 6.41e-7 | 168 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00014 | 0.00013 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Has ribonuclease activity, with higher activity at acidic pH. Probably is involved in lysosomal degradation of ribosomal RNA (By similarity). Probably plays a role in cellular RNA catabolism. {ECO:0000250, ECO:0000269|PubMed:16620762, ECO:0000269|PubMed:19525954, ECO:0000269|PubMed:22735700}.;
Recessive Scores
- pRec
- 0.102
Intolerance Scores
- LoFtool
- 0.546
- RVIS EVS
- 0.55
- RVIS percentile EVS
- 81.38
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.217
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |