RNASE4
protein-codingribonuclease A family member 4, the group of Ribonuclease A family
Gene summary
The protein encoded by this gene belongs to the pancreatic ribonuclease family. It plays an important role in mRNA cleavage and has marked specificity towards the 3' side of uridine nucleotides. Alternative splicing results in four transcript variants encoding the same protein. This gene and the gene that encodes angiogenin share promoters and 5' exons. Each gene splices to a unique downstream exon that contains its complete coding region. [provided by RefSeq, Aug 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~16.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to RNASE4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002937.5. 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 | 0 | |||||
| missense | 26 | 26 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 26 | 0 | 0 | 26 |
Highest pathogenic variant AF is 0.000017967024
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002928.1 | 1 | MANE Select | |
| Ensembl | ENSP00000452245.1 | 1 | MANE Select | |
| RefSeq | NP_001269121.1 | 1 | Standard | |
| RefSeq | NP_001269122.1 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- mRNA cleavage
- RNA phosphodiester bond hydrolysis, endonucleolytic
Molecular Function
- nucleic acid binding
- ribonuclease A activity
- ribonuclease activity
Cellular Component
- extracellular region
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000555835
- Coding exons
- 1
- Length
- 16503
- Individuals with no LoFs
- 125721
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 23
- Defined
- 125745
- p
- 0.0000954
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0318 | 89 | 88.2 | 1.01 | 0.00000549 | 967 |
| Missense (PolyPhen) | 23 | 27.55 | 0.83484 | 357 | ||
| Synonymous | -1.22 | 42 | 33.0 | 1.27 | 0.00000184 | 291 |
| Loss of Function | -0.527 | 5 | 3.88 | 1.29 | 2.52e-7 | 41 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.00030 | 0.00030 | rare |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00013 | 0.00012 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: This RNase has marked specificity towards the 3' side of uridine nucleotides.;
Intolerance Scores
- RVIS EVS
- 0.93
- RVIS percentile EVS
- 89.66
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.983
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |