RCHY1
protein-codingring finger and CHY zinc finger domain containing 1, the group of Ring finger proteins
Gene summary
The protein encoded by this gene has ubiquitin ligase activity. It mediates E3-dependent ubiquitination and proteasomal degradation of target proteins, including tumor protein 53, histone deacetylase 1, and cyclin-dependent kinase inhibitor 1B, thus regulating their levels and cell cycle progression. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jun 2013]
- ZNF363
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~35.7 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 RCHY1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015436.4. 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 | 2 | 1 | 5 | ||
| missense | 1 | 22 | 3 | 26 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 1 | 0 | 26 | 5 | 1 | 33 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_056251.2 | 9 | MANE Select | |
| Ensembl | ENSP00000321239.5 | 9 | MANE Select | |
| RefSeq | NP_001009922.1 | 8 | Standard | |
| RefSeq | NP_001265465.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- p53 signaling pathway - Homo sapiens (human)
- Ubiquitin mediated proteolysis - Homo sapiens (human)
- Measles - Homo sapiens (human)
- DNA Repair
- Immune System
Biological Process
- ubiquitin-dependent protein catabolic process
- protein ubiquitination
- positive regulation of protein ubiquitination
- positive regulation of proteasomal ubiquitin-dependent protein catabolic process
- error-free translesion synthesis
Molecular Function
- p53 binding
- ubiquitin-protein transferase activity
- protein binding
- zinc ion binding
- protein homodimerization activity
Cellular Component
- ubiquitin ligase complex
- nucleus
- nucleoplasm
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000324439
- Coding exons
- 9
- Length
- 35728
- Individuals with no LoFs
- 125712
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 36
- Defined
- 125748
- p
- 0.000143
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.20 | 101 | 141 | 0.715 | 0.00000701 | 1737 |
| Missense (PolyPhen) | 32 | 66.802 | 0.47903 | 798 | ||
| Synonymous | 1.04 | 37 | 46.0 | 0.805 | 0.00000218 | 427 |
| Loss of Function | 2.63 | 5 | 16.5 | 0.302 | 7.81e-7 | 221 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00055 | 0.00049 | rare |
| Latino/Admixed American | 0.00026 | 0.00023 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.00019 | 0.00018 | rare |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.000067 | 0.000065 | rare |
| Other | 0.00021 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Mediates E3-dependent ubiquitination and proteasomal degradation of target proteins, including p53/TP53, P73, HDAC1 and CDKN1B. Preferentially acts on tetrameric p53/TP53. Monoubiquitinates the translesion DNA polymerase POLH. Contributes to the regulation of the cell cycle progression. Increases AR transcription factor activity. {ECO:0000269|PubMed:16914734, ECO:0000269|PubMed:17721809, ECO:0000269|PubMed:18006823, ECO:0000269|PubMed:19043414, ECO:0000269|PubMed:19483087, ECO:0000269|PubMed:21791603, ECO:0000269|PubMed:21994467}.;
Recessive Scores
- pRec
- 0.194
Intolerance Scores
- LoFtool
- 0.489
- RVIS EVS
- -0.3
- RVIS percentile EVS
- 32.62
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.905
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |