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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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RCHY1
ring finger and CHY zinc finger domain containing 1
Chromosome 4 · 4q21.1
NCBI Gene: 25898Ensembl: ENSG00000163743.15HGNC: HGNC:17479UniProt: Q96PM5
94PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cytosolubiquitin ligase complexprotein bindingzinc ion bindingJaundiceNon-Neoplastic Bile Duct Disorderpituitary gland diseasesystemic lupus erythematosus
✦AI Summary

RCHY1 (ring finger and CHY zinc finger domain containing 1) is an E3 ubiquitin ligase with multiple cellular roles in protein degradation and quality control. Primary function: RCHY1 mediates ubiquitin-dependent degradation of target proteins including p53 and HDAC2 12. In melanophagy, RCHY1 functions as an essential E3 ligase required for selective autophagy-mediated degradation of melanosomes, working alongside autophagy receptor OPTN 3. Mechanism: RCHY1 contains a RING-finger domain enabling ubiquitin ligase activity 2. Its stability and activity are regulated by protein interactions—viral SARS proteases (PLpro and SUD) stabilize RCHY1 to promote p53 degradation and suppress antiviral immunity 14, while Hoxa2 transcription factor promotes RCHY1 proteasomal degradation independent of ubiquitin 56. Disease relevance: RCHY1 dysregulation impacts cancer pathogenesis; inverse RCHY1-HDAC2 correlation exists in tumors 2. PHB2-RCHY1 signaling promotes colon cancer proliferation, and targeting this pathway enhances drug cytotoxicity 7. RCHY1 additionally participates in ribosome-associated quality control targeting polyalanine-tailed substrates 8. Clinical significance: RCHY1 represents a therapeutic target for pigmentation disorders and cancer treatment strategies.

Sources cited
1
RCHY1 is an essential E3 ligase for melanophagy, selective autophagy-mediated degradation of melanosomes
PMID: 38899611
2
RCHY1 interacts with viral SUD and PLpro domains, mediates p53 ubiquitination and degradation, antagonizes antiviral immunity
PMID: 27519799
3
Viral PLpro stabilizes RCHY1 to promote ubiquitination of p53 and other target proteins
PMID: 33368679
4
RCHY1 is an E3 ligase that negatively regulates HDAC2; inverse correlation between RCHY1 and HDAC2 levels in tumor tissues
PMID: 31630802
5
Hoxa2 transcription factor promotes proteasome-dependent degradation of RCHY1 and stabilization of p53
PMID: 24244684
6
Hoxa2-mediated RCHY1 degradation involves 19S and 20S proteasome complexes and is evolutionarily conserved
PMID: 26496426
7
PHB2-RCHY1 signaling promotes colon cancer proliferation; targeting PHB2-RCHY1 pathway enhances oxaliplatin cytotoxicity
PMID: 36342357
8
RCHY1 homolog Pirh2 recognizes polyalanine-tail degrons in ribosome-associated quality control
PMID: 37676773
Disease Associationsⓘ20
JaundiceOpen Targets
0.27Weak
Non-Neoplastic Bile Duct DisorderOpen Targets
0.13Weak
pituitary gland diseaseOpen Targets
0.12Weak
systemic lupus erythematosusOpen Targets
0.10Suggestive
respiratory system diseaseOpen Targets
0.09Suggestive
musculoskeletal system diseaseOpen Targets
0.09Suggestive
nervous system diseaseOpen Targets
0.09Suggestive
ocular hypotensionOpen Targets
0.09Suggestive
vitamin B12 deficiencyOpen Targets
0.08Suggestive
Alzheimer diseaseOpen Targets
0.08Suggestive
Miyoshi myopathyOpen Targets
0.08Suggestive
frozen shoulderOpen Targets
0.07Suggestive
oral squamous cell carcinomaOpen Targets
0.05Suggestive
hepatocellular carcinomaOpen Targets
0.04Suggestive
cancerOpen Targets
0.04Suggestive
multiple myelomaOpen Targets
0.04Suggestive
ovarian neoplasmOpen Targets
0.04Suggestive
type 2 diabetes mellitusOpen Targets
0.03Suggestive
breast diseaseOpen Targets
0.03Suggestive
gliomaOpen Targets
0.03Suggestive
Pathogenic Variants1
NM_015436.4(RCHY1):c.157G>A (p.Asp53Asn)Pathogenic
Hypercholesterolemia, familial, 1
☆☆☆☆2022→ Residue 53
View on ClinVar ↗
Related Genes
RPS27AProtein interaction99%GORABProtein interaction99%ARProtein interaction92%TP53Protein interaction92%UBE2D2Protein interaction92%KAT5Protein interaction92%
Tissue Expression6 tissues
Bone Marrow
100%
Heart
87%
Brain
65%
Ovary
42%
Liver
41%
Lung
36%
Gene Interaction Network
Click a node to explore
RCHY1RPS27AGORABARTP53UBE2D2KAT5
PROTEIN STRUCTURE
Preparing viewer…
PDB7YNX · 2.30 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.83LoF Tolerant
pLIⓘ
0.06Tolerant
Observed/Expected LoF0.49 [0.30–0.83]
RankingsWhere RCHY1 stands among ~20K protein-coding genes
  • #5,100of 20,598
    Most Researched94 · top quartile
  • #4,909of 5,498
    Most Pathogenic Variants1
  • #7,078of 17,882
    Most Constrained (LOEUF)0.83
Genes detectedRCHY1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
RCHY1 and OPTN: an E3-ligase and an autophagy receptor required for melanophagy, respectively.
PMID: 38899611
Autophagy · 2024
1.00
2
Spatial and temporal roles of SARS-CoV PL
PMID: 33368679
FASEB J · 2021
0.90
3
Mechanism and evolutionary origins of alanine-tail C-degron recognition by E3 ligases Pirh2 and CRL2-KLHDC10.
PMID: 37676773
Cell Rep · 2023
0.80
4
Regulation of p73 by Pirh2-AIP4 loop.
PMID: 34520394
Aging (Albany NY) · 2021
0.70
5
p53 down-regulates SARS coronavirus replication and is targeted by the SARS-unique domain and PLpro via E3 ubiquitin ligase RCHY1.
PMID: 27519799
Proc Natl Acad Sci U S A · 2016
0.60