RC3H2
protein-codingring finger and CCCH-type domains 2, the group of Zinc fingers CCCH-type|Small nucleolar RNA protein coding host genes|Ring finger proteins
Gene summary
Enables DNA binding activity; RNA binding activity; and ubiquitin protein ligase activity. Involved in protein polyubiquitination. Located in cell surface and membrane. [provided by Alliance of Genome Resources, Jun 2026]
- MNAB
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~60.8 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 RC3H2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001100588.3. 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 | 1 | 3 | |||
| missense | 121 | 121 | ||||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 10 | 10 | ||||
| Total | 0 | 0 | 136 | 1 | 0 | 137 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001094058.1 | 20 | MANE Select | |
| Ensembl | ENSP00000349783.2 | 20 | MANE Select | |
| RefSeq | NP_001341407.1 | 20 | Standard | |
| RefSeq | NP_001341408.1 | 19 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- protein polyubiquitination
- B cell homeostasis
- regulation of transcription by RNA polymerase II
- post-embryonic development
- posttranscriptional regulation of gene expression
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA binding
- RNA binding
- double-stranded RNA binding
- mRNA binding
Cellular Component
- P-body
- cell surface
- membrane
- intracellular membrane-bounded organelle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000373670
- Coding exons
- 20
- Length
- 60786
- Individuals with no LoFs
- 124789
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 10
- Defined
- 124799
- p
- 0.0000401
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.45 | 463 | 637 | 0.727 | 0.0000328 | 7761 |
| Missense (PolyPhen) | 233 | 362.9 | 0.64205 | 4485 | ||
| Synonymous | 0.645 | 217 | 229 | 0.946 | 0.0000121 | 2375 |
| Loss of Function | 6.72 | 5 | 62.2 | 0.0803 | 0.00000354 | 706 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000065 | 0.000065 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000056 | 0.000056 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000063 | 0.000062 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Post-transcriptional repressor of mRNAs containing a conserved stem loop motif, called constitutive decay element (CDE), which is often located in the 3'-UTR, as in HMGXB3, ICOS, IER3, NFKBID, NFKBIZ, PPP1R10, TNF and in many more mRNAs. Binds to CDE and promotes mRNA deadenylation and degradation. This process does not involve miRNAs. In follicular helper T (Tfh) cells, represses of ICOS and TNFRSF4 expression, thus preventing spontaneous Tfh cell differentiation, germinal center B-cell differentiation in the absence of immunization and autoimmunity. In resting or LPS-stimulated macrophages, controls inflammation by suppressing TNF expression. Also recognizes CDE in its own mRNA and in that of paralogous RC3H1, possibly leading to feedback loop regulation (By similarity). miRNA-binding protein that regulates microRNA homeostasis. Enhances DICER-mediated processing of pre- MIR146a but reduces mature MIR146a levels through an increase of 3' end uridylation. Both inhibits ICOS mRNA expression and they may act together to exert the suppression (PubMed:25697406). Acts as a ubiquitin E3 ligase. Pairs with E2 enzymes UBE2B, UBE2D2, UBE2E2, UBE2E3, UBE2G2, UBE2K and UBE2Q2 and produces polyubiquitin chains (PubMed:26489670). Show the strongest activity when paired with UBE2N:UBE2V1 or UBE2N:UBE2V2 E2 complexes and generate both short and long polyubiquitin chains (PubMed:26489670). Involved in the ubiquitination of MAP3K5 (PubMed:24448648, PubMed:26489670) (By similarity). Able to interact with double-stranded RNA (dsRNA) (PubMed:26489670). {ECO:0000250|UniProtKB:P0C090, ECO:0000269|PubMed:24448648, ECO:0000269|PubMed:26489670}.;
Intolerance Scores
- LoFtool
- 0.0705
- RVIS EVS
- -1.33
- RVIS percentile EVS
- 4.69
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.974
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |