RNF4
protein-codingring finger protein 4, the group of Ring finger proteins
Gene summary
The protein encoded by this gene contains a RING finger motif and acts as a transcription regulator. This protein has been shown to interact with, and inhibit the activity of, TRPS1, a transcription suppressor of GATA-mediated transcription. Transcription repressor ZNF278/PATZ is found to interact with this protein, and thus reduce the enhancement of androgen receptor-dependent transcription mediated by this protein. Studies of the mouse and rat counterparts suggested a role of this protein in spermatogenesis. A pseudogene of this gene is found on chromosome 1.[provided by RefSeq, Jul 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~53.6 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 RNF4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002938.5. 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 | 4 | 4 | ||||
| missense | 30 | 3 | 33 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 33 | 7 | 0 | 40 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002929.1 | 7 | MANE Select | |
| Ensembl | ENSP00000315212.8 | 7 | MANE Select | |
| RefSeq | NP_001171938.1 | 7 | Standard | |
| RefSeq | NP_001171939.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Androgen receptor signaling pathway
- HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA)
- DNA Repair
- DNA Double-Strand Break Repair
- Homology Directed Repair
Biological Process
- androgen receptor signaling pathway
- proteasome-mediated ubiquitin-dependent protein catabolic process
- positive regulation of transcription, DNA-templated
- positive regulation of transcription by RNA polymerase II
- response to arsenic-containing substance
Molecular Function
- DNA binding
- transcription coactivator activity
- ubiquitin-protein transferase activity
- protein binding
- transcription factor binding
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- PML body
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000511600
- Coding exons
- 7
- Length
- 163101
- Individuals with no LoFs
- 124589
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 124590
- p
- 0.00000401
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.07 | 83 | 115 | 0.719 | 0.00000691 | 1234 |
| Missense (PolyPhen) | 11 | 29.134 | 0.37756 | 345 | ||
| Synonymous | 0.105 | 40 | 40.9 | 0.979 | 0.00000243 | 363 |
| Loss of Function | 2.58 | 1 | 9.68 | 0.103 | 4.08e-7 | 128 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000089 | 0.0000089 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: E3 ubiquitin-protein ligase which binds polysumoylated chains covalently attached to proteins and mediates 'Lys-6'-, 'Lys-11'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitination of those substrates and their subsequent targeting to the proteasome for degradation. Regulates the degradation of several proteins including PML and the transcriptional activator PEA3. Involved in chromosome alignment and spindle assembly, it regulates the kinetochore CENPH-CENPI-CENPK complex by targeting polysumoylated CENPI to proteasomal degradation. Regulates the cellular responses to hypoxia and heat shock through degradation of respectively EPAS1 and PARP1. Alternatively, it may also bind DNA/nucleosomes and have a more direct role in the regulation of transcription for instance enhancing basal transcription and steroid receptor- mediated transcriptional activation. {ECO:0000269|PubMed:12885770, ECO:0000269|PubMed:18408734, ECO:0000269|PubMed:19307308, ECO:0000269|PubMed:20026589, ECO:0000269|PubMed:20212317, ECO:0000269|PubMed:20943951}.;
Recessive Scores
- pRec
- 0.123
Intolerance Scores
- LoFtool
- 0.167
- RVIS EVS
- 0.55
- RVIS percentile EVS
- 81.22
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- S
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.920
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |