PJA2
protein-codingpraja ring finger ubiquitin ligase 2, the group of Ring finger proteins
Gene summary
Enables cAMP-dependent protein kinase inhibitor activity and ubiquitin protein ligase activity. Involved in several processes, including positive regulation of signal transduction; proteasome-mediated ubiquitin-dependent protein catabolic process; and regulation of macrophage activation. Located in centriolar satellite; cytosol; and plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]
- RNF131
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~75.3 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 PJA2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014819.5. 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 | 96 | 2 | 98 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 102 | 2 | 0 | 104 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055634.3 | 9 | MANE Select | |
| Ensembl | ENSP00000354775.2 | 9 | MANE Select | |
| Ensembl | ENSP00000355284.3 | 9 | Standard | |
| Ensembl | ENSP00000355284.3 | 9 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| pja2 | Danio rerio | Structure: post-vent region Quality: deformed abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Immune System
- Adaptive Immune System
- Antigen processing: Ubiquitination & Proteasome degradation
- Class I MHC mediated antigen processing & presentation
Biological Process
- inflammatory response
- long-term memory
- regulation of protein kinase A signaling
- protein ubiquitination
- positive regulation of toll-like receptor 2 signaling pathway
Molecular Function
- ubiquitin-protein transferase activity
- protein binding
- protein kinase A catalytic subunit binding
- protein kinase A regulatory subunit binding
- metal ion binding
Cellular Component
- Golgi membrane
- cytoplasm
- endoplasmic reticulum membrane
- plasma membrane
- postsynaptic density
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000361189
- Coding exons
- 9
- Length
- 75286
- Individuals with no LoFs
- 125729
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 15
- Defined
- 125744
- p
- 0.0000596
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.426 | 339 | 362 | 0.937 | 0.0000165 | 4709 |
| Missense (PolyPhen) | 38 | 87.29 | 0.43533 | 1193 | ||
| Synonymous | -0.982 | 138 | 124 | 1.11 | 0.00000568 | 1274 |
| Loss of Function | 3.69 | 9 | 31.3 | 0.288 | 0.00000139 | 410 |
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 | 0.0 | absent |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000036 | 0.000035 | rare |
| South Asian | 0.00017 | 0.00016 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Has E2-dependent E3 ubiquitin-protein ligase activity. Responsible for ubiquitination of cAMP-dependent protein kinase type I and type II-alpha/beta regulatory subunits and for targeting them for proteasomal degradation. Essential for PKA- mediated long-term memory processes. Through the ubiquitination of MFHAS1, positively regulates the TLR2 signaling pathway that leads to the activation of the downstream p38 and JNK MAP kinases and promotes the polarization of macrophages toward the pro- inflammatory M1 phenotype (PubMed:28471450). {ECO:0000269|PubMed:12036302, ECO:0000269|PubMed:21423175, ECO:0000269|PubMed:28471450}.;
Recessive Scores
- pRec
- 0.0951
Intolerance Scores
- LoFtool
- 0.489
- RVIS EVS
- -0.13
- RVIS percentile EVS
- 43.98
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.940
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |