PJA2

Chr 5

praja ring finger ubiquitin ligase 2

Also known as: Neurodap1, RNF131

Enables protein kinase A catalytic subunit binding activity; protein kinase A regulatory subunit binding activity; and ubiquitin protein ligase activity. Involved in several processes, including proteasome-mediated ubiquitin-dependent protein catabolic process; regulation of macrophage activation; and regulation of signal transduction. Located in centriolar satellite; cytoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…
DNmechanismLOEUF 0.50
Clinical SummaryPJA2
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.
📋
ClinVar Variants
94 VUS of 115 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint?
0.50LOEUF
pLI 0.024
Z-score 3.69
OE 0.29 (0.170.50)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
0.43Z-score
OE missense 0.94 (0.861.02)
339 obs / 361.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.29 (0.170.50)
00.351.4
Missense OE?0.94 (0.861.02)
00.61.4
Synonymous OE?1.11
01.21.6
LoF obs/exp: 9 / 31.3Missense obs/exp: 339 / 361.8Syn Z: -0.98

This gene — mechanism propensity

DN
0.6162th %ile
GOF
0.5856th %ile
LOF
0.4332th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

115 submitted variants in ClinVar

Classification Summary

VUS94
Likely Benign2
94
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
0
94
0
0
94
Likely Benign
0
2
0
0
2
Benign
0
0
0
0
0
Total0960096

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

25 pathogenic / likely-pathogenic (of 38) ClinVar copy-number / structural variants overlap PJA2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

PJA2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →