PRPSAP2

Chr 17

phosphoribosyl pyrophosphate synthetase associated protein 2

Also known as: PAP41

The protein plays a negative regulatory role in 5-phosphoribose 1-diphosphate synthesis, a key step in purine and pyrimidine nucleotide biosynthesis. Mutations cause Arts syndrome, an X-linked disorder characterized by profound intellectual disability, early-onset sensorineural hearing loss, delayed growth, and increased susceptibility to infections. The gene shows tolerance to loss-of-function variants (pLI 0.003), which is consistent with X-linked inheritance where males are primarily affected.

OMIMResearchSummary from UniProt
DNmechanismLOEUF 0.77
Clinical SummaryPRPSAP2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.77LOEUF
pLI 0.003
Z-score 2.25
OE 0.41 (0.230.77)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
2.60Z-score
OE missense 0.50 (0.420.58)
106 obs / 212.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.41 (0.230.77)
00.351.4
Missense OE0.50 (0.420.58)
00.61.4
Synonymous OE0.95
01.21.6
LoF obs/exp: 7 / 17.0Missense obs/exp: 106 / 212.9Syn Z: 0.33
DN
0.7326th %ile
GOF
0.6248th %ile
LOF
0.3162th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PRPSAP2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found