PRPS2

Chr X

phosphoribosyl pyrophosphate synthetase 2

Also known as: PRSII

NCBI Gene: 5634 ENSG00000101911 UniProt: P11908 OMIM: 311860

This gene encodes phosphoribosyl pyrophosphate synthetase, which catalyzes the synthesis of phosphoribosylpyrophosphate (PRPP) essential for purine and pyrimidine nucleotide synthesis. Mutations cause X-linked intellectual disability, often with additional features affecting the nervous system. The gene is highly constrained against loss-of-function variants and follows X-linked inheritance.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a phosphoribosyl pyrophosphate synthetase that plays a central role in the synthesis of purines and pyrimidines. The encoded protein catalyzes the synthesis of 5-phosphoribosyl 1-pyrophosphate from ATP and D-ribose 5-phosphate. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.34

LOEUF· LoF intol.

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Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — X-linked: males carry a single copy

LoF Constraint?

0.34LOEUF

pLI 0.935

Z-score 2.73

OE 0.00 (0.00–0.34)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

3.05Z-score

OE missense 0.28 (0.21–0.36)

39 obs / 140.9 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.34)

0≤0.351.4

Missense OE?0.28 (0.21–0.36)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 0 / 8.7Missense obs/exp: 39 / 140.9Syn Z: 0.46

Background carrier burden — how many people carry a rare variant somewhere in PRPS2?

gnomAD v4 · ~732k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 710

135 rare PASS variants

Rare truncating (LoF)

1 in 5,800

12 rare PASS variants

Rare synonymous (reference)

1 in 530

124 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PRPS2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~561k	1 in 710	1 in 6,100
South Asian	~36k	1 in 400	none seen
Remaining (unassigned)	~31k	1 in 760	≈ 1 in 7,600
European (Finnish)	~27k	1 in 560	≈ 1 in 27,000
Admixed American	~23k	1 in 1,300	≈ 1 in 5,800
African / African American	~21k	1 in 750	≈ 1 in 6,400
East Asian	~20k	1 in 1,400	≈ 1 in 6,600
Ashkenazi Jewish	~13k	none seen	≈ 1 in 13,000
Middle Eastern	~2,758	1 in 540	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 7 coding exons well covered in gnomAD exomes and genomes.? see exons ↓