PSPH

Chr 7

phosphoserine phosphatase

Also known as: PSP, PSPHD

NCBI Gene: 5723 ENSG00000146733 UniProt: P78330

The protein encoded by this gene belongs to a subfamily of the phosphotransferases. This encoded enzyme is responsible for the third and last step in L-serine formation. It catalyzes magnesium-dependent hydrolysis of L-phosphoserine and is also involved in an exchange reaction between L-serine and L-phosphoserine. Deficiency of this protein is thought to be linked to Williams syndrome. [provided by RefSeq, Jul 2008]

GeneReviews Research

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtPhosphoserine phosphatase deficiency

Clinical highlights

Gene–disease validity (ClinGen)

Moderate · neurometabolic disorder due to serine deficiency · AR · ClinGen 2024

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.19

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — PSPH

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.19LOEUF

pLI 0.001

Z-score 1.16

OE 0.60 (0.33–1.19)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.78Z-score

OE missense 0.80 (0.68–0.95)

101 obs / 125.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.60 (0.33–1.19)

0≤0.351.4

Missense OE?0.80 (0.68–0.95)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 6 / 10.0Missense obs/exp: 101 / 125.5Syn Z: 0.35

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 100

239 rare PASS variants

Rare truncating (LoF)

1 in 2,900

34 rare PASS variants

Rare synonymous (reference)

1 in 760

79 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PSPH. 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)	~556k	1 in 210	1 in 13,000
South Asian	~43k	1 in 360	1 in 6,200
Remaining (unassigned)	~30k	1 in 200	1 in 920
European (Finnish)	~27k	1 in 490	1 in 700
Admixed American	~22k	1 in 170	1 in 2,800
African / African American	~21k	1 in 330	1 in 2,000
East Asian	~20k	1 in 220	≈ 1 in 6,600
Ashkenazi Jewish	~13k	1 in 620	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 220	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 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓