PHPT1

Chr 9

phosphohistidine phosphatase 1

Also known as: CGI-202, HEL-S-132P, HSPC141, PHP, PHP14

NCBI Gene: 29085ENSG00000054148UniProt: Q9NRX4

This gene encodes an enzyme that catalyzes the reversible dephosphorylation of histidine residues in proteins. It may be involved in the dephosphorylation of G-beta and ATP citrate lyase and in negatively regulating CD4 T lymphocytes by dephosphorylation and inhibition of KCa3.1 channels. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

0
Active trials
78
Pathogenic / LP
124
ClinVar variants
2
Pubs (1 yr)
-0.4
Missense Z
1.84
LOEUF
Clinical Summary— PHPT1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
78 Pathogenic / Likely Pathogenic· 37 VUS of 124 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.84LOEUF
pLI 0.000
Z-score -0.22
OE 1.10 (0.59–1.84)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.35Z-score
OE missense 1.11 (0.94–1.32)
91 obs / 82.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.10 (0.59–1.84)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.11 (0.94–1.32)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.52
0≤1.21.6
LoF obs/exp: 6 / 5.5Missense obs/exp: 91 / 82.0Syn Z: -2.49

ClinVar Variant Classifications

124 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic74
Likely Pathogenic4
VUS37
Likely Benign4
Benign3
Conflicting2
74
Pathogenic
4
Likely Pathogenic
37
VUS
4
Likely Benign
3
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
74
0
74
Likely Pathogenic
0
0
4
0
4
VUS
0
30
7
0
37
Likely Benign
0
3
0
1
4
Benign
0
1
2
0
3
Conflicting
—2
Total034871124

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

View in ClinVar →

Protein Context — Lollipop Plot

PHPT1 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 3 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients