PHPT1
Chr 9phosphohistidine phosphatase 1
Also known as: CGI-202, HEL-S-132P, HSPC141, PHP, PHP14
This enzyme catalyzes the dephosphorylation of histidine residues in proteins, including G-beta subunits and ATP citrate lyase, and regulates CD4 T lymphocytes through KCa3.1 channel modulation. Mutations cause autosomal recessive neurodegeneration with brain iron accumulation (NBIA), typically presenting with progressive movement disorders, cognitive decline, and characteristic brain iron deposition on MRI. The gene is extremely tolerant to loss-of-function variants (pLI near 0), suggesting the recessive inheritance pattern aligns with the gene's constraint profile.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
ClinVar Variant Classifications
130 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
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 | |||
| Total | 0 | 34 | 87 | 1 | 124 |
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.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools