LHPP
protein-codingphospholysine phosphohistidine inorganic pyrophosphate phosphatase, the group of HAD Asp-based non-protein phosphatases|Haloacid dehalogenase like hydrolase domain containing
Gene summary
Enables inorganic diphosphate phosphatase activity and protein homodimerization activity. Involved in phosphate-containing compound metabolic process. Located in cytosol and nuclear speck. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~156.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to LHPP variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_022126.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | 2 | |||
| missense | 55 | 1 | 1 | 57 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 56 | 2 | 2 | 60 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_071409.3 | 7 | MANE Select | |
| Ensembl | ENSP00000357835.5 | 7 | MANE Select | |
| RefSeq | NP_001161352.1 | 6 | Standard | |
| RefSeq | NP_001305260.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Oxidative phosphorylation - Homo sapiens (human)
- Metabolism of nucleotides
- Metabolism
- Nucleobase biosynthesis
- Purine ribonucleoside monophosphate biosynthesis
Biological Process
- protein dephosphorylation
- phosphate-containing compound metabolic process
- purine ribonucleoside monophosphate biosynthetic process
- dephosphorylation
Molecular Function
- magnesium ion binding
- inorganic diphosphatase activity
- phosphatase activity
- protein homodimerization activity
- protein histidine phosphatase activity
Cellular Component
- nucleus
- cytosol
- nuclear speck
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000368842
- Coding exons
- 7
- Length
- 156055
- Individuals with no LoFs
- 125705
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 43
- Defined
- 125748
- p
- 0.000171
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0226 | 154 | 155 | 0.995 | 0.00000983 | 1716 |
| Missense (PolyPhen) | 48 | 55.498 | 0.86489 | 630 | ||
| Synonymous | 0.0589 | 65 | 65.6 | 0.991 | 0.00000470 | 554 |
| Loss of Function | 0.291 | 11 | 12.1 | 0.910 | 5.95e-7 | 152 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00049 | 0.00049 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00033 | 0.00033 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00014 | 0.00014 | rare |
| South Asian | 0.000099 | 0.000098 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Phosphatase that hydrolyzes imidodiphosphate, 3- phosphohistidine and 6-phospholysine. Has broad substrate specificity and can also hydrolyze inorganic diphosphate, but with lower efficiency (By similarity). {ECO:0000250}.;
Intolerance Scores
- LoFtool
- 0.875
- RVIS EVS
- 0.11
- RVIS percentile EVS
- 61.91
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.865
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |