LIPH
protein-codinglipase H, the group of Lipases
Gene summary
This gene encodes a membrane-bound member of the mammalian triglyceride lipase family. It catalyzes the production of 2-acyl lysophosphatidic acid (LPA), which is a lipid mediator with diverse biological properties that include platelet aggregation, smooth muscle contraction, and stimulation of cell proliferation and motility. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~46.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0011452
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0011452
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0008686
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0018914
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0011452
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Dermatologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to LIPH variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_139248.3. 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 | 15 | 3 | 18 | |||
| missense | 1 | 3 | 68 | 1 | 1 | 74 |
| nonsense | 3 | 3 | ||||
| start loss | 0 | |||||
| frameshift | 2 | 4 | 1 | 7 | ||
| splice donor/acceptor (+/-2bp) | 1 | 2 | 1 | 4 | ||
| Total | 4 | 12 | 70 | 16 | 4 | 106 |
Highest pathogenic variant AF is 0.00026487617
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_640341.1 | 10 | MANE Select | |
| Ensembl | ENSP00000296252.4 | 10 | MANE Select | |
| RefSeq | NP_001424958.1 | 9 | Standard | |
| RefSeq | NP_001425580.1 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Metabolism of lipids
- Metabolism
- Glycerophospholipid biosynthesis
- Phospholipid metabolism
- Synthesis of PA
Biological Process
- phosphatidic acid biosynthetic process
- lipid catabolic process
Molecular Function
- phospholipase activity
- heparin binding
- carboxylic ester hydrolase activity
Cellular Component
- extracellular space
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000296252
- Coding exons
- 10
- Length
- 46352
- Individuals with no LoFs
- 125659
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 88
- Defined
- 125748
- p
- 0.000354
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.740 | 210 | 242 | 0.866 | 0.0000121 | 2973 |
| Missense (PolyPhen) | 79 | 86.105 | 0.91749 | 1057 | ||
| Synonymous | -0.0559 | 93 | 92.3 | 1.01 | 0.00000525 | 851 |
| Loss of Function | 0.805 | 18 | 22.1 | 0.815 | 0.00000109 | 277 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00055 | 0.00055 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00038 | 0.00033 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00035 | 0.00035 | rare |
| South Asian | 0.0010 | 0.00098 | notable |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Hydrolyzes specifically phosphatidic acid (PA) to produce 2-acyl lysophosphatidic acid (LPA; a potent bioactive lipid mediator) and fatty acid. Does not hydrolyze other phospholipids, like phosphatidylserine (PS), phosphatidylcholine (PC) and phosphatidylethanolamine (PE) or triacylglycerol (TG). {ECO:0000269|PubMed:12063250, ECO:0000269|PubMed:12963729}.;
- Disease
- DISEASE: Woolly hair autosomal recessive 2 (ARWH2) [MIM:604379]: A hair shaft disorder characterized by fine and tightly curled hair. Compared to normal curly hair that is observed in some populations, woolly hair grows slowly and stops growing after a few inches. Under light microscopy, woolly hair shows some structural anomalies, including trichorrhexis nodosa and tapered ends. Some individuals may present with hypotrichosis. {ECO:0000269|PubMed:18830268}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Intolerance Scores
- LoFtool
- 0.342
- RVIS EVS
- -0.31
- RVIS percentile EVS
- 31.93
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.208
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |