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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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LIPH
lipase H
Chromosome 3 · 3q27.2
NCBI Gene: 200879Ensembl: ENSG00000163898.10HGNC: HGNC:18483UniProt: A2IBA6
56PubMed Papers
22Diseases
0Drugs
12Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
glycerophospholipase activityprotein bindingheparin bindingplasma membranehypotrichosis 7woolly hair, autosomal recessive 2, with or without hypotrichosishypotrichosis simplexWoolly hair
✦AI Summary

LIPH encodes lipase H, a membrane-associated phosphatidic acid-selective phospholipase A1α that specifically hydrolyzes phosphatidic acid (PA) to produce lysophosphatidic acid (LPA) and fatty acids 1. This enzyme is localized to the outer leaflet of the plasma membrane and does not hydrolyze other phospholipids. LIPH functions through the LPA/LPAR signaling axis, where the produced LPA acts as a bioactive lipid mediator 1. In hair follicles, LIPH is expressed in the outer root sheath and plays a crucial role in hair growth and development, with reduced LIPH-LPA-LPAR6 signaling leading to decreased EGFR transactivation and underdeveloped hair phenotypes 2. Loss-of-function mutations in LIPH cause autosomal recessive woolly hair/hypotrichosis (ARWH2), characterized by sparse, tightly curled hair 32. The disease shows population-specific founder mutations, including deletion of exon 4 in Russian populations and specific point mutations (c.736T>A, c.742C>A) prevalent in Japanese families 2. Beyond hair disorders, LIPH is upregulated in breast cancer and pancreatic ductal adenocarcinoma, where it promotes glycolysis, metastasis, and cancer stem cell properties through LPA/LPAR axis activation 41. Topical minoxidil shows promise as a treatment for LIPH-related hair disorders 2.

Sources cited
1
LIPH is a phosphatidic acid-selective phospholipase A1α that produces LPA from PA and activates LPA/LPAR signaling
PMID: 37990271
2
LIPH functions in hair follicles through LPA-LPAR6 signaling affecting EGFR transactivation and hair development
PMID: 33988877
3
LIPH mutations cause inherited hair loss and growth defects, with the gene expressed in hair follicles
PMID: 17095700
4
LIPH promotes breast cancer metastasis and stem cell properties
PMID: 32618099
5
LIPH is expressed in outer root sheath of hair follicles and mutations reduce protein activity
PMID: 22272275
Disease Associationsⓘ22
hypotrichosis 7Open Targets
0.74Strong
woolly hair, autosomal recessive 2, with or without hypotrichosisOpen Targets
0.73Strong
hypotrichosis simplexOpen Targets
0.62Moderate
isolated familial wooly hair disorderOpen Targets
0.38Weak
Woolly hairOpen Targets
0.38Weak
type 2 diabetes mellitusOpen Targets
0.31Weak
frozen shoulderOpen Targets
0.29Weak
genetic disorderOpen Targets
0.19Weak
ocular hypotensionOpen Targets
0.12Weak
papillary thyroid carcinomaOpen Targets
0.10Weak
ringed hair diseaseOpen Targets
0.07Suggestive
uncombable hair syndromeOpen Targets
0.07Suggestive
bipolar disorderOpen Targets
0.07Suggestive
Griscelli diseaseOpen Targets
0.07Suggestive
breast cancerOpen Targets
0.06Suggestive
Griscelli disease type 3Open Targets
0.06Suggestive
Griscelli syndrome type 3Open Targets
0.06Suggestive
pili bifurcatiOpen Targets
0.06Suggestive
neoplasmOpen Targets
0.06Suggestive
pili tortiOpen Targets
0.06Suggestive
Hypotrichosis 7UniProt
Woolly hair autosomal recessive 2UniProt
Pathogenic Variants12
NM_139248.3(LIPH):c.280_369dup (p.Lys123_Thr124insGlyLeuLeuSerValGluAspMetAsnValValValValAspTrpAsnArgGlyAlaThrThrLeuIleTyrThrHisAlaSerSerLys)Pathogenic
Woolly hair, autosomal recessive 2, with or without hypotrichosis|not provided|Hypotrichosis 7
★★☆☆2026→ Residue 123
NM_139248.3(LIPH):c.789del (p.Ser262_Cys263insTer)Pathogenic
not provided|LIPH-related disorder
★★☆☆2025→ Residue 262
NM_139248.3(LIPH):c.742C>A (p.His248Asn)Pathogenic
Woolly hair, autosomal recessive 2, with or without hypotrichosis|Hypotrichosis 7|not provided
★★☆☆2023→ Residue 248
NM_139248.3(LIPH):c.659_660del (p.Ile220fs)Pathogenic
Hypotrichosis 7|Woolly hair, autosomal recessive 2, with or without hypotrichosis|not provided|LIPH-related disorder
★★☆☆2022→ Residue 220
NM_139248.3(LIPH):c.736T>A (p.Cys246Ser)Pathogenic
Woolly hair, autosomal recessive 2, with or without hypotrichosis|Hypotrichosis simplex|Hypotrichosis 7
★★☆☆2022→ Residue 246
NM_139248.3(LIPH):c.328C>T (p.Arg110Ter)Pathogenic
not provided|Hypotrichosis 7
★★☆☆2021→ Residue 110
NM_139248.3(LIPH):c.982+1G>CLikely pathogenic
not provided
★☆☆☆2024
NM_139248.3(LIPH):c.686delinsGTAGAACCCAACCTGGCT (p.Asp229fs)Likely pathogenic
Hypotrichosis 7
★☆☆☆2023→ Residue 229
NM_139248.3(LIPH):c.263del (p.Met88fs)Likely pathogenic
Hypotrichosis 7
★☆☆☆→ Residue 88
NM_139248.3(LIPH):c.322T>C (p.Trp108Arg)Pathogenic
Woolly hair, autosomal recessive 2, with or without hypotrichosis
☆☆☆☆2011→ Residue 108
NM_139248.3(LIPH):c.886+405_1094+962delPathogenic
Woolly hair, autosomal recessive 2, with or without hypotrichosis|Hypotrichosis 7
☆☆☆☆2009
NM_139248.3(LIPH):c.346_350del (p.Ile116fs)Pathogenic
Hypotrichosis 7
☆☆☆☆2007→ Residue 116
View on ClinVar ↗
Related Genes
LIPIShared pathway100%LPAR6Protein interaction95%LPAR3Protein interaction91%POU2F3Protein interaction91%PLIN1Shared pathway50%ABHD15Shared pathway50%
Tissue Expression6 tissues
Lung
100%
Ovary
9%
Heart
5%
Liver
4%
Brain
3%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
LIPHLIPILPAR6LPAR3POU2F3PLIN1ABHD15
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q8WWY8
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.81LoF Tolerant
pLIⓘ
0.01Tolerant
Observed/Expected LoF0.53 [0.35–0.81]
RankingsWhere LIPH stands among ~20K protein-coding genes
  • #8,092of 20,598
    Most Researched56
  • #2,689of 5,498
    Most Pathogenic Variants12
  • #6,815of 17,882
    Most Constrained (LOEUF)0.81
Genes detectedLIPH
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
LIPH contributes to glycolytic phenotype in pancreatic ductal adenocarcinoma by activating LPA/LPAR axis and maintaining ALDOA stability.
PMID: 37990271
J Transl Med · 2023
1.00
2
Novel splice site mutation in the LIPH gene in a patient with autosomal recessive woolly hair/hypotrichosis: Case report and published work review.
PMID: 29464811
J Dermatol · 2018
0.90
3
LIPH promotes metastasis by enriching stem-like cells in triple-negative breast cancer.
PMID: 32618099
J Cell Mol Med · 2020
0.80
4
Human hair growth deficiency is linked to a genetic defect in the phospholipase gene LIPH.
PMID: 17095700
Science · 2006
0.70
5
Prognostic Value and Clinical Significance of LIPH in Breast Cancer.
PMID: 34754232
Int J Gen Med · 2021
0.60