Neuropathy target esterase

PNPLA6
Identifiers
Aliases	PNPLA6, BNHS, NTE, NTEMND, SPG39, iPLA2delta, sws, LNMS, OMCS, patatin like phospholipase domain containing 6
External IDs	OMIM: 603197; MGI: 1354723; HomoloGene: 21333; GeneCards: PNPLA6; OMA:PNPLA6 - orthologs
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19p13.2 Start 7,534,004 bp[1] End 7,561,764 bp[1]
Gene location (Mouse) Chr. Chromosome 8 (mouse)[2] Band 8 A1.1|8 1.92 cM Start 3,565,384 bp[2] End 3,594,267 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in granulocyte upper lobe of left lung right frontal lobe anterior pituitary mucosa of transverse colon right lung right testis spleen left testis apex of heart Top expressed in neural layer of retina epithelium of small intestine superior frontal gyrus gastrula primary visual cortex vestibular membrane of cochlear duct right kidney lens epiblast duodenum More reference expression data BioGPS More reference expression data
Gene ontology Molecular function hydrolase activity lysophospholipase activity Cellular component integral component of membrane endoplasmic reticulum membrane endoplasmic reticulum membrane Biological process lipid catabolic process metabolism phosphatidylcholine metabolic process developmental process lipid metabolism glycerophospholipid catabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 10908 50767 Ensembl ENSG00000032444 ENSMUSG00000004565 UniProt Q8IY17 Q3TRM4 RefSeq (mRNA) NM_006702 NM_001166111 NM_001166112 NM_001166113 NM_001166114 NM_001122818 NM_015801 NM_001359121 NM_001359122 NM_001359123 NM_001359124 NM_001378951 NM_001378952 NM_001378953 NM_001378954 NM_001378955 RefSeq (protein) NP_001159583 NP_001159584 NP_001159585 NP_001159586 NP_006693 NP_001116290 NP_056616 NP_001346050 NP_001346051 NP_001346052 NP_001346053 NP_001365880 NP_001365881 NP_001365882 NP_001365883 NP_001365884 Location (UCSC) Chr 19: 7.53 – 7.56 Mb Chr 8: 3.57 – 3.59 Mb PubMed search [3] [4]
Wikidata
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Neuropathy target esterase, also known as patatin-like phospholipase domain-containing protein 6 (PNPLA6), is an esterase enzyme that in humans is encoded by the PNPLA6 gene.^[5][6][7][8]

Neuropathy target esterase is a phospholipase that deacetylates intracellular phosphatidylcholine to produce glycerophosphocholine. It is thought to function in neurite outgrowth and process elongation during neuronal differentiation. The protein is anchored to the cytoplasmic face of the endoplasmic reticulum in both neurons and non-neuronal cells.^[8]

Function

Neuropathy target esterase is an enzyme with phospholipase B activity: it sequentially hydrolyses both fatty acids from the major membrane lipid phosphatidylcholine, generating water-soluble glycerophosphocholine.^[9][10] In eukaryotic cells, NTE is anchored to the cytoplasmic face of the endoplasmic reticulum membrane. In mammals, it is particularly abundant in neurons, the placenta, and the kidney.^{[11][12][13][14][15]} Loss of NTE activity results in abnormally-elevated levels of phosphatidylcholine in the brain and impairment of the constitutive secretory pathway in neurons.^[5][16][17]

In the kidney, the expression of neuropathy target esterase is regulated by TonEBP as part of osmolyte production when the kidney produces concentrated urine.^[18]

Clinical significance

Mutations in this gene result in autosomal-recessive spastic paraplegia. The protein is also the target for neurodegeneration induced by organophosphorus compounds and chemical warfare agents.^[8]

Recessively-inherited mutations in NTE that substantially reduce its catalytic activity cause a rare form of hereditary spastic paraplegia (SPG39), in which distal parts of long spinal axons degenerate leading to limb weakness and paralysis.^[19][20] Organophosphate-induced delayed neuropathy— a paralysing syndrome with distal degeneration of long axons— results from poisoning with neuropathic organophosphorus compounds that irreversibly inhibit NTE.^{[21][22][23][24][25][26]}

References

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.