PNPLA8 (patatin like domain 8, phospholipase A2)

Gene

• Entrez ID: 50640
• Gene name: Patatin like domain 8, phospholipase A2
• Gene symbol: PNPLA8
• Synonyms (NCBI Gene): IPLA2-2, IPLA2G, MMLA, PNPLA-gamma, iPLA2gamma
• Chromosome: 7
• Chromosome location: 7q31.1
• Summary: This gene encodes a member of the patatin-like phospholipase domain containing protein family. Members of this family are phospholipases which catalyze the cleavage of fatty acids from membrane phospholipids. The product of this gene is a calcium-independ

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs774184465	AG>-	Uncertain-significance, pathogenic	Coding sequence variant, downstream transcript variant, genic downstream transcript variant, non coding transcript variant, frameshift variant
rs786205882	TAAT>-	Pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant
rs1598909288	C>T	Likely-pathogenic	Stop gained, coding sequence variant, non coding transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT020888	hsa-miR-155-5p	Proteomics	18668040
MIRT439939	hsa-miR-218-5p	HITS-CLIP	23212916
MIRT439939	hsa-miR-218-5p	HITS-CLIP	23212916
MIRT1245503	hsa-miR-1270	CLIP-seq
MIRT1245504	hsa-miR-203	CLIP-seq
MIRT1245505	hsa-miR-2682	CLIP-seq
MIRT1245506	hsa-miR-3127-5p	CLIP-seq
MIRT1245507	hsa-miR-3174	CLIP-seq
MIRT1245508	hsa-miR-331-5p	CLIP-seq
MIRT1245509	hsa-miR-338-5p	CLIP-seq
MIRT1245510	hsa-miR-34a	CLIP-seq
MIRT1245511	hsa-miR-34c-5p	CLIP-seq
MIRT1245512	hsa-miR-3591-3p	CLIP-seq
MIRT1245513	hsa-miR-3653	CLIP-seq
MIRT1245514	hsa-miR-3658	CLIP-seq
MIRT1245515	hsa-miR-3691-5p	CLIP-seq
MIRT1245516	hsa-miR-3714	CLIP-seq
MIRT1245517	hsa-miR-375	CLIP-seq
MIRT1245518	hsa-miR-3911	CLIP-seq
MIRT1245519	hsa-miR-410	CLIP-seq
MIRT1245520	hsa-miR-421	CLIP-seq
MIRT1245521	hsa-miR-4272	CLIP-seq
MIRT1245522	hsa-miR-4302	CLIP-seq
MIRT1245523	hsa-miR-4434	CLIP-seq
MIRT1245524	hsa-miR-4495	CLIP-seq
MIRT1245525	hsa-miR-449a	CLIP-seq
MIRT1245526	hsa-miR-449b	CLIP-seq
MIRT1245527	hsa-miR-449c	CLIP-seq
MIRT1245528	hsa-miR-4516	CLIP-seq
MIRT1245529	hsa-miR-4531	CLIP-seq
MIRT1245530	hsa-miR-4635	CLIP-seq
MIRT1245531	hsa-miR-4752	CLIP-seq
MIRT1245532	hsa-miR-513a-3p	CLIP-seq
MIRT1245533	hsa-miR-548an	CLIP-seq
MIRT1245534	hsa-miR-548t	CLIP-seq
MIRT1245535	hsa-miR-578	CLIP-seq
MIRT1245536	hsa-miR-580	CLIP-seq
MIRT1245537	hsa-miR-607	CLIP-seq
MIRT1245538	hsa-miR-620	CLIP-seq
MIRT1245539	hsa-miR-656	CLIP-seq
MIRT1245540	hsa-miR-921	CLIP-seq
MIRT2299851	hsa-miR-4668-3p	CLIP-seq
MIRT2432206	hsa-miR-320a	CLIP-seq
MIRT2432207	hsa-miR-320b	CLIP-seq
MIRT2432208	hsa-miR-320c	CLIP-seq
MIRT2432209	hsa-miR-320d	CLIP-seq
MIRT2432210	hsa-miR-4429	CLIP-seq
MIRT2432211	hsa-miR-944	CLIP-seq
MIRT2596529	hsa-miR-127-5p	CLIP-seq
MIRT2596530	hsa-miR-3143	CLIP-seq
MIRT2432206	hsa-miR-320a	CLIP-seq
MIRT2432207	hsa-miR-320b	CLIP-seq
MIRT2432208	hsa-miR-320c	CLIP-seq
MIRT2432209	hsa-miR-320d	CLIP-seq
MIRT2596531	hsa-miR-320e	CLIP-seq
MIRT2596532	hsa-miR-3607-3p	CLIP-seq
MIRT2596533	hsa-miR-3686	CLIP-seq
MIRT2596534	hsa-miR-412	CLIP-seq
MIRT2596535	hsa-miR-4320	CLIP-seq
MIRT2432210	hsa-miR-4429	CLIP-seq
MIRT2596536	hsa-miR-4452	CLIP-seq
MIRT2596537	hsa-miR-4477a	CLIP-seq
MIRT2596538	hsa-miR-4778-5p	CLIP-seq
MIRT2596539	hsa-miR-563	CLIP-seq
MIRT2432211	hsa-miR-944	CLIP-seq
MIRT2596530	hsa-miR-3143	CLIP-seq
MIRT2432206	hsa-miR-320a	CLIP-seq
MIRT2432207	hsa-miR-320b	CLIP-seq
MIRT2432208	hsa-miR-320c	CLIP-seq
MIRT2432209	hsa-miR-320d	CLIP-seq
MIRT2596531	hsa-miR-320e	CLIP-seq
MIRT2596532	hsa-miR-3607-3p	CLIP-seq
MIRT2596533	hsa-miR-3686	CLIP-seq
MIRT2596534	hsa-miR-412	CLIP-seq
MIRT2432210	hsa-miR-4429	CLIP-seq
MIRT2596536	hsa-miR-4452	CLIP-seq
MIRT2596537	hsa-miR-4477a	CLIP-seq
MIRT2596538	hsa-miR-4778-5p	CLIP-seq
MIRT2432211	hsa-miR-944	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001516	Process	Prostaglandin biosynthetic process	IDA	15695510
GO:0004620	Function	Phospholipase activity	IEA
GO:0004622	Function	Phosphatidylcholine lysophospholipase activity	IEA
GO:0004623	Function	Phospholipase A2 activity	IEA
GO:0005524	Function	ATP binding	NAS	10744668
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IEA
GO:0005739	Component	Mitochondrion	ISS
GO:0005777	Component	Peroxisome	IDA	15695510
GO:0005777	Component	Peroxisome	IEA
GO:0005778	Component	Peroxisomal membrane	IDA	10744668
GO:0005778	Component	Peroxisomal membrane	IEA
GO:0005783	Component	Endoplasmic reticulum	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	TAS
GO:0006629	Process	Lipid metabolic process	IEA
GO:0006631	Process	Fatty acid metabolic process	IDA	10744668
GO:0008970	Function	Phospholipase A1 activity	IEA
GO:0016020	Component	Membrane	IBA
GO:0016020	Component	Membrane	IDA	10833412, 18171998
GO:0016020	Component	Membrane	IEA
GO:0016042	Process	Lipid catabolic process	IEA
GO:0016787	Function	Hydrolase activity	IEA
GO:0019369	Process	Arachidonate metabolic process	IBA
GO:0019369	Process	Arachidonate metabolic process	IDA	10833412, 15695510, 28442572
GO:0031966	Component	Mitochondrial membrane	IEA
GO:0032048	Process	Cardiolipin metabolic process	IDA	28442572
GO:0032048	Process	Cardiolipin metabolic process	IEA
GO:0034638	Process	Phosphatidylcholine catabolic process	IDA	15695510
GO:0035556	Process	Intracellular signal transduction	IDA	15695510
GO:0043651	Process	Linoleic acid metabolic process	IDA	15695510
GO:0046338	Process	Phosphatidylethanolamine catabolic process	IDA	15695510
GO:0047499	Function	Calcium-independent phospholipase A2 activity	IBA
GO:0047499	Function	Calcium-independent phospholipase A2 activity	IDA	10744668, 10833412, 15695510, 15908428, 18171998
GO:0047499	Function	Calcium-independent phospholipase A2 activity	IEA
GO:0047499	Function	Calcium-independent phospholipase A2 activity	IMP	28442572
GO:0050482	Process	Arachidonate secretion	IDA	10833412, 15695510
GO:0055088	Process	Lipid homeostasis	IEA
GO:0055088	Process	Lipid homeostasis	IMP	17213206
GO:0070328	Process	Triglyceride homeostasis	IEA
GO:0070328	Process	Triglyceride homeostasis	IMP	17213206
GO:1900407	Process	Regulation of cellular response to oxidative stress	IEA

Other IDs

• MIM: 612123
• HGNC: 28900
• e!Ensembl: ENSG00000135241

Protein

• UniProt ID: Q9NP80
• Protein name: Calcium-independent phospholipase A2-gamma (EC 3.1.1.-) (EC 3.1.1.5) (Intracellular membrane-associated calcium-independent phospholipase A2 gamma) (iPLA2-gamma) (PNPLA-gamma) (Patatin-like phospholipase domain-containing protein 8) (iPLA2-2)
• Protein function: Calcium-independent and membrane-bound phospholipase, that catalyzes the esterolytic cleavage of fatty acids from glycerophospholipids to yield free fatty acids and lysophospholipids, hence regulating membrane physical properties and the release
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01734	Patatin	445 → 640	Patatin-like phospholipase	Family

• Tissue specificity: TISSUE SPECIFICITY: Expressed in parenchymal tissues including heart, skeletal muscle, placenta, brain, liver and pancreas. Also expressed in bronchial epithelial cells and kidney. Highest expression is observed in skeletal muscle and heart. {ECO:0000269|
• Sequence:

  MSINLTVDIYIYLLSNARSVCGKQRSKQLYFLFSPKHYWRISHISLQRGFHTNIIRCKWT
  KSEAHSCSKHCYSPSNHGLHIGILKLSTSAPKGLTKVNICMSRIKSTLNSVSKAVFGNQN
  EMISRLAQFKPSSQILRKVSDSGWLKQKNIKQAIKSLKKYSDKSAEKSPFPEEKSHIIDK
  EEDIGKRSLFHYTSSITTKFGDSFYFLSNHINSYFKRKEKMSQQKENEHFRDKSELEDKK
  VEEGKLRSPDPGILAYKPGSESVHTVDKPTSPSAIPDVLQVSTKQSIANFLSRPTEGVQA
  LVGGYIGGLVPKLKYDSKSQSEEQEEPAKTDQAVSKDRNAEEKKRLSLQREKIIARVSID
  NRTRALVQALRRTTDPKLCITRVEELTFHLLEFPEGKGVAVKERIIPYLLRLRQIKDETL
  QAAVREILALIGYVDPVKGRGIRILSIDGGGTRGVVALQTLRKLVELTQKPVHQLFDYIC
  GVSTGAILAFMLGLFHMPLDECEELYRKLGSDVFSQNVIVGTVKMSWSHAFYDSQTWENI
  LKDRMGSALMIETARNPTCPKVAAVSTIVNRGITPKAFVFRNYGHFPGINSHYLGGCQYK
  MWQAIRASSAAPGYFAEYALGNDLHQDGGLLLNNPSALAMHECKCLWPDVPLECIVSLGT
  GRYESDVRNTVTYTSLKTKLSNVINSATDTEEVHIMLDGLLPPDTYFRFNPVMCENIPLD
  ESRNEKLDQLQLEGLKYIERNEQKMKKVAKILSQEKTTLQKINDWIKLKTDMYEGLPFFS
  KL

• Sequence length: 782

Pathways

Reactome:

Acyl chain remodelling of PC
Acyl chain remodelling of PE

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Abnormality of the musculature	Likely pathogenic	rs770314806	RCV001814422	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Mitochondrial myopathy-lactic acidosis-deafness syndrome	Likely pathogenic; Pathogenic	rs2154516696, rs2154515356, rs1462456361, rs786205882, rs774184465, rs1444737333, rs753758872, rs1861563628, rs1248710641, rs2552112201, rs1598909288	RCV001358689 RCV001795819 RCV001806370 RCV000170361 RCV000170362 RCV003148381 RCV003331723 RCV003335977 RCV005603855 RCV003989351 RCV000991386	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
PNPLA8-related disorder	Likely pathogenic	rs2552117876	RCV003416878	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Colorectal cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Complex neurodevelopmental disorder	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonpapillary renal cell carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OLIGODENDROGLIOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OVARIAN SEROUS CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acidosis Lactic	Lactic acidosis	Pubtator	29681094	Associate	★☆☆☆☆ Found in Text Mining only
Adenocarcinoma	Adenocarcinoma	BEFREE	15695510		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	38017485	Stimulate	★☆☆☆☆ Found in Text Mining only
Cerebellar atrophy	Cerebellar atrophy	BEFREE	29681094		★☆☆☆☆ Found in Text Mining only
Cerebellar Diseases	Cerebellar diseases	Pubtator	29681094	Associate	★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	15695510		★☆☆☆☆ Found in Text Mining only
Complex partial seizure with impairment of consciousness	Dyscognitive seizures	HPO_DG			★☆☆☆☆ Found in Text Mining only
Complex partial seizures	Seizure	HPO_DG			★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Developmental disability	Pubtator	29681094	Associate	★☆☆☆☆ Found in Text Mining only
Dysarthria	Dysarthria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Heart Diseases	Heart disease	Pubtator	29305524	Associate	★☆☆☆☆ Found in Text Mining only
Heart Failure	Heart failure	Pubtator	29305524	Associate	★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	Pubtator	29681094	Associate	★☆☆☆☆ Found in Text Mining only
Mitochondrial Diseases	Mitochondrial Diseases	BEFREE	29681094		★☆☆☆☆ Found in Text Mining only
Mitochondrial Diseases	Mitochondrial disease	Pubtator	29681094	Associate	★☆☆☆☆ Found in Text Mining only
Mitochondrial Myopathies	Mitochondrial myopathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Mitochondrial myopathy with lactic acidosis	Mitochondrial myopathy-lactic acidosis-deafness syndrome	GENOMICS_ENGLAND_DG	25473036, 29681094		★☆☆☆☆ Found in Text Mining only
Mitochondrial myopathy with lactic acidosis	Mitochondrial myopathy-lactic acidosis-deafness syndrome	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Mitochondrial myopathy with lactic acidosis	Mitochondrial myopathy-lactic acidosis-deafness syndrome	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Necrosis	Necrosis	Pubtator	29305524	Associate	★☆☆☆☆ Found in Text Mining only
Neurodegenerative Diseases	Neurodegenerative disorder	Pubtator	29681094	Associate	★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	Pubtator	18445270	Associate	★☆☆☆☆ Found in Text Mining only
Triple Negative Breast Neoplasms	Triple negative breast cancer	Pubtator	38017485	Stimulate	★☆☆☆☆ Found in Text Mining only