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FLASH GENE

Symbol

PNPLA3

contributors: mct/npt/pgu - updated : 10-06-2011

HGNC name	patatin-like phospholipase domain containing 3
HGNC id	18590

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	23.83 kb     9 Exon(s)

regulatory sequence	Promoter
text structure	MLXIPL has been identified as a transcription factor regulating the induction of liver pyruvate kinase and other lipogenic genes in response to a high carbohydrate diet and it was possible that it might also contribute to the glucose-responsiveness of PNPLA3 (

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_025225 9 - 2805 52.7 481 - 2008 19029121

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive intestine large intestine colon       liver       highly Homo sapiens Nervous brain         Skin/Tegument skin         Urinary kidney         Visual eye

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose     highly Homo sapiens Muscular striatum skeletal

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

a shared protein domain discovered initially in patatin

HOMOLOGY

interspecies	homolog to Drosophila CG5560
	homolog to C.elegans C05D11.7a

Homologene

FAMILY	IPLA2/lipase family
	patatin-like phospholipase family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	plasma membrane
text	strongly associated with membranes and with lipid droplets

basic FUNCTION	triacylglycerol lipase that mediates triacylglycerol hydrolysis in adipocytes
	may be involved in the balance of energy usage/storage in adipocytes
	participating in triacylglycerol hydrolysis and the acyl-CoA independent transacylation of acylglycerols, thereby facilitating energy mobilization and storage in adipocytes
	lipid hydrolase with an unusual folding topology that differs from classical lipases
	role for adiponutrin as a susceptibility gene for hepatic dysfunction
	its function may be related to some regulatory aspect of the pathway of lipogenesis or lipolysis
	plays a role in the hydrolysis of glycerolipids (

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein

interacting with USF2 (USF2 is one of the transcription factors that can regulate adiponutrin promoter activity in the presence of glucose)

cell & other

REGULATION

Other	highly regulated by changes in energy balance
	nutritionally regulated, decreasing after fasting and strongly up-regulated by feeding in adipose tissue and liver
	regulated in a coordinated manner with genes involved in lipogenesis

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --low   by fasting in adipose tissue constitutional     --over   in adipose tissue and in liver of obese patients constitutional germinal mutation     loss of function I148M substitution causes a loss of function in nonalcoholic fatty liver disease

Susceptibility

to nonalcoholic fatty liver disease to obesity to alcoholic liver disease and clinically evident alcoholic cirrhosis to lower HDL cholesterol and a tendency toward lower free fatty acid levels to hepatic steatosis in obese youths to non-alcoholic fatty liver disease

Variant & Polymorphism SNP , other	variant (rs738409) was strongly associated with hepatic fat content and nonalcoholic fatty liver disease
	rs738409 variant associated with obesity
	rs738409 in PNPLA3 is strongly associated with alcoholic liver disease and clinically evident alcoholic cirrhosis
	GG genotype had significantly lower HDL cholesterol and a tendency toward lower free fatty acid levels
	common variant of the PNPLA3 gene confers susceptibility to hepatic steatosis in obese youths without increasing the level of hepatic and peripheral insulin resistance
	PNPLA3 p.I148M variants represent genetic risk factors for non-alcoholic fatty liver disease (NAFLD)

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed obesity     potential target for therapies to manage obesity and its associated disorders by controlling its expression or actions

ANIMAL & CELL MODELS