PNPLA5

Summary

PNPLA5 (patatin like domain 5, triacylglycerol lipase , HGNC:24888) is a protein-coding gene on chromosome 22q13.31, encoding Patatin-like phospholipase domain-containing protein 5 (Q7Z6Z6). Has abundant triacylglycerol lipase activity.

This gene is a member of the patatin-like phospholipase family; its encoded protein has been shown to inhibit transacylation. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 150379 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 90 total
• MANE Select transcript: NM_138814

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24888
Approved symbol	PNPLA5
Name	patatin like domain 5, triacylglycerol lipase
Location	22q13.31
Locus type	gene with protein product
Status	Approved
Aliases	dJ388M5.4, GS2L
Ensembl gene	ENSG00000100341
Ensembl biotype	protein_coding
OMIM	611589
Entrez	150379

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000216177, ENST00000381198, ENST00000438734, ENST00000940358, ENST00000940359, ENST00000940360, ENST00000940361

RefSeq mRNA: 3 — MANE Select: NM_138814 NM_001177675, NM_001371410, NM_138814

CCDS: CCDS14053, CCDS54537

Canonical transcript exons

ENST00000216177 — 9 exons

Exon	Start	End
ENSE00000656920	43881558	43881674
ENSE00000656922	43886303	43886488
ENSE00000656923	43887591	43887651
ENSE00000656924	43889329	43889538
ENSE00000656925	43889799	43889864
ENSE00000656926	43891062	43891294
ENSE00001854111	43891688	43892013
ENSE00001888510	43879678	43880885
ENSE00003788161	43884213	43884345

Expression profiles

Bgee: expression breadth broad, 53 present calls, max score 74.97.

Top tissues by expression

233 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
tibialis anterior	UBERON:0001385	74.97	silver quality
pancreatic ductal cell	CL:0002079	73.76	silver quality
epithelial cell of pancreas	CL:0000083	69.05	gold quality
nucleus accumbens	UBERON:0001882	64.53	gold quality
ileal mucosa	UBERON:0000331	64.31	gold quality
upper arm skin	UBERON:0004263	63.83	gold quality
prefrontal cortex	UBERON:0000451	63.26	gold quality
putamen	UBERON:0001874	62.84	gold quality
deltoid	UBERON:0001476	61.64	silver quality
caudate nucleus	UBERON:0001873	61.20	gold quality
gingival epithelium	UBERON:0001949	60.94	gold quality
esophagus squamous epithelium	UBERON:0006920	60.09	gold quality
Brodmann (1909) area 9	UBERON:0013540	59.73	gold quality
right frontal lobe	UBERON:0002810	59.16	gold quality
upper leg skin	UBERON:0004262	59.04	gold quality
frontal cortex	UBERON:0001870	58.02	gold quality
skin of abdomen	UBERON:0001416	57.49	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	57.42	gold quality
anterior cingulate cortex	UBERON:0009835	56.97	gold quality
neocortex	UBERON:0001950	56.92	gold quality
trabecular bone tissue	UBERON:0002483	55.90	gold quality
myocardium	UBERON:0002349	55.81	gold quality
parotid gland	UBERON:0001831	55.74	gold quality
mammalian vulva	UBERON:0000997	55.33	silver quality
gingiva	UBERON:0001828	55.16	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
decidua	UBERON:0002450	54.24	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
forebrain	UBERON:0001890	53.88	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.30

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

40 targeting PNPLA5, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-1286	99.09	66.23	1046
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-4711-3P	98.97	66.87	1020
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-7113-3P	98.75	65.71	1120
HSA-MIR-6818-3P	98.56	68.23	1307

Literature-anchored findings (GeneRIF, showing 2)

• No association between genetic variants in PNPLA5 genes and childhood and adolescent obesity (PMID:19390624)
• required for optimal autophagy initiation (PMID:24613307)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pnpla5	ENSMUSG00000018868
rattus_norvegicus	Pnpla5	ENSRNOG00000022296

Paralogs (4): PNPLA4 (ENSG00000006757), PNPLA3 (ENSG00000100344), PNPLA2 (ENSG00000177666), PNPLA1 (ENSG00000180316)

Protein

Protein identifiers

Patatin-like phospholipase domain-containing protein 5 — Q7Z6Z6 (reviewed: Q7Z6Z6)

Alternative names: GS2-like protein

All UniProt accessions (2): Q7Z6Z6, B1AHL9

UniProt curated annotations — full annotation on UniProt →

Function. Has abundant triacylglycerol lipase activity.

Tissue specificity. Expressed in brain and pituitary gland.

Isoforms (2)

UniProt ID	Names	Canonical?
Q7Z6Z6-1	1	yes
Q7Z6Z6-2	2

RefSeq proteins (3): NP_001171146, NP_001358339, NP_620169* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002641	PNPLA_dom	Domain
IPR016035	Acyl_Trfase/lysoPLipase	Homologous_superfamily
IPR033562	PLPL	Family

Pfam: PF01734

Catalyzed reactions (Rhea), 1 shown:

• a triacylglycerol + H2O = a diacylglycerol + a fatty acid + H(+) (RHEA:12044)

UniProt features (12 total): sequence variant 3, short sequence motif 3, active site 2, chain 1, domain 1, sequence conflict 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z6Z6-F1	81.06	0.44

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 49 (nucleophile); 168 (proton acceptor)

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-163560	Triglyceride catabolism

MSigDB gene sets: 37 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, REACTOME_TRIGLYCERIDE_CATABOLISM, GOBP_LIPID_HOMEOSTASIS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_NEUTRAL_LIPID_CATABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_TRIGLYCERIDE_CATABOLIC_PROCESS, GOBP_NEUTRAL_LIPID_METABOLIC_PROCESS, GOBP_GLYCEROLIPID_CATABOLIC_PROCESS, GOBP_LIPID_CATABOLIC_PROCESS, DURCHDEWALD_SKIN_CARCINOGENESIS_UP, GOBP_HOMEOSTATIC_PROCESS, chr22q13, GOBP_CHEMICAL_HOMEOSTASIS, GOMF_TRIACYLGLYCEROL_LIPASE_ACTIVITY

GO Biological Process (4): triglyceride catabolic process (GO:0019433), lipid homeostasis (GO:0055088), lipid metabolic process (GO:0006629), lipid catabolic process (GO:0016042)

GO Molecular Function (4): triacylglycerol lipase activity (GO:0004806), catalytic activity (GO:0003824), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (4): cytoplasm (GO:0005737), lipid droplet (GO:0005811), cytosol (GO:0005829), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Triglyceride metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
triglyceride metabolic process	1
acylglycerol catabolic process	1
chemical homeostasis	1
primary metabolic process	1
lipid metabolic process	1
catabolic process	1
lipase activity	1
carboxylic ester hydrolase activity	1
molecular_function	1
binding	1
catalytic activity	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
cytoplasm	1

Protein interactions and networks

STRING

609 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PNPLA5	ABHD5	Q8WTS1	754
PNPLA5	PNPLA8	Q9NP80	686
PNPLA5	LDLRAP1	Q5SW96	603
PNPLA5	LIPE	Q05469	529
PNPLA5	LIPA	P38571	500
PNPLA5	PNPLA6	Q8IY17	459
PNPLA5	STAP1	Q9ULZ2	432
PNPLA5	PLIN3	O60664	418
PNPLA5	VRK1	Q99986	414
PNPLA5	PLIN1	O60240	411
PNPLA5	PLIN2	Q99541	387
PNPLA5	PNPLA7	Q6ZV29	383
PNPLA5	G0S2	P27469	382
PNPLA5	AUP1	Q9Y679	377
PNPLA5	PAFAH2	Q99487	375

IntAct

8 interactions, top by confidence:

A	B	Type	Score
PNPLA5	APPBP2	psi-mi:“MI:0915”(physical association)	0.560
PNPLA5	BAG3	psi-mi:“MI:0914”(association)	0.530
PNPLA5	HSPA8	psi-mi:“MI:0914”(association)	0.530
POF1B	PNPLA5	psi-mi:“MI:0915”(physical association)	0.400
PNPLA5	TUSC2	psi-mi:“MI:0914”(association)	0.350
PNPLA5	APPBP2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (40): UBA52 (Affinity Capture-MS), HSP90AA4P (Affinity Capture-MS), STIP1 (Affinity Capture-MS), CCT4 (Affinity Capture-MS), CCT2 (Affinity Capture-MS), HSPA8 (Affinity Capture-MS), BAG3 (Affinity Capture-MS), CCT3 (Affinity Capture-MS), PNPLA5 (Two-hybrid), PNPLA5 (Affinity Capture-MS), PNPLA5 (Affinity Capture-MS), PNPLA5 (Affinity Capture-MS), PNPLA5 (Affinity Capture-MS), PNPLA5 (Affinity Capture-MS), PNPLA5 (Affinity Capture-MS)

ESM2 similar proteins: A2ARP1, A7Z050, D3YWQ0, D3ZEY4, F1MAB7, F1S5L4, O08560, O75912, P0C548, P0C644, P16386, P49898, P54310, P97564, Q11186, Q13574, Q2KI18, Q2NKY8, Q32LZ8, Q3MJ16, Q3TRM4, Q3TZX8, Q3U1Y4, Q50L41, Q50L42, Q50L43, Q5GJ77, Q5RDF1, Q5XIL6, Q5ZI74, Q61586, Q68DD2, Q68J42, Q6IWH7, Q6NZR5, Q6P5E8, Q7Z6Z6, Q80UP3, Q80YU0, Q8BJ56

Diamond homologs: P0C548, P41247, Q11186, Q2KI18, Q32LZ8, Q3V1D5, Q7Z6Z6, Q8BJ56, Q8N8W4, Q91WW7, Q96AD5, Q9NST1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

90 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	71
Likely benign	5
Benign	13

Top pathogenic / likely-pathogenic (0)

SpliceAI

1630 predictions. Top by Δscore:

Variant	Effect	Δscore
22:43881670:CCAAC:C	acceptor_gain	1.0000
22:43881671:CAAC:C	acceptor_gain	1.0000
22:43881671:CAACC:C	acceptor_gain	1.0000
22:43881673:AC:A	acceptor_gain	1.0000
22:43881673:ACC:A	acceptor_loss	1.0000
22:43881674:CC:C	acceptor_gain	1.0000
22:43881674:CCTG:C	acceptor_loss	1.0000
22:43881675:C:CA	acceptor_loss	1.0000
22:43881676:T:A	acceptor_loss	1.0000
22:43884207:CCTTA:C	donor_loss	1.0000
22:43884208:CTTA:C	donor_loss	1.0000
22:43884209:TTA:T	donor_loss	1.0000
22:43884210:TA:T	donor_loss	1.0000
22:43884211:A:AG	donor_loss	1.0000
22:43884212:C:A	donor_loss	1.0000
22:43884212:CCTT:C	donor_gain	1.0000
22:43886344:T:TA	donor_gain	1.0000
22:43886353:TGC:T	donor_gain	1.0000
22:43886369:T:A	donor_gain	1.0000
22:43891292:AGTCT:A	acceptor_loss	1.0000
22:43891686:A:AC	donor_gain	1.0000
22:43891687:C:CC	donor_gain	1.0000
22:43891687:CCGA:C	donor_gain	1.0000
22:43881553:CTCAC:C	donor_loss	0.9900
22:43881554:TCA:T	donor_loss	0.9900
22:43881555:CA:C	donor_loss	0.9900
22:43881556:AC:A	donor_loss	0.9900
22:43881557:C:CG	donor_loss	0.9900
22:43881672:AAC:A	acceptor_gain	0.9900
22:43881675:C:CC	acceptor_gain	0.9900

AlphaMissense

2776 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:43887604:G:C	F250L	0.946
22:43887604:G:T	F250L	0.946
22:43887606:A:G	F250L	0.946
22:43891086:G:C	F134L	0.946
22:43891086:G:T	F134L	0.946
22:43891088:A:G	F134L	0.946
22:43889808:G:C	F161L	0.913
22:43889808:G:T	F161L	0.913
22:43889810:A:G	F161L	0.913
22:43891839:G:C	F14L	0.896
22:43891839:G:T	F14L	0.896
22:43891841:A:G	F14L	0.896
22:43891135:A:G	I118T	0.862
22:43889464:G:C	F189L	0.858
22:43889464:G:T	F189L	0.858
22:43889466:A:G	F189L	0.858
22:43891087:A:C	F134C	0.855
22:43891791:G:C	C30W	0.829
22:43889809:A:G	F161S	0.823
22:43891135:A:C	I118S	0.821
22:43891087:A:G	F134S	0.814
22:43891804:C:T	G26D	0.811
22:43889515:G:C	S172R	0.809
22:43889515:G:T	S172R	0.809
22:43889517:T:G	S172R	0.809
22:43887615:C:G	A247P	0.806
22:43889474:A:T	V186E	0.804
22:43884224:G:C	F357L	0.801
22:43884224:G:T	F357L	0.801
22:43884226:A:G	F357L	0.801

dbSNP variants (sampled 300 via entrez): RS1000118705 (22:43883371 C>T), RS1000467964 (22:43883581 G>A), RS1000547354 (22:43879830 C>T), RS1000572405 (22:43889296 A>G), RS1000623037 (22:43882517 A>C), RS1000831809 (22:43890421 T>C), RS1000905443 (22:43890208 A>G), RS1001429014 (22:43879895 C>T), RS1001544996 (22:43884507 C>A,T), RS1001628312 (22:43890570 T>C), RS1001764933 (22:43882326 G>A), RS1002005506 (22:43893048 G>A,C), RS1002196095 (22:43882162 G>A), RS1002479157 (22:43892836 C>T), RS1002484818 (22:43881176 G>A)

Disease associations

OMIM: gene MIM:611589 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002440_3	Staphylococcus aureus infection	7.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, decreases methylation	1
Resveratrol	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.