PLIN1

Summary

PLIN1 (perilipin 1, HGNC:9076) is a protein-coding gene on chromosome 15q26.1, encoding Perilipin-1 (O60240). Modulator of adipocyte lipid metabolism.

The protein encoded by this gene coats lipid storage droplets in adipocytes, thereby protecting them until they can be broken down by hormone-sensitive lipase. The encoded protein is the major cAMP-dependent protein kinase substrate in adipocytes and, when unphosphorylated, may play a role in the inhibition of lipolysis. Alternatively spliced transcript variants varying in the 5’ UTR, but encoding the same protein, have been found for this gene.

Source: NCBI Gene 5346 — RefSeq curated summary.

At a glance

• Gene–disease (curated): PLIN1-related familial partial lipodystrophy (Definitive, ClinGen)
• GWAS associations: 2
• Clinical variants (ClinVar): 171 total — 5 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 24
• Druggable target: yes — 7 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002666

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9076
Approved symbol	PLIN1
Name	perilipin 1
Location	15q26.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000166819
Ensembl biotype	protein_coding
OMIM	170290
Entrez	5346

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 11 protein_coding, 1 retained_intron

ENST00000300055, ENST00000430628, ENST00000531697, ENST00000560330, ENST00000896664, ENST00000896665, ENST00000896666, ENST00000896667, ENST00000896668, ENST00000896669, ENST00000957093, ENST00000957094

RefSeq mRNA: 2 — MANE Select: NM_002666 NM_001145311, NM_002666

CCDS: CCDS10353

Canonical transcript exons

ENST00000300055 — 9 exons

Exon	Start	End
ENSE00001106920	89666936	89667181
ENSE00001106921	89667602	89667793
ENSE00001106924	89671482	89671564
ENSE00001106925	89673210	89673414
ENSE00001106928	89669980	89670244
ENSE00001106931	89669500	89669672
ENSE00001162108	89677445	89677503
ENSE00001275373	89679251	89679367
ENSE00001932906	89664367	89665942

Expression profiles

Bgee: expression breadth ubiquitous, 194 present calls, max score 99.18.

FANTOM5 (CAGE): breadth broad, TPM avg 17.5613 / max 3933.3049, expressed in 197 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151464	7.9020	163
151465	4.2309	125
151467	2.5573	88
151463	2.0041	116
151466	0.8670	73

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
subcutaneous adipose tissue	UBERON:0002190	99.18	gold quality
adipose tissue	UBERON:0001013	99.15	gold quality
adipose tissue of abdominal region	UBERON:0007808	98.77	gold quality
omental fat pad	UBERON:0010414	98.71	gold quality
peritoneum	UBERON:0002358	98.61	gold quality
connective tissue	UBERON:0002384	97.45	gold quality
skin of hip	UBERON:0001554	97.29	gold quality
mammary duct	UBERON:0001765	96.57	gold quality
synovial joint	UBERON:0002217	95.57	gold quality
thoracic mammary gland	UBERON:0005200	95.20	gold quality
pericardium	UBERON:0002407	95.10	gold quality
mammary gland	UBERON:0001911	95.02	gold quality
breast	UBERON:0000310	94.88	gold quality
epithelium of mammary gland	UBERON:0003244	93.57	gold quality
parotid gland	UBERON:0001831	92.45	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	90.75	gold quality
right lobe of liver	UBERON:0001114	88.76	gold quality
layer of synovial tissue	UBERON:0007616	87.29	gold quality
superficial temporal artery	UBERON:0001614	87.10	gold quality
cardiac muscle of right atrium	UBERON:0003379	86.87	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.76	gold quality
tibial nerve	UBERON:0001323	86.60	gold quality
hindlimb stylopod muscle	UBERON:0004252	84.86	gold quality
left coronary artery	UBERON:0001626	84.80	gold quality
coronary artery	UBERON:0001621	84.29	gold quality
sperm	CL:0000019	82.23	silver quality
male germ cell	CL:0000015	81.52	silver quality
saliva-secreting gland	UBERON:0001044	81.43	gold quality
mucosa of stomach	UBERON:0001199	80.98	gold quality
trabecular bone tissue	UBERON:0002483	80.85	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	1614.71
E-ANND-3	no	2.89

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1, NFKB1, NR1H3, PPARA, PPARG, RELA, RORA

miRNA regulators (miRDB)

75 targeting PLIN1, 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-126-5P	100.00	72.71	3180
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-4639-5P	99.81	67.37	1028
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-2682-5P	99.73	67.38	1055
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-5689	99.50	71.26	1154
HSA-MIR-4452	99.50	68.45	1493

Literature-anchored findings (GeneRIF, showing 40)

• Perilipin could be a factor behind impaired lipolysis in insulin-resistants sconditions. (PMID:12802495)
• perilipin was elevated in obese subjects, perhaps as a compensatory mechanism to limit basal lipolysis. (PMID:15001633)
• Transcription of the human perilipin gene is stimulated by peroxisome proliferator-activated receptor-gamma (PPAR-gamma) through a DR-1 type PPRE. (PMID:15111493)
• Genetic variation at the perilipin (PLIN) locus is associated with obesity-related phenotypes in White women (PMID:15355432)
• study suggested a significant contribution of perilipin(PLIN) polymorphism 1243 to the elevated total cholesterol (TC) levels indicating that PLIN gene may be involved in human lipid metabolism (PMID:15601966)
• data support the hypothesis that the perilipin(PLIN) locus may be a significant genetic determinant for obesity risk in whites and that women are more sensitive to the genetic effects of perilipin than men (PMID:15601970)
• The association of increased obesity risk and structure of PLIN gene is studied; results support the role of the PLIN locus as an ethnically dependent modulator of obesity risk in humans. (PMID:15770500)
• We show the presence and induction of perilipin in atheroma. (PMID:15961705)
• PLIN11482A carriers were resistant to weight loss, suggesting that this polymorphism may predict outcome of BW reduction strategies based on low-energy diets. (PMID:15985482)
• Perilipin targets a novel pool of lipid droplets for lipolytic attack by hormone-sensitive lipase (PMID:16243839)
• Cooperation with other transcription factors may be differentially involved in selective transactivation of the perilipin gene by different peroxisome proliferator-activated receptor subtypes. (PMID:16567422)
• PLIN 11482G–>A/14995A–>T polymorphisms modulate the association between SFAs/carbohydrate in diet and insulin resistance in Asian women. (PMID:16732014)
• Genetic variations in the perilipin gene can affect weight gain associated with rosiglitazone treatment in patients with type 2 diabetes. (PMID:16732015)
• Results suggest that that PLIN constitutes a susceptibility locus for reduced BMD in Japanese men. (PMID:16786163)
• The rs4578621 and rs894160 polymorphisms of the perilipin gene are not major genetic determinants of obesity and type 2 diabetes-related phenotypes in a random sample of French men and women. (PMID:16836753)
• PLIN is a candidate gene for obesity risk in humans as well as a modulator of dietary response to therapies aimed to reduce body weight and decrease metabolic syndrome risk. [REVIEW] (PMID:17353663)
• Perilipin content decreased and adipophilin increased with lipoprotein lipid loading regardless of intracellular neutral lipid composition (PMID:17927964)
• negative finding that the common variants of PLIN do not have a major effect on susceptibility to stroke in a Chinese population (PMID:18174481)
• The results of these studies demonstrated that A. phagocytophilum modulates lipid metabolism by increasing PLIN mRNA levels and facilitates infection of HL-60 cells. (PMID:18201980)
• Thus, the perilipin gene expression is regulated by a transcriptional network controlling energy metabolism, substantiating the functional importance of perilipin in the maintenance of body energy balance. (PMID:18243128)
• These 2 studies suggest that the presence of the minor C and A alleles at PLIN1 and PLIN4, respectively, are associated with a lower postprandial response that may result in lower atherogenic risk for these persons (PMID:18326614)
• Central obesity may modify the associations between PLIN variations and diabetes risk in women. (PMID:18356850)
• Perilipin, which was thought to be characteristic for lipid droplets of adipocytes and steroidogenic cells, becomes de novo expressed in hepatocytes of human, mouse, and cattle liver. (PMID:18393390)
• Polymorphisms in perilipin gene (PLIN) are not associated with obesity and weight variation in people with high risk of type 2 diabetes. (PMID:18777456)
• Associations between PLIN gene polymorphisms and obesity risk have been described but this study shows that interactions with dieetary carbohydrates affect waist size. (PMID:18806092)
• The minor A allele at PLIN was associated with higher risk of metabolic syndrome at baseline (PMID:18812483)
• Mycobacterium leprae regulates ADRP/perilipin expression to facilitate the accumulation of lipids within infected macrophages for intracellular survival. (PMID:19054096)
• evidence is presented for perilipin expression in rat, mouse, and human islets of Langerhans as well as the rat clonal beta-cell line INS-1 (PMID:19299455)
• The haplotype of the minor alleles PLIN1-4, PLIN5-7 and PLIN6, was related to body-weight regulation at a lower level of body-weight in the men as well in the women; the PLIN1-4, 6, and 5-7 locus appears as a genetic influencer of obesity risk in humans. (PMID:19385027)
• K121Q, rs7566605, and rs894160 are not major contributing factors for obesity for ENPP1, INSIG2 and PLIN (PMID:19399648)
• TNFalpha decreased ATGL and HSL protein content and triglycerides (TG)-hydrolase activity but increased basal lipolysis due to a marked reduction in perilipin protein content (PMID:19695247)
• Variation in PLIN may affect glucose and lipid metabolism in women both with and without ariation in PLIN may affect glucose and lipid metabolism in women both with and without polycystic ovary syndrome. (PMID:19782423)
• a novel role for perilipin expression in adipose tissue metabolism and regulation of obesity and its metabolic complications (PMID:19797618)
• The present study aimed at comparing expression and subcellular distribution of perilipin and hormone-sensitive lipase in two abdominal adipose tissues of lean and obese women. (PMID:20017959)
• Expression patterns of perilipin and adipophilin in nonalcoholic fatty liver disease livers vary with the size of lipid droplets (PMID:20032580)
• This study found no incrased risk of obesity in Chinese Han adults with a single nucleotide polymorphism of perilipin. (PMID:20163070)
• genetic association studies in populations in US Midwest (MN, UT): When ratio of saturated fat to carbohydrate is high in diet, plasma insulin and insulin resistance are higher in women who are carriers of the minor allele in a PLIN1 SNP (rs894160). (PMID:21193293)
• Identified two heterozygous frameshift mutations in the perilipin gene (PLIN1) in three families with partial lipodystrophy, severe dyslipidemia, and insulin-resistant diabetes; findings define a novel dominant form of inherited lipodystrophy. (PMID:21345103)
• genetic association studies in obese women in Spain (gene-diet interactions): Women on reducing diet who carry 11482(G>A) A allele have lower reduction in waist circumference and greater decrease in lipid oxidation rate than non-A allele carriers. (PMID:21392418)
• Reduced mRNA and protein content of Plin and G0S2 and borderline increased ATGL protein in sc adipose tissue from poorly controlled type 2 diabetic subjects. (PMID:22535977)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	plin1	ENSDARG00000054048
mus_musculus	Plin1	ENSMUSG00000030546
rattus_norvegicus	Plin1	ENSRNOG00000015086
drosophila_melanogaster	Lsd-2	FBGN0030608

Paralogs (4): PLIN3 (ENSG00000105355), PLIN2 (ENSG00000147872), PLIN4 (ENSG00000167676), PLIN5 (ENSG00000214456)

Protein

Protein identifiers

Perilipin-1 — O60240 (reviewed: O60240)

Alternative names: Lipid droplet-associated protein

All UniProt accessions (2): O60240, H0YM16

UniProt curated annotations — full annotation on UniProt →

Function. Modulator of adipocyte lipid metabolism. Coats lipid storage droplets to protect them from breakdown by hormone-sensitive lipase (HSL). Its absence may result in leanness. Plays a role in unilocular lipid droplet formation by activating CIDEC. Their interaction promotes lipid droplet enlargement and directional net neutral lipid transfer. May modulate lipolysis and triglyceride levels.

Subunit / interactions. Interacts with ABHD5. Interacts with CIDEC. Interacts with AQP7.

Subcellular location. Endoplasmic reticulum. Lipid droplet.

Tissue specificity. Detected in adipocytes from white adipose tissue (at protein level). Detected in visceral adipose tissue and mammary gland.

Post-translational modifications. Major cAMP-dependent protein kinase-substrate in adipocytes, also dephosphorylated by PP1. When phosphorylated, may be maximally sensitive to HSL and when unphosphorylated, may play a role in the inhibition of lipolysis, by acting as a barrier in lipid droplet.

Disease relevance. Lipodystrophy, familial partial, 4 (FPLD4) [MIM:613877] An autosomal dominant form of lipodystrophy characterized by loss of subcutaneous adipose tissue primarily affecting the lower limbs, insulin-resistant diabetes mellitus, hypertriglyceridemia, and hypertension. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the perilipin family.

RefSeq proteins (2): NP_001138783, NP_002657* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004279	Perilipin	Family
IPR042998	PLIN1	Family

Pfam: PF03036

UniProt features (27 total): modified residue 15, region of interest 4, sequence variant 4, compositionally biased region 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60240-F1	54.52	0.00

Functional residue map

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

Post-translational modifications (15): 130, 132, 137, 174, 299, 301, 382, 384, 408, 436, 497, 499, 81, 85, 126

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-163560	Triglyceride catabolism
R-HSA-381340	Transcriptional regulation of white adipocyte differentiation
R-HSA-9031528	NR1H2 & NR1H3 regulate gene expression linked to triglyceride lipolysis in adipose
R-HSA-9841922	MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis

MSigDB gene sets: 172 (showing top): REACTOME_TRIGLYCERIDE_CATABOLISM, REACTOME_TRANSCRIPTIONAL_REGULATION_OF_WHITE_ADIPOCYTE_DIFFERENTIATION, GOBP_RESPONSE_TO_COLD, GOBP_REGULATION_OF_TRIGLYCERIDE_METABOLIC_PROCESS, MODULE_255, GOBP_NEGATIVE_REGULATION_OF_LIPID_METABOLIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_REGULATION_OF_LIPID_METABOLIC_PROCESS, MODULE_379, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_REGULATION_OF_TRIGLYCERIDE_CATABOLIC_PROCESS, KEGG_PPAR_SIGNALING_PATHWAY, GOBP_NEUTRAL_LIPID_CATABOLIC_PROCESS, PPAR_DR1_Q2, GOBP_LIPID_METABOLIC_PROCESS

GO Biological Process (3): lipid metabolic process (GO:0006629), lipid catabolic process (GO:0016042), cellular response to cold (GO:0070417)

GO Molecular Function (2): lipid binding (GO:0008289), protein binding (GO:0005515)

GO Cellular Component (4): endoplasmic reticulum (GO:0005783), lipid droplet (GO:0005811), cytosol (GO:0005829), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Triglyceride metabolism	1
Adipogenesis	1
NR1H2 and NR1H3-mediated signaling	1
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
cytoplasm	2
cellular anatomical structure	2
primary metabolic process	1
lipid metabolic process	1
catabolic process	1
response to cold	1
cellular response to stress	1
endomembrane system	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

2942 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLIN1	LIPE	Q05469	996
PLIN1	ABHD5	Q8WTS1	995
PLIN1	PLIN4	Q96Q06	967
PLIN1	CIDEC	Q96AQ7	959
PLIN1	PNPLA2	Q96AD5	943
PLIN1	CIDEA	O60543	926
PLIN1	MFN2	O95140	892
PLIN1	PPARG	P37231	852
PLIN1	FABP4	P15090	774
PLIN1	ADIPOQ	Q15848	767
PLIN1	FASN	P49327	759
PLIN1	UCP1	P25874	756
PLIN1	SLC2A4	P14672	745
PLIN1	CD36	P16671	743
PLIN1	SCARB2	Q14108	733

IntAct

5 interactions, top by confidence:

A	B	Type	Score
AQP7	PLIN1	psi-mi:“MI:0914”(association)	0.570
PLIN1	AQP7	psi-mi:“MI:2364”(proximity)	0.570
PLIN1	AQP7	psi-mi:“MI:0915”(physical association)	0.570
PLIN1	AQP7	psi-mi:“MI:0403”(colocalization)	0.570

BioGRID (23): PLIN1 (FRET), PLIN1 (FRET), PLIN1 (PCA), PLIN1 (PCA), PLIN1 (PCA), PLIN1 (FRET), PLIN1 (FRET), PLIN1 (Affinity Capture-Western), SQSTM1 (Co-localization), PLIN1 (Co-localization), BSCL2 (Affinity Capture-Western), BSCL2 (PCA), SQSTM1 (Affinity Capture-Western), PLIN1 (Affinity Capture-Western), CCDC185 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A9P5BNK0, A2Y0H2, A6QLL0, B0FJL7, E9F970, F4JNX2, M0R7Z9, O48832, O60240, O60664, O82246, O82803, P0DKW0, P0DMN9, P0DMS3, P0DOC1, P0DP52, P0DTQ9, P0DUX6, P0DUX7, P0DUY0, P0DUY1, P12278, P15252, P18658, P19034, P29530, P43883, P43884, Q00368, Q00G26, Q41112, Q4PLW0, Q5BLZ2, Q5RAV8, Q69YL0, Q84K90, Q8BVZ1, Q8CGN5, Q99541

Diamond homologs: A6QLL0, B0FJL7, M0R7Z9, O60240, O60664, P43883, Q00G26, Q4PLW0, Q5BLZ2, Q5RAV8, Q8BVZ1, Q8CGN5, Q99541, Q9DBG5, Q9TUM6, Q96Q06, P43884, O88492, E9F970

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
PRKACA	“down-regulates activity”	PLIN1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	3
Uncertain significance	106
Likely benign	18
Benign	27

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
1342123	NM_002666.5(PLIN1):c.1308_1309del (p.Pro439fs)	Pathogenic
1342124	NM_002666.5(PLIN1):c.1201_1202dup (p.Val402fs)	Pathogenic
29827	NM_002666.5(PLIN1):c.1210-1G>T	Pathogenic
29828	NM_002666.5(PLIN1):c.1191_1192del (p.Val398fs)	Pathogenic
995943	NM_002666.5(PLIN1):c.1210-1del	Pathogenic
1175876	GRCh37/hg19 15q26.1(chr15:90220676-90220734)x1	Likely pathogenic
3065014	NM_002666.5(PLIN1):c.277C>T (p.Arg93Ter)	Likely pathogenic
3775979	NM_002666.5(PLIN1):c.203_218del (p.Leu68fs)	Likely pathogenic

SpliceAI

1249 predictions. Top by Δscore:

Variant	Effect	Δscore
15:89667181:CCTG:C	acceptor_loss	1.0000
15:89667601:CCTCA:C	donor_gain	1.0000
15:89667605:A:AC	donor_gain	1.0000
15:89667606:C:CC	donor_gain	1.0000
15:89667606:CTGAA:C	donor_gain	1.0000
15:89667610:A:C	donor_gain	1.0000
15:89667636:T:TA	donor_gain	1.0000
15:89669496:TTAC:T	donor_loss	1.0000
15:89669497:TAC:T	donor_loss	1.0000
15:89669498:A:AC	donor_gain	1.0000
15:89669498:A:C	donor_loss	1.0000
15:89669498:AC:A	donor_gain	1.0000
15:89669499:C:CA	donor_gain	1.0000
15:89669499:CC:C	donor_gain	1.0000
15:89669499:CCA:C	donor_gain	1.0000
15:89669499:CCAG:C	donor_gain	1.0000
15:89669499:CCAGG:C	donor_gain	1.0000
15:89669668:AGGGG:A	acceptor_gain	1.0000
15:89669669:GGGG:G	acceptor_gain	1.0000
15:89669670:GGG:G	acceptor_gain	1.0000
15:89669671:GG:G	acceptor_gain	1.0000
15:89669673:C:CC	acceptor_gain	1.0000
15:89669673:C:T	acceptor_loss	1.0000
15:89669674:T:C	acceptor_loss	1.0000
15:89669677:G:C	acceptor_gain	1.0000
15:89669683:A:AC	acceptor_gain	1.0000
15:89669683:A:C	acceptor_gain	1.0000
15:89669684:T:C	acceptor_gain	1.0000
15:89669684:T:TC	acceptor_gain	1.0000
15:89669685:T:C	acceptor_gain	1.0000

AlphaMissense

3350 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:89671531:A:G	L95S	0.996
15:89671555:G:T	A87D	0.996
15:89671522:A:G	L98P	0.995
15:89671543:G:T	A91D	0.995
15:89671501:A:T	L105H	0.994
15:89671510:A:G	I102T	0.994
15:89671552:T:A	N88I	0.992
15:89671556:C:G	A87P	0.992
15:89671546:A:G	L90P	0.990
15:89671537:C:G	R93P	0.989
15:89673325:C:A	K45N	0.989
15:89673325:C:G	K45N	0.989
15:89673380:A:G	L27P	0.987
15:89671522:A:T	L98Q	0.986
15:89671504:G:T	A104D	0.985
15:89671551:A:C	N88K	0.985
15:89671551:A:T	N88K	0.985
15:89671501:A:G	L105P	0.984
15:89671544:C:G	A91P	0.984
15:89673254:G:T	A69D	0.984
15:89670231:A:G	L116P	0.983
15:89671510:A:C	I102S	0.983
15:89673339:A:C	Y41D	0.983
15:89671518:C:A	E99D	0.982
15:89671518:C:G	E99D	0.982
15:89671534:C:T	G94D	0.981
15:89671535:C:G	G94R	0.981
15:89673221:A:G	L80P	0.981
15:89673230:A:T	V77D	0.981
15:89673392:C:G	R23P	0.981

dbSNP variants (sampled 300 via entrez): RS1000344415 (15:89673605 T>C,G), RS1000778456 (15:89674668 G>A), RS1000948440 (15:89666835 G>A,C), RS1001132824 (15:89673931 C>T), RS1001172221 (15:89665075 G>A), RS1001233687 (15:89666595 A>C), RS1001332725 (15:89679433 C>T), RS1001487805 (15:89664304 G>A), RS1001596512 (15:89675936 C>T), RS1001687126 (15:89665412 A>C,G,T), RS1001724375 (15:89670637 C>T), RS1001776644 (15:89670339 G>A,C), RS1001876062 (15:89680525 T>C,G), RS1001915011 (15:89664621 G>A), RS1002077659 (15:89675567 A>C)

Disease associations

OMIM: gene MIM:170290 | disease phenotypes: MIM:613877

GenCC curated gene-disease

Disease	Classification	Inheritance
PLIN1-related familial partial lipodystrophy	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
PLIN1-related familial partial lipodystrophy	Definitive	AD

Mondo (2): PLIN1-related familial partial lipodystrophy (MONDO:0013478), monogenic diabetes (MONDO:0015967)

Orphanet (2): PLIN1-related familial partial lipodystrophy (Orphanet:280356), Rare genetic diabetes mellitus (Orphanet:183625)

HPO phenotypes

24 total (24 of 24 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000147	Polycystic ovaries
HP:0000789	Infertility
HP:0000822	Hypertension
HP:0000831	Insulin-resistant diabetes mellitus
HP:0000842	Hyperinsulinemia
HP:0000855	Insulin resistance
HP:0000876	Oligomenorrhea
HP:0000877	Insulin-resistant diabetes mellitus at puberty
HP:0000956	Acanthosis nigricans
HP:0001297	Stroke
HP:0001395	Hepatic fibrosis
HP:0001397	Hepatic steatosis
HP:0002155	Hypertriglyceridemia
HP:0003117	Abnormal circulating hormone concentration
HP:0003635	Loss of subcutaneous adipose tissue in limbs
HP:0003712	Skeletal muscle hypertrophy
HP:0003758	Reduced subcutaneous adipose tissue
HP:0005268	Miscarriage
HP:0008981	Calf muscle hypertrophy
HP:0009017	Loss of gluteal subcutaneous adipose tissue
HP:0009125	Lipodystrophy
HP:0011462	Young adult onset
HP:0100578	Lipoatrophy

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002337_158	Amyotrophic lateral sclerosis (sporadic)	4.000000e-06
GCST006611_12	HDL cholesterol	3.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1741164 (SINGLE PROTEIN), CHEMBL3883313 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

7 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 269,366 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL193	NIFEDIPINE	4	74,353
CHEMBL388590	BENZBROMARONE	4	8,245
CHEMBL456	ETHACRYNIC ACID	4	20,004
CHEMBL590	MENADIONE	4	21,034
CHEMBL964	DISULFIRAM	4	38,611
CHEMBL140	CURCUMIN	3	93,882
CHEMBL51085	EBSELEN	3	13,237

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs894160	Toxicity	3	rosiglitazone	Diabetes Mellitus;Type 2;Weight gain

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs894160	PLIN1	3	3.00	1	rosiglitazone
rs2304795	PLIN1		0.00	0
rs1052700	KIF7, PLIN1		0.00	0
rs2289487	PLIN1		0.00	0

Binding affinities (BindingDB)

196 measured of 258 human assays (278 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
(4-acetyloxy-3-chloranyl-2-morpholin-4-yl-naphthalen-1-yl) ethanoate	EC50	0.133 nM
(5R)-6-[6-[(1E,3S,5Z)-3-hydroxyundeca-1,5-dienyl]pyridin-2-yl]hexane-1,5-diol	KI	25 nM
N-[4-(methoxymethyl)-1-(2-thiophen-2-ylethyl)piperidin-4-yl]-N-phenyl-propanamide;2-oxidanylpropane-1,2,3-tricarboxylic acid	KI	50 nM
SMR000469200	KI	126 nM
MLS000122969	IC50	127 nM
2-{2-ethoxy-5-[(4-ethylpiperazine-1-)sulfonyl]phenyl}-5-methyl-7-propyl-3H,4H-imidazo[1,5-a][1,2,4]triazin-4-one	IC50	300 nM
(3Z,5E)-1-ethyl-3,5-bis(3-hydroxy-4-methoxy-benzylidene)-4-piperidone	EC50	380 nM
2-butyl-4-thiazolidinecarboxylic acid	IC50	814 nM
N-cyclohexyl-2-[3-(2-furanyl)-2-oxo-1-quinoxalinyl]-2-phenylacetamide	IC50	817 nM
SMR001821229	IC50	828 nM
cid_53383152	IC50	970 nM
5-hydroxy-4-[[4-(2-hydroxyethyl)-1-piperazinyl]methyl]-2-methyl-3-benzo[g]benzofurancarboxylic acid ethyl ester	IC50	1130 nM
7-methyl-1,3-dinitro-acridine	EC50	1190 nM
MLS000684313	IC50	1230 nM
N-benzyl-2-(4-cyanophenyl)-2-[3-(furan-2-yl)-2-oxoquinoxalin-1-yl]acetamide	IC50	1300 nM
cid_53383173	IC50	1340 nM
cid_53383343	IC50	1400 nM
cid_53383347	IC50	1480 nM
N-cyclohexyl-2-[3-(2-furanyl)-2-oxo-1-quinoxalinyl]-2-(1-naphthalenyl)acetamide	IC50	1480 nM
cid_6377798	IC50	1560 nM
MLS000680483	IC50	1590 nM
(E)-2-cyano-3-[3-[(E)-2-cyano-3-(2-methoxyethylamino)-3-oxidanylidene-prop-1-enyl]phenyl]-N-(2-methoxyethyl)prop-2-enamide	EC50	1650 nM
N-tert-butyl-2-cyclopropyl-2-[3-(2-furanyl)-2-oxo-1-quinoxalinyl]acetamide	IC50	1720 nM
N-cyclohexyl-2-[3-(2-furanyl)-2-oxo-1-quinoxalinyl]-2-(4-methoxyphenyl)acetamide	IC50	1750 nM
N-tert-butyl-2-[3-(2-furanyl)-2-oxo-1-quinoxalinyl]-2-(4-methoxyphenyl)acetamide	IC50	1780 nM
MLS003674221	IC50	1810 nM
cid_53383334	IC50	1840 nM
N-tert-butyl-2-(2-fluorophenyl)-2-[3-(furan-2-yl)-2-oxoquinoxalin-1-yl]acetamide	IC50	1850 nM
MLS003674201	IC50	1860 nM
MLS003674212	IC50	1860 nM
N-Tosyl-L-phenylalanine chloromethyl ketone	IC50	1870 nM
MLS000779343	IC50	1870 nM
SMR000132574	IC50	1870 nM
1-(2-fluorophenyl)-5-{4-[(5-nitro-2-pyridinyl)oxy]benzylidene}-2,4,6(1H,3H,5H)-pyrimidinetrione	IC50	1880 nM
N-tert-butyl-2-[3-(furan-2-yl)-2-oxoquinoxalin-1-yl]-2-(4-phenylphenyl)acetamide	IC50	1910 nM
2-(1-benzofuran-2-yl)-2-[3-(furan-2-yl)-2-oxoquinoxalin-1-yl]-N-pentylacetamide	IC50	2000 nM
cid_53383163	IC50	2020 nM
methyl 1-(2-furylmethyl)-2-methyl-4-(4-nitrobenzylidene)-5-oxo-4,5-dihydro-1H-pyrrole-3-carboxylate	IC50	2070 nM
MLS000517420	IC50	2170 nM
cid_53383333	IC50	2170 nM
2-(1-benzofuran-2-yl)-N-cyclohexyl-2-[3-(furan-2-yl)-2-oxidanylidene-quinoxalin-1-yl]ethanamide	IC50	2190 nM
cid_2261569	IC50	2210 nM
N-cyclohexyl-2-[3-(furan-2-yl)-2-oxidanylidene-quinoxalin-1-yl]-2-quinolin-4-yl-ethanamide	IC50	2230 nM
2-(2-fluorophenyl)-2-[3-(furan-2-yl)-2-oxidanylidene-quinoxalin-1-yl]-N-(phenylmethyl)ethanamide	IC50	2240 nM
Cyclopentanone, 2-heptylidene-5-(1-pyrrolidinylmethyl)-, (E)-, hydrochloride	IC50	2250 nM
MLS000532188	IC50	2270 nM
N-tert-butyl-2-[3-(furan-2-yl)-2-oxoquinoxalin-1-yl]-2-naphthalen-1-ylacetamide	IC50	2270 nM
3-phenyl-1,4-benzodioxin-2-carboxaldehyde	EC50	2280 nM
MLS003674211	IC50	2400 nM
MLS003674210	IC50	2410 nM

ChEMBL bioactivities

32 potent at pChembl≥5 of 44 total, top 32 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.91	IC50	1227	nM	CHEMBL1565221
5.82	IC50	1520	nM	CHEMBL17201
5.73	IC50	1868	nM	TPCK
5.68	IC50	2068	nM	CHEMBL1500987
5.66	IC50	2207	nM	CHEMBL1535633
5.64	IC50	2278	nM	CHEMBL1369296
5.52	IC50	2992	nM	CHEMBL1414703
5.50	IC50	3170	nM	CHEMBL1598561
5.48	IC50	3339	nM	CHEMBL1462108
5.48	IC50	3291	nM	CHEMBL1363719
5.47	IC50	3410	nM	EBSELEN
5.41	IC50	3912	nM	CHEMBL1352555
5.38	IC50	4194	nM	CHALCONE
5.38	IC50	4190	nM	ETHACRYNIC ACID
5.36	IC50	4420	nM	CHEMBL1507428
5.36	IC50	4375	nM	CHEMBL1522846
5.35	IC50	4462	nM	CHEMBL1548890
5.32	IC50	4803	nM	CHEMBL1498750
5.30	IC50	5052	nM	CHEMBL1256923
5.25	IC50	5597	nM	CHEMBL485636
5.17	IC50	6718	nM	CHEMBL1366427
5.17	IC50	6794	nM	CHEMBL1517036
5.17	IC50	6842	nM	CHEMBL1308170
5.16	IC50	6855	nM	CHEMBL1519501
5.16	IC50	6959	nM	DISULFIRAM
5.15	IC50	7104	nM	CHEMBL1478754
5.13	IC50	7335	nM	CHEMBL1426508
5.10	IC50	7895	nM	MENADIONE
5.06	IC50	8781	nM	CHEMBL1334291
5.06	IC50	8678	nM	CHEMBL1433108
5.04	IC50	9167	nM	CURCUMIN
5.02	IC50	9619	nM	NIFEDIPINE

CTD chemical–gene interactions

48 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Dexamethasone	affects cotreatment, increases expression	5
sodium arsenite	decreases reaction, affects reaction, affects expression, decreases expression	4
Troglitazone	affects cotreatment, increases expression	3
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	3
triphenyl phosphate	affects cotreatment, increases expression	2
perfluorooctane sulfonic acid	increases expression, affects expression	2
bisphenol S	increases expression	2
Rosiglitazone	increases expression, affects response to substance	2
Benzo(a)pyrene	affects cotreatment, decreases expression, increases methylation	2
Valproic Acid	decreases expression	2
aristolochic acid I	increases expression	1
Firemaster 550	affects cotreatment, increases expression	1
bisphenol F	increases expression	1
sotorasib	affects cotreatment, decreases expression	1
propionaldehyde	decreases expression	1
benzo(b)fluoranthene	affects cotreatment, decreases expression	1
bisphenol A	affects expression	1
tributyltin	affects cotreatment, increases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	increases expression	1
benz(a)anthracene	affects cotreatment, decreases expression	1
chrysene	affects cotreatment, decreases expression	1
stearic acid	increases expression	1
beta-glycerophosphoric acid	affects cotreatment, increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
pentanal	decreases expression	1
BQ 610	decreases expression, decreases reaction	1
bisphenol B	increases expression	1
trametinib	decreases expression, affects cotreatment	1
NVP-BKM120	affects cotreatment, decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 1 functional, 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2114820	Functional	PubChem BioAssay. Counterscreen for inhibitors of the interaction of the lipase co-activator protein, abhydrolase domain containing 5 (ABHD5) with perilipin-5 (MLDP; PLIN5): Luminescence-based biochemical high throughput dose response assay	PubChem BioAssay data set
CHEMBL1738098	Binding	PUBCHEM_BIOASSAY: Luminescence-based biochemical high throughput dose response assay for inhibitors of the interaction of the lipase co-activator protein, abhydrolase domain containing 5 (ABHD5) with perilipin-1 (PLIN1) (2K validation set).	PubChem BioAssay data set

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06976658	PHASE2	RECRUITING	Glucokinase Activator in Monogenic Diabetes
NCT01795144	PHASE1	COMPLETED	Incretin Regulation of Insulin Secretion in Monogenic Diabetes
NCT04409795	PHASE2/PHASE3	COMPLETED	Oral Hypoglycemic Therapy for Monogenic Variant Carriers of the Joslin Medalist Study
NCT03988764	Not specified	RECRUITING	Monogenic Diabetes Misdiagnosed as Type 1
NCT05586594	Not specified	NOT_YET_RECRUITING	Identifying Maturity-onset Diabetes of the Young in Emirati Patients
NCT06478121	Not specified	RECRUITING	Understanding Beta Cell Disorders Through the Study of Rare Genotypes (ENDURE)
NCT06746610	Not specified	RECRUITING	Screening and Molecular Diagnosis-based Individualized Precision Management of Monogenic Diabetes
NCT07492004	Not specified	RECRUITING	China Monogenic Diabetes Registry
NCT07564518	Not specified	NOT_YET_RECRUITING	Application of FreeStyle Libre 2 for Evaluating Glycemic Variability Characteristics in Patients With Extreme Glucose Metabolism Phenotypes