PLIN4

Summary

PLIN4 (perilipin 4, HGNC:29393) is a protein-coding gene on chromosome 19p13.3, encoding Perilipin-4 (Q96Q06). May play a role in triacylglycerol packaging into adipocytes.

Members of the perilipin family, such as PLIN4, coat intracellular lipid storage droplets (Wolins et al., 2003 [PubMed 12840023]).

Source: NCBI Gene 729359 — RefSeq curated summary.

At a glance

• Gene–disease (curated): vacuolar Neuromyopathy (Moderate, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 485 total — 1 likely-pathogenic
• Phenotypes (HPO): 16
• MANE Select transcript: NM_001367868

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29393
Approved symbol	PLIN4
Name	perilipin 4
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	S3-12
Ensembl gene	ENSG00000167676
Ensembl biotype	protein_coding
OMIM	613247
Entrez	729359

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 11 protein_coding

ENST00000301286, ENST00000633942, ENST00000901550, ENST00000901551, ENST00000966619, ENST00000966620, ENST00000966621, ENST00000966622, ENST00000966623, ENST00000966624, ENST00000966625

RefSeq mRNA: 5 — MANE Select: NM_001367868 NM_001367868, NM_001393888, NM_001393889, NM_001393890, NM_001393891

CCDS: CCDS92489, CCDS92490

Canonical transcript exons

ENST00000301286 — 8 exons

Exon	Start	End
ENSE00001115516	4508768	4508955
ENSE00001115517	4504861	4504947
ENSE00001115518	4502192	4504785
ENSE00001554408	4516617	4516678
ENSE00003775570	4518222	4518289
ENSE00003776221	4517554	4517698
ENSE00003936019	4510446	4513701
ENSE00003938693	4518385	4518486

Expression profiles

Bgee: expression breadth ubiquitous, 220 present calls, max score 98.97.

FANTOM5 (CAGE): breadth broad, TPM avg 13.4481 / max 2098.7394, expressed in 221 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
178445	12.8922	203
178446	0.2880	110
178444	0.1935	78
178441	0.0527	28
178443	0.0217	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
subcutaneous adipose tissue	UBERON:0002190	98.97	gold quality
adipose tissue	UBERON:0001013	98.67	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.38	gold quality
apex of heart	UBERON:0002098	98.31	gold quality
gastrocnemius	UBERON:0001388	97.94	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.54	gold quality
adipose tissue of abdominal region	UBERON:0007808	97.54	gold quality
omental fat pad	UBERON:0010414	97.41	gold quality
peritoneum	UBERON:0002358	97.35	gold quality
left ventricle myocardium	UBERON:0006566	97.18	gold quality
pericardium	UBERON:0002407	96.97	gold quality
muscle of leg	UBERON:0001383	96.58	gold quality
skeletal muscle organ	UBERON:0014892	96.06	gold quality
heart left ventricle	UBERON:0002084	96.05	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	95.85	gold quality
cardiac ventricle	UBERON:0002082	95.84	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	95.53	gold quality
skeletal muscle tissue	UBERON:0001134	95.29	gold quality
body of tongue	UBERON:0011876	94.82	gold quality
right lobe of liver	UBERON:0001114	94.78	gold quality
cardiac atrium	UBERON:0002081	94.71	gold quality
right atrium auricular region	UBERON:0006631	94.58	gold quality
vena cava	UBERON:0004087	94.31	gold quality
muscle tissue	UBERON:0002385	94.16	gold quality
synovial joint	UBERON:0002217	94.13	gold quality
quadriceps femoris	UBERON:0001377	93.74	gold quality
myocardium	UBERON:0002349	93.64	gold quality
mammary duct	UBERON:0001765	93.51	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.49	gold quality
epithelium of mammary gland	UBERON:0003244	93.45	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.19

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 12)

• Characterization of homologous mouse gene product, plasma membrane associated protein, S3-12. (PMID:12840023)
• Those findings indicate improvement and conservation of lifestyle depending on genetic predisposition in ADIPOQ, PLIN and LIPE should be encouraged. (PMID:20495294)
• These results suggest variation at the PLIN4 locus, and its interaction with PUFA as a modulator of obesity related phenotypes, acts in part through creation of a miR-522 regulatory site (PMID:21533135)
• we found a significant association between one single-nucleotide polymorphism in PLIN4 and height but not with bone traits (PMID:22210160)
• PLIN2-PLIN5 proteins were all more abundant in women than in men (p = 0.037 and p < 0.0001, respectively), consistent with higher intramyocellular lipid content observed in female skeletal muscle. (PMID:22667335)
• Studied weight loss in obese patients with Perilipin 4 (PLIN4), Fat mass and obesity-associated (FTO), and beta- adrenergic receptor 3 (ADRB3) polymorphisms treated with Garcinia cambogia/Glucomannan. Results suggest weight loss was attenuated in carriers of PLIN4, FTO, ADRB3 polymorphisms. (PMID:29361938)
• Using synthetic lipids, we show that Plin4 amphipathic helix (AH) binds poorly to lipid bilayers but strongly interacts with pure triglycerides, acting as a coat and forming small oil droplets. Because Plin4 overexpression alleviates lipid droplet (LD) instability under conditions where their coverage by phospholipids is limiting, we propose that the Plin4 AH replaces the LD lipid monolayer, for example during LD growth. (PMID:29626194)
• We investigated whether the presence of the A allele of rs8887 SNP (PLIN4 gene), known to be associated with increased sensitivity to the consumption of n-3 PUFAs, interacts with fetal growth influencing inhibitory control. There was a significant interaction between birth weight and the presence of the A allele on SSRT performance,in which lower birth weight associated with poorer inhibitory control only in non-carrier (PMID:30293593)
• These findings underlie the importance of a novel morphologic-metabolic phenotype associated with chemotherapy resistance in triple-negative breast cancer , and bring to light novel therapeutic targets resulting from vulnerabilities in this phenotype, including the expression of PLIN4 essential for stabilizing lipid droplets in resistant cells. (PMID:31537618)
• Multiomic elucidation of a coding 99-mer repeat-expansion skeletal muscle disease. (PMID:32451610)
• Exceptional stability of a perilipin on lipid droplets depends on its polar residues, suggesting multimeric assembly. (PMID:33856341)
• PLIN4-related myopathy: clinical, histological and imaging data in a large cohort of patients. (PMID:37145156)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	plin3	ENSDARG00000013711
mus_musculus	Plin4	ENSMUSG00000002831
rattus_norvegicus	Plin4	ENSRNOG00000047046
drosophila_melanogaster	Lsd-2	FBGN0030608

Paralogs (4): PLIN3 (ENSG00000105355), PLIN2 (ENSG00000147872), PLIN1 (ENSG00000166819), PLIN5 (ENSG00000214456)

Protein

Protein identifiers

Perilipin-4 — Q96Q06 (reviewed: Q96Q06)

Alternative names: Adipocyte protein S3-12

All UniProt accessions (2): A0A0J9YXN7, Q96Q06

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in triacylglycerol packaging into adipocytes. May function as a coat protein involved in the biogenesis of lipid droplets.

Subcellular location. Cell membrane. Cytoplasm. Lipid droplet.

Disease relevance. Myopathy with rimmed ubiquitin-positive autophagic vacuolation, autosomal dominant (MRUPAV) [MIM:601846] An autosomal dominant, slowly progressive myopathy characterized by skeletal muscle weakness variably affecting the distal or proximal lower limbs. Some patients may also have upper limb involvement or neck muscle weakness. Skeletal muscle biopsy shows distinctive myopathic features including rimmed ubiquitin-positive autophagic vacuolation and abnormal subsarcolemmal protein aggregation. The disease is caused by variants affecting the gene represented in this entry. Disease causing variants are heterozygous expansions of a 99-bp repetitive sequence in exon 3. Normal repeat number is 29 to 31, whereas pathogenic repeats range from 39 to 50. A higher number of repeats may be associated with earlier age at disease onset, more severe phenotypes, and faster disease progression.

Induction. Up-regulated during adipocyte differentiation.

Similarity. Belongs to the perilipin family.

RefSeq proteins (5): NP_001354797, NP_001380817, NP_001380818, NP_001380819, NP_001380820 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004279	Perilipin	Family

Pfam: PF03036

UniProt features (58 total): repeat 27, sequence variant 11, sequence conflict 9, region of interest 5, compositionally biased region 3, modified residue 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96Q06-F1	35.66	0.02

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 (2): 25, 31

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9841922	MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis

MSigDB gene sets: 83 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, PEREZ_TP63_TARGETS, MARTINEZ_RB1_TARGETS_UP, PEREZ_TP53_AND_TP63_TARGETS, RUAN_RESPONSE_TO_TROGLITAZONE_UP, RUAN_RESPONSE_TO_TNF_DN, MARTINEZ_RB1_AND_TP53_TARGETS_UP, BURTON_ADIPOGENESIS_6, chr19p13, RAY_TUMORIGENESIS_BY_ERBB2_CDC25A_DN, CHEN_METABOLIC_SYNDROM_NETWORK, WANG_CLASSIC_ADIPOGENIC_TARGETS_OF_PPARG, BRUINS_UVC_RESPONSE_LATE, WAKABAYASHI_ADIPOGENESIS_PPARG_BOUND_8D, RATTENBACHER_BOUND_BY_CELF1

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (5): lipid droplet (GO:0005811), cytosol (GO:0005829), plasma membrane (GO:0005886), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
intracellular membraneless organelle	1
cytoplasm	1
membrane	1
cell periphery	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1713 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLIN4	PLIN1	O60240	967
PLIN4	CIDEC	Q96AQ7	660
PLIN4	PLIN2	Q99541	659
PLIN4	ABHD5	Q8WTS1	627
PLIN4	LIPE	Q05469	626
PLIN4	CIDEA	O60543	611
PLIN4	RAB18	Q9NP72	610
PLIN4	PNPLA2	Q96AD5	594
PLIN4	ADIPOQ	Q15848	594
PLIN4	INS	P01308	563
PLIN4	FITM2	Q8N6M3	514
PLIN4	PLIN3	O60664	485
PLIN4	TRARG1	Q8IXB3	455
PLIN4	GPAT4	Q86UL3	451
PLIN4	PPARG	P37231	448

IntAct

6 interactions, top by confidence:

A	B	Type	Score
PLIN4	CASP8	psi-mi:“MI:0915”(physical association)	0.370
Prkar2a	TBC1D31	psi-mi:“MI:0914”(association)	0.350
PPP1CA	ACO2	psi-mi:“MI:0914”(association)	0.350
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350
CEBPD	PTGES	psi-mi:“MI:0914”(association)	0.350

BioGRID (7): SMC3 (Co-fractionation), PLIN4 (Affinity Capture-MS), PLIN4 (Affinity Capture-MS), PLIN4 (Cross-Linking-MS (XL-MS)), ALDOA (Cross-Linking-MS (XL-MS)), PLIN4 (Affinity Capture-MS), PLIN4 (Two-hybrid)

ESM2 similar proteins: A0A0D1CKI0, A0A0H3K686, A0A6B9KZ90, A6QQF6, D2K835, O24006, O88492, P01357, P02674, P02894, P02976, P04922, P05222, P05226, P05995, P08672, P08673, P08674, P08675, P08676, P08677, P08798, P0A015, P0DRJ4, P13673, P13826, P14606, P38507, P81592, P99134, Q03110, Q03646, Q09180, Q1ELU4, Q1ELU5, Q28201, Q28298, Q29428, Q42626, Q42627

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	336
Likely benign	117
Benign	6

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
4687998	NM_001367868.2(PLIN4):c.258+2T>C	Likely pathogenic

SpliceAI

852 predictions. Top by Δscore:

Variant	Effect	Δscore
19:4504862:T:TA	donor_gain	1.0000
19:4504945:AATC:A	acceptor_loss	1.0000
19:4504948:C:CC	acceptor_gain	1.0000
19:4504948:C:T	acceptor_loss	1.0000
19:4508766:ACCAG:A	donor_gain	1.0000
19:4508767:CCAG:C	donor_gain	1.0000
19:4508767:CCAGC:C	donor_gain	1.0000
19:4516611:TCTCA:T	donor_loss	1.0000
19:4516612:CTCAC:C	donor_loss	1.0000
19:4516613:TCACC:T	donor_loss	1.0000
19:4516614:CAC:C	donor_loss	1.0000
19:4516615:A:AT	donor_loss	1.0000
19:4516616:C:A	donor_loss	1.0000
19:4516676:CCA:C	acceptor_gain	1.0000
19:4516677:CA:C	acceptor_gain	1.0000
19:4516677:CAC:C	acceptor_gain	1.0000
19:4516679:C:CC	acceptor_gain	1.0000
19:4516699:C:CT	acceptor_gain	1.0000
19:4517549:CTCA:C	donor_loss	1.0000
19:4517550:TCA:T	donor_loss	1.0000
19:4517551:CA:C	donor_loss	1.0000
19:4517552:A:AC	donor_gain	1.0000
19:4517552:AC:A	donor_gain	1.0000
19:4517552:ACC:A	donor_gain	1.0000
19:4517553:C:CC	donor_gain	1.0000
19:4517553:C:CT	donor_loss	1.0000
19:4517553:CC:C	donor_gain	1.0000
19:4517553:CCC:C	donor_gain	1.0000
19:4504783:CTCCT:C	acceptor_loss	0.9900
19:4504786:CTGT:C	acceptor_loss	0.9900

AlphaMissense

8804 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:4504500:A:G	W1345R	0.980
19:4504500:A:T	W1345R	0.980
19:4508787:A:G	L1214P	0.978
19:4504483:G:C	F1350L	0.977
19:4504483:G:T	F1350L	0.977
19:4504485:A:G	F1350L	0.977
19:4504736:A:G	L1266P	0.977
19:4508813:G:C	F1205L	0.970
19:4508813:G:T	F1205L	0.970
19:4508815:A:G	F1205L	0.970
19:4508809:C:G	A1207P	0.960
19:4504491:C:G	G1348R	0.958
19:4504491:C:T	G1348R	0.958
19:4504491:C:A	G1348W	0.955
19:4504498:C:A	W1345C	0.955
19:4504498:C:G	W1345C	0.955
19:4504490:C:T	G1348E	0.953
19:4504484:A:G	F1350S	0.947
19:4508892:A:T	V1179D	0.945
19:4508894:G:C	F1178L	0.944
19:4508894:G:T	F1178L	0.944
19:4508896:A:G	F1178L	0.944
19:4508829:A:G	L1200P	0.943
19:4510471:G:C	F1149L	0.942
19:4510471:G:T	F1149L	0.942
19:4510473:A:G	F1149L	0.942
19:4504484:A:C	F1350C	0.938
19:4504725:A:C	Y1270D	0.934
19:4508787:A:T	L1214H	0.932
19:4508842:C:G	A1196P	0.931

dbSNP variants (sampled 300 via entrez): RS1000003012 (19:4507390 A>C), RS1000165921 (19:4509602 C>T), RS1000349607 (19:4505968 C>G), RS1000361826 (19:4502295 G>A), RS1000397527 (19:4518601 C>A,T), RS1000592362 (19:4506517 A>G), RS1000746670 (19:4514463 C>T), RS1000910092 (19:4510282 C>T), RS1001089651 (19:4506720 C>T), RS1001388781 (19:4505155 C>T), RS1001547646 (19:4503568 C>T), RS1001911007 (19:4504291 TAAG>T), RS1002409787 (19:4520126 G>A), RS1002440685 (19:4508625 C>T), RS1002697031 (19:4518723 T>C)

Disease associations

OMIM: gene MIM:613247 | disease phenotypes: MIM:601846, MIM:135900, MIM:609943, MIM:614562

GenCC curated gene-disease

Disease	Classification	Inheritance
vacuolar Neuromyopathy	Moderate	Autosomal dominant

Mondo (2): vacuolar Neuromyopathy (MONDO:0011155), Coffin-Siris syndrome 1 (MONDO:0007617)

Orphanet (2): PLIN4-related distal myopathy (Orphanet:696063), Coffin-Siris syndrome (Orphanet:1465)

HPO phenotypes

16 total (16 of 16 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001618	Dysphonia
HP:0001761	Pes cavus
HP:0002015	Dysphagia
HP:0002460	Distal muscle weakness
HP:0003236	Elevated circulating creatine kinase concentration
HP:0003547	Shoulder girdle muscle weakness
HP:0003555	Muscle fiber splitting
HP:0003560	Muscular dystrophy
HP:0003581	Adult onset
HP:0003687	Centrally nucleated skeletal muscle fibers
HP:0003691	Scapular winging
HP:0003722	Neck flexor weakness
HP:0003805	Rimmed vacuoles
HP:0003828	Variable expressivity
HP:0009027	Foot dorsiflexor weakness

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST004601_185	Red blood cell count	8.000000e-14
GCST010083_97	Hemoglobin levels	9.000000e-38
GCST90000025_669	Appendicular lean mass	8.000000e-12
GCST90002396_12	Mean reticulocyte volume	2.000000e-19

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004305	erythrocyte count
EFO:0004509	hemoglobin measurement
EFO:0004980	appendicular lean mass
EFO:0010701	mean reticulocyte volume

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C566617	Vacuolar Neuromyopathy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, affects cotreatment, increases expression	3
perfluorooctane sulfonic acid	increases expression	2
bisphenol S	increases expression	2
Rosiglitazone	increases expression, increases reaction	2
Troglitazone	increases expression, increases reaction	2
Estradiol	decreases expression, increases expression, affects cotreatment	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
sotorasib	decreases expression, affects cotreatment	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
benzo(b)fluoranthene	affects cotreatment, increases expression	1
bisphenol A	decreases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
sodium arsenite	increases expression	1
perfluorooctanoic acid	increases expression	1
aflatoxin B2	increases methylation	1
benz(a)anthracene	affects cotreatment, increases expression	1
chrysene	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-nonanoic acid	increases expression	1
corosolic acid	decreases expression	1
nutlin 3	affects cotreatment, increases expression	1
bisphenol B	increases expression	1
muraglitazar	increases expression, increases reaction	1
tesaglitazar	increases expression, increases reaction	1
jinfukang	increases expression, affects cotreatment	1

Clinical trials (associated diseases)

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