PLIN1

Chr 15

perilipin 1

Also known as: FPLD4, PERI, PLIN

NCBI Gene: 5346 ENSG00000166819 UniProt: O60240

The protein coats lipid storage droplets in adipocytes to protect them from breakdown by hormone-sensitive lipase and modulates adipocyte lipid metabolism. Mutations cause familial partial lipodystrophy type 4, characterized by abnormal fat distribution and metabolic dysfunction. Inheritance is autosomal dominant.

ResearchSummary from RefSeq, OMIM, UniProt

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. [provided by RefSeq, Feb 2009]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.26

Clinical Summary— PLIN1

🧬

Gene-Disease Validity (ClinGen)

PLIN1-related familial partial lipodystrophy · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

7 unique Pathogenic / Likely Pathogenic· 124 VUS of 195 total submissions

💊

Clinical Trials

3 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.26LOEUF

pLI 0.000

Z-score 0.64

OE 0.85 (0.59–1.26)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.93Z-score

OE missense 1.16 (1.06–1.27)

317 obs / 273.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.85 (0.59–1.26)

0≤0.351.4

Missense OE?1.16 (1.06–1.27)

0≤0.61.4

Synonymous OE?1.14

0≤1.21.6

LoF obs/exp: 18 / 21.2Missense obs/exp: 317 / 273.7Syn Z: -1.17

This gene — mechanism propensity

0.6355th %ile

GOF

0.6150th %ile

LOF

0.3941th %ile

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). The Badonyi & Marsh model scores dominant-negative highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOF1 literature citation · 100% of P/LP variants are LoF

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Literature Evidence

LOFOur study suggests that heterozygous variants that are predicted to result in PLIN1 haploinsufficiency are not a cause of familial partial lipodystrophy and should not be reported as disease-causing variants by diagnostic genetic testing laboratories.1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

References

1.PMID 30020498 ↗

ClinVar Variant Classifications

195 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5

Likely Pathogenic2

VUS124

Likely Benign28

Benign27

Conflicting4

Pathogenic

Likely Pathogenic

124

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	5	0	0	0	5
Likely Pathogenic	2	0	0	0	2
VUS	10	112	1	1	124
Likely Benign	1	11	1	15	28
Benign	0	5	17	5	27
Conflicting	—				4
Total	18	128	19	21	190

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

38 pathogenic / likely-pathogenic (of 47) ClinVar copy-number / structural variants overlap PLIN1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →