PLIN1

Chr 15AD

perilipin 1

Also known as: FPLD4, PERI, PLIN

NCBI Gene: 5346 ENSG00000166819 UniProt: O60240 OMIM: 170290

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.

OMIM 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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Lipodystrophy, familial partial, type 4MIM #613877

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · PLIN1-related familial partial lipodystrophy · AD · ClinGen 2025

Active trials

103

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.26

LOEUF

Multiple*

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in PLIN1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 46

863 rare PASS variants

Rare truncating (LoF)

1 in 510

132 rare PASS variants

Rare synonymous (reference)

1 in 120

386 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PLIN1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 85	1 in 500
South Asian	~43k	1 in 47	1 in 920
Remaining (unassigned)	~30k	1 in 58	1 in 530
European (Finnish)	~27k	1 in 180	1 in 2,800
Admixed American	~22k	1 in 58	1 in 440
African / African American	~21k	1 in 54	1 in 470
East Asian	~20k	1 in 76	1 in 790
Ashkenazi Jewish	~13k	1 in 210	1 in 900
Middle Eastern	~2,884	1 in 54	1 in 410

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 7 of 8 coding exons well covered in gnomAD exomes; exon 9 marginal. Genomes: all 8.? see exons ↓