PLIN1-related familial partial lipodystrophy

Summary

PLIN1-related familial partial lipodystrophy (MONDO:0013478) is a disease caused by PLIN1 (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: PLIN1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 23
• Phenotypes (HPO): 16

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		3	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

16 HPO clinical features (Orphanet curated; top 16 by frequency):

HPO ID	Term	Frequency
HP:0000822	Hypertension	Obligate (100%)
HP:0000842	Hyperinsulinemia	Obligate (100%)
HP:0000877	Insulin-resistant diabetes mellitus at puberty	Obligate (100%)
HP:0000956	Acanthosis nigricans	Obligate (100%)
HP:0001397	Hepatic steatosis	Obligate (100%)
HP:0002155	Hypertriglyceridemia	Obligate (100%)
HP:0100578	Lipoatrophy	Obligate (100%)
HP:0000789	Infertility	Very frequent (80-99%)
HP:0003635	Loss of subcutaneous adipose tissue in limbs	Very frequent (80-99%)
HP:0003758	Reduced subcutaneous adipose tissue	Very frequent (80-99%)
HP:0008981	Calf muscle hypertrophy	Very frequent (80-99%)
HP:0009017	Loss of gluteal subcutaneous adipose tissue	Very frequent (80-99%)
HP:0000147	Polycystic ovaries	Frequent (30-79%)
HP:0000876	Oligomenorrhea	Frequent (30-79%)
HP:0001395	Hepatic fibrosis	Frequent (30-79%)
HP:0003117	Abnormality of circulating hormone level	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	PLIN1-related familial partial lipodystrophy
Mondo ID	MONDO:0013478
OMIM	613877
Orphanet	280356
DOID	DOID:0070205
UMLS	C5191005
MedGen	1675945
GARD	0012601
Is cancer (heuristic)	no

Also known as: familial partial lipodystrophy associated with PLIN1 mutations · familial partial lipodystrophy type 4 · FPLD due to PLIN1 mutations · FPLD4 · lipodystrophy, familial partial, type 4 · PLIN1-related FPLD

Data availability: 23 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › lipodystrophy › hereditary lipodystrophy › familial partial lipodystrophy › PLIN1-related familial partial lipodystrophy

Related subtypes (9): familial partial lipodystrophy, Dunnigan type, PPARG-related familial partial lipodystrophy, familial partial lipodystrophy, Kobberling type, CIDEC-related familial partial lipodystrophy, LIPE-related familial partial lipodystrophy, autosomal semi-dominant severe lipodystrophic laminopathy, AKT2-related familial partial lipodystrophy, lipodystrophy, familial partial, type 8, lipodystrophy, familial partial, type 9

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

23 retrieved; paginated sample, class counts are floors:

10 uncertain significance, 5 pathogenic, 4 benign, 2 likely pathogenic, 2 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1342123	NM_002666.5(PLIN1):c.1308_1309del (p.Pro439fs)	PLIN1	Pathogenic	no assertion criteria provided
1342124	NM_002666.5(PLIN1):c.1201_1202dup (p.Val402fs)	PLIN1	Pathogenic	no assertion criteria provided
29827	NM_002666.5(PLIN1):c.1210-1G>T	PLIN1	Pathogenic	no assertion criteria provided
29828	NM_002666.5(PLIN1):c.1191_1192del (p.Val398fs)	PLIN1	Pathogenic	no assertion criteria provided
995943	NM_002666.5(PLIN1):c.1210-1del	PLIN1	Pathogenic	criteria provided, single submitter
3065014	NM_002666.5(PLIN1):c.277C>T (p.Arg93Ter)	PLIN1	Likely pathogenic	criteria provided, single submitter
3775979	NM_002666.5(PLIN1):c.203_218del (p.Leu68fs)	PLIN1	Likely pathogenic	criteria provided, single submitter
3388231	NM_002666.5(PLIN1):c.1284_1286dup (p.Arg429_Glu430insArg)	PLIN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
634585	NM_002666.5(PLIN1):c.902C>T (p.Thr301Met)	PLIN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
976014	NM_002666.5(PLIN1):c.224C>T (p.Pro75Leu)	LOC125146351	Uncertain significance	criteria provided, multiple submitters, no conflicts
1029621	NM_002666.5(PLIN1):c.1033A>G (p.Thr345Ala)	PLIN1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1033942	NM_002666.5(PLIN1):c.269T>C (p.Leu90Pro)	PLIN1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1339162	NM_002666.5(PLIN1):c.691C>T (p.Arg231Ter)	PLIN1	Uncertain significance	criteria provided, single submitter
2435085	NM_002666.5(PLIN1):c.1280A>G (p.Glu427Gly)	PLIN1	Uncertain significance	criteria provided, single submitter
3600402	NM_002666.5(PLIN1):c.1559A>G (p.Lys520Arg)	PLIN1	Uncertain significance	criteria provided, single submitter
3780444	NM_002666.5(PLIN1):c.964-1G>C	PLIN1	Uncertain significance	criteria provided, single submitter
3892119	NM_002666.5(PLIN1):c.1503C>A (p.Phe501Leu)	PLIN1	Uncertain significance	criteria provided, single submitter
3892120	NM_002666.5(PLIN1):c.358A>G (p.Ile120Val)	PLIN1	Uncertain significance	criteria provided, single submitter
4526474	NM_002666.5(PLIN1):c.502C>T (p.Arg168Ter)	PLIN1	Uncertain significance	criteria provided, single submitter
1250333	NM_002666.5(PLIN1):c.772-23T>A	PLIN1	Benign	criteria provided, multiple submitters, no conflicts
129970	NM_002666.5(PLIN1):c.1113T>C (p.Pro371=)	PLIN1	Benign	criteria provided, multiple submitters, no conflicts
129971	NM_002666.5(PLIN1):c.1119C>T (p.Val373=)	PLIN1	Benign	criteria provided, multiple submitters, no conflicts
129973	NM_002666.5(PLIN1):c.580C>G (p.Pro194Ala)	PLIN1	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
PLIN1	Strong	Autosomal dominant	PLIN1-related familial partial lipodystrophy	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PLIN1	Orphanet:280356	PLIN1-related familial partial lipodystrophy

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PLIN1	HGNC:9076	ENSG00000166819	O60240	Perilipin-1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PLIN1	Perilipin-1	Modulator of adipocyte lipid metabolism.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PLIN1	Other/Unknown	no		Perilipin, PLIN1

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adipose tissue	1
adipose tissue of abdominal region	1
subcutaneous adipose tissue	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PLIN1	194	broad	marker	subcutaneous adipose tissue, adipose tissue, adipose tissue of abdominal region

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PLIN1	2,970

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PLIN1	O60240	54.52

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
NR1H2 & NR1H3 regulate gene expression linked to triglyceride lipolysis in adipose	1	2284.0×	0.002	PLIN1
Triglyceride catabolism	1	475.8×	0.004	PLIN1
Transcriptional regulation of white adipocyte differentiation	1	129.8×	0.010	PLIN1
MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis	1	82.8×	0.012	PLIN1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cellular response to cold	1	1053.2×	0.003	PLIN1
lipid catabolic process	1	244.2×	0.006	PLIN1
lipid metabolic process	1	91.6×	0.011	PLIN1

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
PLIN1	NIFEDIPINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PLIN1	7	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
NIFEDIPINE	4	PLIN1
BENZBROMARONE	4	PLIN1
ETHACRYNIC ACID	4	PLIN1
MENADIONE	4	PLIN1
DISULFIRAM	4	PLIN1
CURCUMIN	3	PLIN1
EBSELEN	3	PLIN1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
PLIN1	2	Functional:1, Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

7 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
NIFEDIPINE	4	PLIN1
BENZBROMARONE	4	PLIN1
ETHACRYNIC ACID	4	PLIN1
MENADIONE	4	PLIN1
DISULFIRAM	4	PLIN1
CURCUMIN	3	PLIN1
EBSELEN	3	PLIN1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PLIN1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.