Lipodystrophy, familial partial, type 9

Summary

Lipodystrophy, familial partial, type 9 (MONDO:0958034) is a disease caused by PLAAT3 (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: PLAAT3 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 4

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		7	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	lipodystrophy, familial partial, type 9
Mondo ID	MONDO:0958034
OMIM	620683
Orphanet	686999
UMLS	C5882746
MedGen	1845936
GARD	0026915
Is cancer (heuristic)	no

Data availability: 4 ClinVar variants · 3 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 › lipodystrophy, familial partial, type 9

Related subtypes (9): familial partial lipodystrophy, Dunnigan type, PPARG-related familial partial lipodystrophy, familial partial lipodystrophy, Kobberling type, PLIN1-related familial partial lipodystrophy, 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

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

4 retrieved; paginated sample, class counts are floors:

3 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2691740	NM_001128203.2(PLAAT3):c.16-4823_118+167del	PLAAT3	Pathogenic	no assertion criteria provided
2691741	NM_001128203.2(PLAAT3):c.286dup (p.Ala96fs)	PLAAT3	Pathogenic	no assertion criteria provided
2691742	NM_001128203.2(PLAAT3):c.339C>A (p.Cys113Ter)	PLAAT3	Pathogenic	no assertion criteria provided
4845839	NM_001128203.2(PLAAT3):c.387+2T>C	PLAAT3	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
PLAAT3	Strong	Autosomal recessive	lipodystrophy, familial partial, type 9	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PLAAT3	Orphanet:686999	Lipodystrophy-demyelinating peripheral sensory-motor neuropathy syndrome

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
PLAAT3	HGNC:17825	ENSG00000176485	P53816	Phospholipase A and acyltransferase 3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PLAAT3	Phospholipase A and acyltransferase 3	Exhibits both phospholipase A1/2 and acyltransferase activities.

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)
PLAAT3	Other/Unknown	no		LRAT_dom, H-rev107_PLA/AT

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
C1 segment of cervical spinal cord	1
corpus callosum	1
spinal cord	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PLAAT3	287	ubiquitous	marker	C1 segment of cervical spinal cord, spinal cord, corpus callosum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PLAAT3	2,953

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PLAAT3	P53816	7

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
Acyl chain remodelling of PI	1	671.8×	0.003	PLAAT3
Acyl chain remodelling of PS	1	519.1×	0.003	PLAAT3
Acyl chain remodelling of PC	1	423.0×	0.003	PLAAT3
Acyl chain remodelling of PE	1	393.8×	0.003	PLAAT3

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
membrane disassembly	1	16852.0×	4e-04	PLAAT3
regulation of adipose tissue development	1	16852.0×	4e-04	PLAAT3
organelle disassembly	1	4213.0×	0.001	PLAAT3
ether lipid metabolic process	1	2808.7×	0.001	PLAAT3
N-acylphosphatidylethanolamine metabolic process	1	1872.4×	0.001	PLAAT3
phosphatidylethanolamine acyl-chain remodeling	1	1404.3×	0.002	PLAAT3
lens fiber cell differentiation	1	1053.2×	0.002	PLAAT3
peroxisome organization	1	802.5×	0.002	PLAAT3
phospholipid biosynthetic process	1	674.1×	0.002	PLAAT3
triglyceride metabolic process	1	443.5×	0.003	PLAAT3
phospholipid metabolic process	1	343.9×	0.003	PLAAT3
lipid catabolic process	1	244.2×	0.004	PLAAT3
response to bacterium	1	193.7×	0.005	PLAAT3

Therapeutics

Drug target analysis

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

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

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PLAAT3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
PLAAT3	2	Binding:2

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

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
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	1	PLAAT3

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PLAAT3	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.