Acquired partial lipodystrophy

Summary

Acquired partial lipodystrophy (MONDO:0012104) is a disease with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 4
• Phenotypes (HPO): 17

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 1 000 000		Europe	Validated

Signs & symptoms

Clinical features (HPO)

17 HPO clinical features (Orphanet curated; top 17 by frequency):

HPO ID	Term	Frequency
HP:0100578	Lipoatrophy	Very frequent (80-99%)
HP:0000365	Hearing impairment	Frequent (30-79%)
HP:0001249	Intellectual disability	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0002960	Autoimmunity	Frequent (30-79%)
HP:0003198	Myopathy	Frequent (30-79%)
HP:0005328	Progeroid facial appearance	Frequent (30-79%)
HP:0005421	Decreased circulating complement C3 concentration	Frequent (30-79%)
HP:0100827	Lymphocytosis	Frequent (30-79%)
HP:0000093	Proteinuria	Occasional (5-29%)
HP:0000855	Insulin resistance	Occasional (5-29%)
HP:0001397	Hepatic steatosis	Occasional (5-29%)
HP:0002230	Generalized hirsutism	Occasional (5-29%)
HP:0002721	Immunodeficiency	Occasional (5-29%)
HP:0002829	Arthralgia	Occasional (5-29%)
HP:0002907	Microscopic hematuria	Occasional (5-29%)
HP:0100820	Glomerulopathy	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	acquired partial lipodystrophy
Mondo ID	MONDO:0012104
MeSH	C562448
Orphanet	79087
ICD-11	2042663302
NCIT	C129723
SNOMED CT	75659004
UMLS	C0220989
MedGen	66352
GARD	0010509
Is cancer (heuristic)	no

Also known as: acquired partial lipodystrophy · APLD · Barraquer-Simons syndrome · lipodystophy partial progressive · lipodystrophy cephalothoracic type · lipodystrophy partial acquired · lipodystrophy, partial, acquired, susceptibility to · partial acquired lipodystrophy · progressive cephalothoracic lipodystrophy

Data availability: 4 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › acquired metabolic disease › acquired lipodystrophy › acquired partial lipodystrophy

Related subtypes (1): acquired generalized lipodystrophy

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:

1 benign/likely benign, 1 benign, 1 risk factor, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
208979	LMNB2, TYR232HIS	LMNB2	risk factor	no assertion criteria provided
14474	NM_032737.4(LMNB2):c.704G>A (p.Arg235Gln)	LMNB2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
14475	NM_032737.4(LMNB2):c.1279G>A (p.Ala427Thr)	LMNB2	Benign	criteria provided, single submitter
66746	NM_032737.4(LMNB2):c.265-6C>T	LMNB2	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LMNB2	Orphanet:457265	Progressive myoclonic epilepsy type 9
LMNB2	Orphanet:79087	Acquired 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
LMNB2	HGNC:6638	ENSG00000176619	Q03252	Lamin-B2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LMNB2	Lamin-B2	Lamins are intermediate filament proteins that assemble into a filamentous meshwork, and which constitute the major components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane.

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)
LMNB2	Other/Unknown	no		Lamin_tail_dom, IF_conserved, Lamin_tail_dom_sf

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
left testis	1
right testis	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LMNB2	194	ubiquitous	marker	ventricular zone, left testis, right testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LMNB2	3,562

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
LMNB2	Q03252	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
nuclear pore localization	1	3370.4×	0.001	LMNB2
protein localization to nuclear envelope	1	2106.5×	0.001	LMNB2
nuclear envelope organization	1	991.3×	0.002	LMNB2
nuclear migration	1	732.7×	0.002	LMNB2
heterochromatin formation	1	255.3×	0.004	LMNB2

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
LMNB2	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
LMNB2	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	LMNB2

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)
LMNB2	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.