Lipodystrophy

Summary

Lipodystrophy (MONDO:0006573) is a disease (an umbrella term covering 5 Mondo subtypes) caused by BSCL2 (GenCC Strong), with 5 cohort genes and 81 clinical trials. Top therapeutic interventions include metreleptin, pravastatin, and abacavir.

At a glance

• Causal gene: BSCL2 (GenCC Strong)
• Umbrella term: 5 Mondo subtypes
• Cohort genes: 5
• ClinVar variants: 10
• Clinical trials: 81

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	lipodystrophy
Mondo ID	MONDO:0006573
EFO	EFO:1000727
MeSH	D008060
DOID	DOID:811
NCIT	C97093
SNOMED CT	71325002
UMLS	C0023787
MedGen	6111
GARD	0027051
Is cancer (heuristic)	no

Also known as: lipodsystrophic syndrome · lipodsystrophic syndromes · lipodystrophy · lipodystrophy (disease)

Data availability: 10 ClinVar variants · 4 GenCC gene-disease records · 1 HPO phenotype.

Disease family

An umbrella term covering 5 Mondo subtypes.

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

Related subtypes (36): glutaric aciduria, mineral metabolism disease, xanthinuria, chondrocalcinosis, ochronosis disorder, glucose metabolism disease, diabetic kidney disease, xanthoma, diabetic retinopathy, hypertriglyceridemia, gout, lactic acidosis, acquired metabolic disease, developmental anomaly of metabolic origin, dopa-responsive dystonia, hypoalphalipoproteinemia, steroid dehydrogenase deficiency-dental anomalies syndrome, inborn errors of metabolism, vitamin B12 deficiency, proteostasis deficiencies, hyperlipidemia, disorder of GPI anchor biosynthesis, bilirubin metabolism disease, hyperlipoproteinemia, carbohydrate metabolism disease, porphyrin metabolism disease, purine metabolism disease, amino acid metabolism disease, pyrimidine metabolism disease, disorder of acid-base balance, disorder of glutamate decarboxylase, tumor lysis syndrome, collagenous sprue, steroid metabolism disease, disorder of organic acid metabolism, skeletal fluorosis

Subtypes (5): localized lipodystrophy, hereditary lipodystrophy, acquired lipodystrophy, generalized lipodystrophy, partial 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

10 retrieved; paginated sample, class counts are floors:

4 pathogenic/likely pathogenic, 2 conflicting classifications of pathogenicity, 2 uncertain significance, 1 benign, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
424623	NM_001122955.4(BSCL2):c.844_854del (p.Ala282fs)	BSCL2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
66952	NM_170707.4(LMNA):c.898G>A (p.Asp300Asn)	LMNA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
66888	NM_170707.4(LMNA):c.29C>T (p.Thr10Ile)	LOC129931597	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
8136	NM_138711.6(PPARG):c.1394C>T (p.Pro465Leu)	PPARG	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3383977	NM_001122955.4(BSCL2):c.825dup (p.Ala276fs)	BSCL2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
246599	NM_001122955.4(BSCL2):c.448G>A (p.Val150Ile)	BSCL2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
163878	NM_170707.4(LMNA):c.1634G>A (p.Arg545His)	LMNA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
289075	NM_001122955.4(BSCL2):c.968G>T (p.Trp323Leu)	BSCL2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2175684	NM_138711.6(PPARG):c.1140C>A (p.Ser380Arg)	PPARG	Uncertain significance	criteria provided, multiple submitters, no conflicts
128533	NM_001122955.4(BSCL2):c.1137A>G (p.Glu379=)	BSCL2	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 20 · Orphanet: 30 · 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
BSCL2	Definitive	Autosomal recessive	congenital generalized lipodystrophy type 2	16
ADRA2A	Limited	Autosomal dominant	lipodystrophy	2
SUPT7L	Limited	Autosomal recessive	lipodystrophy	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BSCL2	Orphanet:100998	Autosomal dominant spastic paraplegia type 17
BSCL2	Orphanet:139536	Distal hereditary motor neuropathy type 5
BSCL2	Orphanet:363400	Progressive encephalopathy-severe neurodegeneration-lipodystrophy syndrome
BSCL2	Orphanet:696289	Congenital generalized lipodystrophy type 2
LMNA	Orphanet:154	Familial isolated dilated cardiomyopathy
LMNA	Orphanet:157973	Congenital muscular dystrophy due to LMNA mutation
LMNA	Orphanet:1662	Restrictive dermopathy
LMNA	Orphanet:168796	Heart-hand syndrome, Slovenian type
LMNA	Orphanet:2229	Dilated cardiomyopathy-hypergonadotropic hypogonadism syndrome
LMNA	Orphanet:2348	Familial partial lipodystrophy, Dunnigan type
LMNA	Orphanet:280365	Autosomal semi-dominant severe lipodystrophic laminopathy
LMNA	Orphanet:293888	Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant
LMNA	Orphanet:293899	Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant
LMNA	Orphanet:293910	Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant
LMNA	Orphanet:300751	Familial dilated cardiomyopathy with conduction defect due to LMNA mutation
LMNA	Orphanet:363618	LMNA-related cardiocutaneous progeria syndrome
LMNA	Orphanet:54260	Left ventricular noncompaction
LMNA	Orphanet:675396	Epithelioid hemangioma
LMNA	Orphanet:740	Hutchinson-Gilford progeria syndrome
LMNA	Orphanet:79084	Familial partial lipodystrophy, Köbberling type
LMNA	Orphanet:79474	Atypical Werner syndrome
LMNA	Orphanet:90153	Mandibuloacral dysplasia with type A lipodystrophy
LMNA	Orphanet:98853	Autosomal dominant Emery-Dreifuss muscular dystrophy
LMNA	Orphanet:98855	Autosomal recessive Emery-Dreifuss muscular dystrophy
LMNA	Orphanet:98856	Charcot-Marie-Tooth disease type 2B1
PPARG	Orphanet:146	Differentiated thyroid carcinoma
PPARG	Orphanet:251576	Gliosarcoma
PPARG	Orphanet:251579	Giant cell glioblastoma
PPARG	Orphanet:696242	PPARG-associated congenital generalized lipodystrophy
PPARG	Orphanet:79083	PPARG-related familial partial lipodystrophy

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BSCL2	HGNC:15832	ENSG00000168000	Q96G97	Seipin	gencc,clinvar
ADRA2A	HGNC:281	ENSG00000150594	P08913	Alpha-2A adrenergic receptor	gencc
SUPT7L	HGNC:30632	ENSG00000119760	O94864	STAGA complex 65 subunit gamma	gencc
LMNA	HGNC:6636	ENSG00000160789	P02545	Prelamin-A/C	clinvar
PPARG	HGNC:9236	ENSG00000132170	P37231	Peroxisome proliferator-activated receptor gamma	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BSCL2	Seipin	Plays a crucial role in the formation of lipid droplets (LDs) which are storage organelles at the center of lipid and energy homeostasis.
ADRA2A	Alpha-2A adrenergic receptor	Alpha-2 adrenergic receptors are G protein-coupled receptors for catecholamines that activate the G(i/o) protein pathway, thereby promoting adenylyl cyclase inhibition, ERK1/2 stimulation, and voltage-gated calcium channels suppression.
LMNA	Prelamin-A/C	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.
PPARG	Peroxisome proliferator-activated receptor gamma	Ligand-activated transcription factor that forms obligate heterodimers with the retinoic acid receptor and acts as a key regulator of biological processes, such as adipocyte differentiation, lipid metabolism, glucose homeostasis and beta-o…

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 3 · Druggable fraction: 0.4

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
Nuclear receptor	1	77.2×	0.039
GPCR	1	4.8×	0.288
Other/Unknown	3	1.1×	0.608

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BSCL2	Other/Unknown	no		Seipin
ADRA2A	GPCR	yes		GPCR_Rhodpsn, ADRA2A_rcpt, ADR_fam
SUPT7L	Other/Unknown	no		BTP, Histone-fold, SUPT7L/Spt7
LMNA	Other/Unknown	no		Lamin_tail_dom, IF_conserved, Lamin_tail_dom_sf
PPARG	Nuclear receptor	yes		Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt, Nuclear_hrmn_rcpt

Expression context

Cohort genes with no expression data: 0.

5 cohort genes 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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
pituitary gland	1
primary visual cortex	1
superior frontal gyrus	1
cortical plate	1
endocervix	1
subcutaneous adipose tissue	1
adenohypophysis	1
middle temporal gyrus	1
right uterine tube	1
mucosa of stomach	1
nipple	1
skin of abdomen	1
adipose tissue of abdominal region	1
omental fat pad	1
peritoneum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BSCL2	149	ubiquitous	marker	superior frontal gyrus, primary visual cortex, pituitary gland
ADRA2A	234	broad	marker	cortical plate, subcutaneous adipose tissue, endocervix
SUPT7L	289	ubiquitous	marker	middle temporal gyrus, right uterine tube, adenohypophysis
LMNA	295	ubiquitous	marker	nipple, mucosa of stomach, skin of abdomen
PPARG	194	ubiquitous	marker	omental fat pad, peritoneum, adipose tissue of abdominal region

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PPARG	7,747
LMNA	7,173
BSCL2	1,503
SUPT7L	1,331
ADRA2A	1,246

Intra-cohort edges

A	B	Sources
BSCL2	LMNA	string_interaction

Structural data

PDB: 5 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PPARG	P37231	380
LMNA	P02545	28
ADRA2A	P08913	19
SUPT7L	O94864	4
BSCL2	Q96G97	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 45. Enrichment computed across 5 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Breakdown of the nuclear lamina	1	951.7×	0.024	LMNA
Adrenaline signalling through Alpha-2 adrenergic receptor	1	951.7×	0.024	ADRA2A
MECP2 regulates transcription factors	1	571.0×	0.026	PPARG
Adrenoceptors	1	317.2×	0.033	ADRA2A
Depolymerization of the Nuclear Lamina	1	190.3×	0.033	LMNA
Initiation of Nuclear Envelope (NE) Reformation	1	150.3×	0.033	LMNA
IRE1alpha activates chaperones	1	129.8×	0.033	LMNA
Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer’s disease models	1	129.8×	0.033	LMNA
Nuclear Envelope Breakdown	1	114.2×	0.033	LMNA
Platelet Aggregation (Plug Formation)	1	109.8×	0.033	ADRA2A
Adrenaline,noradrenaline inhibits insulin secretion	1	98.5×	0.033	ADRA2A
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2	1	95.2×	0.033	PPARG
Surfactant metabolism	1	92.1×	0.033	ADRA2A
Unfolded Protein Response (UPR)	1	89.2×	0.033	LMNA
Amine ligand-binding receptors	1	86.5×	0.033	ADRA2A
SUMOylation of intracellular receptors	1	84.0×	0.033	PPARG
Oncogenic MAPK signaling	1	62.1×	0.041	LMNA
G alpha (z) signalling events	1	58.3×	0.041	ADRA2A
Regulation of insulin secretion	1	54.9×	0.041	ADRA2A
XBP1(S) activates chaperone genes	1	53.9×	0.041	LMNA
Nuclear Receptor transcription pathway	1	50.1×	0.042	PPARG
Regulation of PTEN gene transcription	1	44.6×	0.044	PPARG
Integration of energy metabolism	1	43.9×	0.044	ADRA2A
Signaling by BRAF and RAF1 fusions	1	42.6×	0.044	LMNA
Meiotic synapsis	1	35.2×	0.051	LMNA
Transcriptional regulation of white adipocyte differentiation	1	32.4×	0.053	PPARG
Platelet activation, signaling and aggregation	1	26.4×	0.062	ADRA2A
PPARA activates gene expression	1	23.6×	0.067	PPARG
MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis	1	20.7×	0.072	PPARG
Chromatin organization	1	20.4×	0.072	SUPT7L

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of cardiac muscle hypertrophy in response to stress	2	749.0×	4e-04	LMNA, PPARG
negative regulation of lipid catabolic process	2	337.0×	9e-04	BSCL2, ADRA2A
negative regulation of uterine smooth muscle contraction	1	3370.4×	0.009	ADRA2A
phospholipase C-activating adrenergic receptor signaling pathway	1	1685.2×	0.009	ADRA2A
negative regulation of connective tissue replacement involved in inflammatory response wound healing	1	1685.2×	0.009	PPARG
positive regulation of adiponectin secretion	1	1123.5×	0.009	PPARG
beige fat cell differentiation	1	1123.5×	0.009	PPARG
DNA double-strand break attachment to nuclear envelope	1	1123.5×	0.009	LMNA
establishment or maintenance of microtubule cytoskeleton polarity	1	842.6×	0.009	LMNA
thermoception	1	842.6×	0.009	ADRA2A
negative regulation of extracellular matrix assembly	1	842.6×	0.009	PPARG
negative regulation of cellular response to transforming growth factor beta stimulus	1	842.6×	0.009	PPARG
negative regulation of epinephrine secretion	1	674.1×	0.009	ADRA2A
positive regulation of lipid metabolic process	1	674.1×	0.009	PPARG
positive regulation of fatty acid metabolic process	1	674.1×	0.009	PPARG
nuclear pore localization	1	674.1×	0.009	LMNA
adenylate cyclase-inhibiting adrenergic receptor signaling pathway	1	674.1×	0.009	ADRA2A
negative regulation of mitochondrial fission	1	674.1×	0.009	PPARG
positive regulation of lipoprotein transport	1	674.1×	0.009	PPARG
negative regulation of receptor signaling pathway via STAT	1	674.1×	0.009	PPARG
negative regulation of vascular endothelial cell proliferation	1	674.1×	0.009	PPARG
fat cell differentiation	2	72.5×	0.009	BSCL2, PPARG
glucose homeostasis	2	52.2×	0.009	ADRA2A, PPARG
cellular response to hypoxia	2	48.5×	0.009	LMNA, PPARG
negative regulation of norepinephrine secretion	1	561.7×	0.009	ADRA2A
fear response	1	561.7×	0.009	ADRA2A
negative regulation of mesenchymal cell proliferation	1	561.7×	0.009	LMNA
positive regulation of cholesterol transport	1	481.5×	0.010	PPARG
response to lipid	1	481.5×	0.010	PPARG
positive regulation of potassium ion transport	1	421.3×	0.010	ADRA2A

Therapeutics

Drugs indicated for this disease

1 approved, 1 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Metreleptin	Approved (phase 4)
Fenofibrate	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Abacavir.

Drug target analysis

Approved (phase 4): 3 · Phase ≥3: 3 · Phased (≥1): 3 · Undrugged: 2

Druggability breadth: 3 of 5 evidence-associated genes (60%) 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
ADRA2A	CANDESARTAN CILEXETIL
LMNA	BEPRIDIL
PPARG	METHYLENE BLUE ANHYDROUS

Top cohort targets by molecule count

Symbol	Molecules	Max phase
LMNA	823	4
ADRA2A	418	4
PPARG	83	4
BSCL2	0	0
SUPT7L	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CANDESARTAN CILEXETIL	4	ADRA2A, PPARG
TELMISARTAN	4	ADRA2A, PPARG
BEXAROTENE	4	ADRA2A, PPARG
CLOTRIMAZOLE	4	ADRA2A, LMNA
METHYSERGIDE	4	ADRA2A
TIZANIDINE	4	ADRA2A, LMNA
ACETOPHENAZINE	4	ADRA2A
MESORIDAZINE	4	ADRA2A
PHENELZINE	4	ADRA2A, LMNA
EPINASTINE	4	ADRA2A
DROPERIDOL	4	ADRA2A, LMNA
ARIPIPRAZOLE	4	ADRA2A
AMOXAPINE	4	ADRA2A, LMNA
NORETHINDRONE	4	ADRA2A
DESLORATADINE	4	ADRA2A, LMNA
TETRABENAZINE	4	ADRA2A
PALONOSETRON	4	ADRA2A
DIETHYLPROPION	4	ADRA2A
TIZANIDINE HYDROCHLORIDE	4	ADRA2A
DIMENHYDRINATE	4	ADRA2A, LMNA
NEFAZODONE HYDROCHLORIDE	4	ADRA2A, LMNA
GUANFACINE HYDROCHLORIDE	4	ADRA2A
DIHYDROERGOTAMINE MESYLATE	4	ADRA2A, LMNA
OXYMETAZOLINE HYDROCHLORIDE	4	ADRA2A, LMNA
AZELASTINE HYDROCHLORIDE	4	ADRA2A, LMNA
THIOTHIXENE	4	ADRA2A
BENZTHIAZIDE	4	ADRA2A
CABERGOLINE	4	ADRA2A
SERTACONAZOLE	4	ADRA2A
BENZTROPINE	4	ADRA2A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
PPARG	2,033	Binding:1593, Functional:380, ADMET:56, Toxicity:3, Unclassified:1
ADRA2A	896	Binding:687, Functional:190, ADMET:17, Unclassified:2
LMNA	12	Binding:9, Functional:3

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
ADRA2A	896
PPARG	2,033

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

30 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)
CANDESARTAN CILEXETIL	4	ADRA2A, PPARG
TELMISARTAN	4	ADRA2A, PPARG
BEXAROTENE	4	ADRA2A, PPARG
CLOTRIMAZOLE	4	ADRA2A, LMNA
METHYSERGIDE	4	ADRA2A
TIZANIDINE	4	ADRA2A, LMNA
ACETOPHENAZINE	4	ADRA2A
MESORIDAZINE	4	ADRA2A
PHENELZINE	4	ADRA2A, LMNA
EPINASTINE	4	ADRA2A
DROPERIDOL	4	ADRA2A, LMNA
ARIPIPRAZOLE	4	ADRA2A
AMOXAPINE	4	ADRA2A, LMNA
NORETHINDRONE	4	ADRA2A
DESLORATADINE	4	ADRA2A, LMNA
TETRABENAZINE	4	ADRA2A
PALONOSETRON	4	ADRA2A
DIETHYLPROPION	4	ADRA2A
TIZANIDINE HYDROCHLORIDE	4	ADRA2A
DIMENHYDRINATE	4	ADRA2A, LMNA
NEFAZODONE HYDROCHLORIDE	4	ADRA2A, LMNA
GUANFACINE HYDROCHLORIDE	4	ADRA2A
DIHYDROERGOTAMINE MESYLATE	4	ADRA2A, LMNA
OXYMETAZOLINE HYDROCHLORIDE	4	ADRA2A, LMNA
AZELASTINE HYDROCHLORIDE	4	ADRA2A, LMNA
THIOTHIXENE	4	ADRA2A
BENZTHIAZIDE	4	ADRA2A
CABERGOLINE	4	ADRA2A
SERTACONAZOLE	4	ADRA2A
BENZTROPINE	4	ADRA2A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	ADRA2A, LMNA, PPARG
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	2	BSCL2, SUPT7L

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
BSCL2	0	LMNA
SUPT7L	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 81.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	47
PHASE2	12
PHASE4	10
PHASE3	6
PHASE1	5
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00005764	PHASE4	COMPLETED	A Study of Increased Lactic Acid and Abnormal Fat Distribution in HIV-Positive Patients
NCT00006190	PHASE4	COMPLETED	A Study to Determine How and Why HIV-Infected Subjects on Anti-viral Treatment Develop Lipodystrophy
NCT00119769	PHASE4	COMPLETED	The Effect of Low-Dose Human Growth Hormone Therapy in HIV Infected Patients
NCT00192621	PHASE4	COMPLETED	Seronegatives and Metabolic Abnormalities Protocol 2 (SAMA002): Study to Compare the Effect of Kaletra and Combivir® in HIV-Negative Healthy Subjects
NCT00202228	PHASE4	COMPLETED	Lactate Metabolism Study in HIV Infected Persons
NCT00227500	PHASE4	COMPLETED	Pravastatin for Hyperlipidaemia in HIV.
NCT00360139	PHASE4	WITHDRAWN	Clinical Trial to Determine the Efficacy of Sculptra™ Dermal Filler for the Correction of Contour Deformities Caused by Lipoatrophy
NCT00426296	PHASE4	UNKNOWN	SHARE: Simple HAART With Abacavir, Reyataz, and Epivir
NCT00865007	PHASE4	COMPLETED	Lopinavir/r Monotherapy Versus Abacavir/Lamivudine and Lopinavir/r for Limb Fat Recovery in Persons With Lipoatrophy
NCT01612858	PHASE4	COMPLETED	Metabolic Abnormalities in HIV-infected Persons
NCT02262832	PHASE3	ACTIVE_NOT_RECRUITING	Compassionate Use of Metreleptin in Previously Treated People With Generalized Lipodystrophy
NCT00006412	PHASE3	COMPLETED	Safety and Effectiveness of Fenofibrate and Pravastatin in HIV-Positive Patients With Abnormal Blood Lipids
NCT00082628	PHASE3	COMPLETED	Treatment of Abnormal Adipose Tissue Accumulation in Human Immunodeficiency Virus (HIV) Patients
NCT00123253	PHASE3	COMPLETED	TH9507 in Patients With HIV-Associated Lipodystrophy
NCT00608023	PHASE3	COMPLETED	TH9507 Extension Study in Patients With HIV-Associated Lipodystrophy
NCT00910936	PHASE2/PHASE3	UNKNOWN	Exercise for Patients With HIV Infections
NCT04860063	PHASE3	UNKNOWN	Effect of Berberine on Metabolic Syndrome, Efficacy and Safety in Combination With Antiretroviral Therapy in PLWH.
NCT02262806	PHASE2	ACTIVE_NOT_RECRUITING	Compassionate Use of Metreleptin in Previously Treated People With Partial Lipodystrophy
NCT07313787	PHASE2	NOT_YET_RECRUITING	Effects of Meal Macronutrients on Postprandial Lipids
NCT00005905	PHASE2	COMPLETED	Leptin to Treat Lipodystrophy
NCT00021463	PHASE2	COMPLETED	Changing to Nonprotease Inhibitor Treatment to Improve Side Effects
NCT00025883	PHASE2	COMPLETED	Leptin to Treat Lipodystrophy
NCT00119379	PHASE2	COMPLETED	Effectiveness of Nucleoside Supplementation or Switch to Tenofovir in Reversing Fat Loss in HIV Infected Adults
NCT00461552	PHASE2	COMPLETED	Therapeutic Approaches to HAART-Induced Lipodystrophy
NCT00647946	PHASE2	COMPLETED	Study to Evaluate Changes in Limb Fat When Switching From a Thymidine Analogue
NCT00656175	PHASE2	COMPLETED	Raltegravir Therapy for Women With HIV and Fat Accumulation
NCT01679197	PHASE2	COMPLETED	Clinical Protocol to Investigate the Efficacy of Recombinant Human Leptin (Metreleptin) in Nonalcoholic Steatohepatitis (NASH) or Nonalcoholic Fatty Liver Disease (NAFLD) Associated With Lipodystrophy
NCT01778556	PHASE2	COMPLETED	Short-term Effects of Leptin in People With Lipodystrophy
NCT02639286	PHASE2	COMPLETED	Efficacy, Safety and Tolerability of ISIS 304801 in People With Partial Lipodystrophy With an Open-Label Extension
NCT00006185	PHASE1	COMPLETED	Underlying Abnormalities in Fat and Muscle Leading to Lipodystrophy Syndrome
NCT00017758	PHASE1	COMPLETED	The Effect of Efavirenz and Nelfinavir on the Blood Levels of Certain Lipid-Lowering Drugs
NCT00715546	PHASE1	UNKNOWN	Autologous Adipose-Derived Stem Cell Transplantation in Patients With Lipodystrophy
NCT02034786	PHASE1	UNKNOWN	Safety Study of Filler Agent Composed of Autologous Mesenchymal Stem Cells and Hyaluronic Acid
NCT02647853	PHASE1	COMPLETED	Phase 1 Study to Assess the Safety and Tolerability of TAT4 Gel in Healthy Volunteers
NCT03087253	Not specified	RECRUITING	The LD Lync Study - Natural History Study of Lipodystrophy Syndromes
NCT03900286	Not specified	RECRUITING	Low Energy Diet and Familial Partial Lipodystrophy
NCT04710056	Not specified	AVAILABLE	Expanded Access to REGN4461 for Patients With Diseases Associated With Deficient Leptin Signaling
NCT05419037	Not specified	RECRUITING	Natural History of Pregnancy and Pregnancy Outcomes in Metreleptin-Treated vs Untreated Subjects With Lipodystrophy
NCT05789251	Not specified	RECRUITING	Assess the Possibility of Diagnosing Diabetes and Rediabetes Following Oral Induced Hyperglycemia in Patients With Dunnigan’s Partial Familial Lipodystrophy by Replacing 75 g of Glucose With a Standardized Carbohydrate Breakfast and Continuous Interstitial Monitoring Glucose)
NCT05996536	Not specified	RECRUITING	Feasibility of Adipose Tissue Triglyceride (TG) Labelling in Familial Partial Lipodystrophy (FPLD)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
METRELEPTIN	4	6
PRAVASTATIN	4	5
ABACAVIR	4	4
LAMIVUDINE	4	4
TENOFOVIR DISOPROXIL	4	4
TESAMORELIN	4	4
BERBERINE	4	3
VOLANESORSEN	4	3
NELFINAVIR MESYLATE	4	2
ATAZANAVIR	4	1
ATORVASTATIN	4	1
EFAVIRENZ	4	1
FENOFIBRATE	4	1
NEVIRAPINE	4	1
PIOGLITAZONE	4	1
RALTEGRAVIR	4	1
RIBOFLAVIN	4	1
RITONAVIR	4	1
STAVUDINE	4	1
ZIDOVUDINE	4	1
MIBAVADEMAB	2	1
CHEMBL18314	0	3
CHEMBL365442	0	2
CHEMBL4076715	0	2
CHEMBL26318	0	1
CHEMBL207216	0	1
CHEMBL418334	0	1
CHEMBL511565	0	1
CHEMBL5267279	0	1
CHEMBL4454249	0	1