Berardinelli-Seip congenital lipodystrophy

Summary

Berardinelli-Seip congenital lipodystrophy (MONDO:0018883) is a disease with 7 cohort genes.

At a glance

• Prevalence: 1-9 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 7
• ClinVar variants: 34
• Phenotypes (HPO): 37

Clinical features

Epidemiology

Prevalence records

10 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 1 000 000	0.6812	Worldwide	Validated
Point prevalence	1-9 / 1 000 000	0.5	Europe	Validated
Point prevalence	<1 / 1 000 000	0.01	United States	Validated
Point prevalence	1-9 / 1 000 000	0.86	Peru	Validated
Point prevalence	1-9 / 1 000 000	0.1	Norway	Validated
Point prevalence	1-9 / 1 000 000	0.5	Lebanon	Validated
Point prevalence	1-9 / 1 000 000	0.2	Portugal	Validated
Point prevalence	<1 / 1 000 000	0.05	Turkey	Validated
Point prevalence	1-9 / 100 000	3.23	Brazil	Validated
Prevalence at birth	1-9 / 100 000	4	Oman	Validated

Signs & symptoms

Clinical features (HPO)

37 HPO clinical features (Orphanet curated; top 37 by frequency):

HPO ID	Term	Frequency
HP:0000855	Insulin resistance	Very frequent (80-99%)
HP:0002240	Hepatomegaly	Very frequent (80-99%)
HP:0003712	Skeletal muscle hypertrophy	Very frequent (80-99%)
HP:0008887	Adipose tissue loss	Very frequent (80-99%)
HP:0009125	Lipodystrophy	Very frequent (80-99%)
HP:0000819	Diabetes mellitus	Frequent (30-79%)
HP:0000998	Hypertrichosis	Frequent (30-79%)
HP:0001249	Intellectual disability	Frequent (30-79%)
HP:0002155	Hypertriglyceridemia	Frequent (30-79%)
HP:0000158	Macroglossia	Occasional (5-29%)
HP:0000294	Low anterior hairline	Occasional (5-29%)
HP:0000303	Mandibular prognathia	Occasional (5-29%)
HP:0000336	Prominent supraorbital ridges	Occasional (5-29%)
HP:0000842	Hyperinsulinemia	Occasional (5-29%)
HP:0000956	Acanthosis nigricans	Occasional (5-29%)
HP:0001015	Prominent superficial veins	Occasional (5-29%)
HP:0001176	Large hands	Occasional (5-29%)
HP:0001263	Global developmental delay	Occasional (5-29%)
HP:0001394	Cirrhosis	Occasional (5-29%)
HP:0001397	Hepatic steatosis	Occasional (5-29%)
HP:0001508	Failure to thrive	Occasional (5-29%)
HP:0001635	Congestive heart failure	Occasional (5-29%)
HP:0001639	Hypertrophic cardiomyopathy	Occasional (5-29%)
HP:0001833	Long foot	Occasional (5-29%)
HP:0001999	Abnormal facial shape	Occasional (5-29%)
HP:0002162	Low posterior hairline	Occasional (5-29%)
HP:0003124	Hypercholesterolemia	Occasional (5-29%)
HP:0003247	Overgrowth of external genitalia	Occasional (5-29%)
HP:0005616	Accelerated skeletal maturation	Occasional (5-29%)
HP:0008665	Clitoral hypertrophy	Occasional (5-29%)
HP:0011407	Proportionate tall stature	Occasional (5-29%)
HP:0012062	Bone cyst	Occasional (5-29%)
HP:0030796	Increased C-peptide level	Occasional (5-29%)
HP:0000141	Amenorrhea	Very rare (<1-4%)
HP:0000147	Polycystic ovaries	Very rare (<1-4%)
HP:0000876	Oligomenorrhea	Very rare (<1-4%)
HP:0010465	Precocious puberty in females	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Berardinelli-Seip congenital lipodystrophy
Mondo ID	MONDO:0018883
Orphanet	528
ICD-11	1628738474, 641763399
NCIT	C84594
GARD	0013388
MedDRA	10024603
Is cancer (heuristic)	no

Also known as: Beradinelli-Seip syndrome · Berardinelli lipodystrophy syndrome · Berardinelli Seip syndrome · Brunzell syndrome · BSCL · congenital generalised lipodystrophy · GCL · generalised congenital lipodystrophy · generalized congenital lipodystrophy · Seip-Bernardinelli syndrome · total lipodystrophy

Data availability: 34 ClinVar variants · 6 GenCC gene-disease records.

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › lipodystrophy › hereditary lipodystrophy › Berardinelli-Seip congenital lipodystrophy

Related subtypes (10): congenital generalized lipodystrophy, lipodystrophy due to peptidic growth factors deficiency, Wiedemann-Rautenstrauch syndrome, SHORT syndrome, lipodystrophy-intellectual disability-deafness syndrome, Keppen-Lubinsky syndrome, severe neurodegenerative syndrome with lipodystrophy, lipoatrophy with diabetes, leukomelanodermic papules, liver steatosis, and hypertrophic cardiomyopathy, mandibuloacral dysplasia, familial partial lipodystrophy

Subtypes (4): congenital generalized lipodystrophy type 2, congenital generalized lipodystrophy type 1, congenital generalized lipodystrophy type 3, PPARG-associated congenital 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

34 retrieved; paginated sample, class counts are floors:

13 pathogenic, 12 uncertain significance, 6 conflicting classifications of pathogenicity, 3 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
143858	NM_001122955.4(BSCL2):c.985C>T (p.Arg329Ter)	BSCL2	Pathogenic	criteria provided, multiple submitters, no conflicts
372117	NM_001122955.4(BSCL2):c.766-2A>G	BSCL2	Pathogenic	criteria provided, single submitter
372120	NM_001122955.4(BSCL2):c.974dup (p.Ile326fs)	BSCL2	Pathogenic	criteria provided, multiple submitters, no conflicts
424623	NM_001122955.4(BSCL2):c.844_854del (p.Ala282fs)	BSCL2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4532	NM_001122955.4(BSCL2):c.493_494insAA (p.Met165fs)	BSCL2	Pathogenic	criteria provided, single submitter
4535	NM_001122955.4(BSCL2):c.509_513del (p.Tyr170fs)	BSCL2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4536	NM_001122955.4(BSCL2):c.517dup (p.Thr173fs)	BSCL2	Pathogenic	criteria provided, multiple submitters, no conflicts
4537	NM_001122955.4(BSCL2):c.604C>T (p.Arg202Ter)	BSCL2	Pathogenic	criteria provided, multiple submitters, no conflicts
4540	NM_001122955.4(BSCL2):c.828del (p.Tyr277fs)	BSCL2	Pathogenic	criteria provided, multiple submitters, no conflicts
4543	NM_001122955.4(BSCL2):c.455A>G (p.Asn152Ser)	BSCL2	Pathogenic	criteria provided, multiple submitters, no conflicts
4544	NM_001122955.4(BSCL2):c.461C>T (p.Ser154Leu)	BSCL2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4545	NM_001122955.4(BSCL2):c.1015C>T (p.Arg339Ter)	BSCL2	Pathogenic	criteria provided, single submitter
4546	NM_001122955.4(BSCL2):c.757G>T (p.Glu253Ter)	BSCL2	Pathogenic	criteria provided, multiple submitters, no conflicts
476810	NM_001122955.4(BSCL2):c.461C>G (p.Ser154Trp)	BSCL2	Pathogenic	criteria provided, multiple submitters, no conflicts
372119	NM_001122955.4(BSCL2):c.864-2A>G	HNRNPUL2-BSCL2	Pathogenic	criteria provided, single submitter
4539	NM_001122955.4(BSCL2):c.826G>C (p.Ala276Pro)	HNRNPUL2-BSCL2	Pathogenic	criteria provided, multiple submitters, no conflicts
1418830	NM_001122955.4(BSCL2):c.405-11A>G	BSCL2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
143859	NM_001122955.4(BSCL2):c.538G>T (p.Glu180Ter)	BSCL2	Conflicting classifications of pathogenicity	no assertion criteria provided
4531	NM_001122955.4(BSCL2):c.384_385delinsGGA (p.Ser128fs)	BSCL2	Conflicting classifications of pathogenicity	no assertion criteria provided
4533	NM_001122955.4(BSCL2):c.507_508del (p.Tyr170fs)	BSCL2	Conflicting classifications of pathogenicity	no assertion criteria provided
4538	NM_001122955.4(BSCL2):c.630+1G>A	BSCL2	Conflicting classifications of pathogenicity	no assertion criteria provided
4542	NM_001122955.4(BSCL2):c.864-3C>G	BSCL2	Conflicting classifications of pathogenicity	no assertion criteria provided
2571522	NM_001122955.4(BSCL2):c.299G>A (p.Cys100Tyr)	BSCL2	Uncertain significance	no assertion criteria provided
2571523	NM_001122955.4(BSCL2):c.358_376del (p.Tyr120fs)	BSCL2	Uncertain significance	no assertion criteria provided
2571525	NM_001122955.4(BSCL2):c.464T>C (p.Leu155Pro)	BSCL2	Uncertain significance	no assertion criteria provided
2571526	NM_001122955.4(BSCL2):c.529G>T (p.Glu177Ter)	BSCL2	Uncertain significance	no assertion criteria provided
2571529	NM_001122955.4(BSCL2):c.631-2A>C	BSCL2	Uncertain significance	no assertion criteria provided
2571530	NM_001122955.4(BSCL2):c.752A>G (p.Tyr251Cys)	BSCL2	Uncertain significance	no assertion criteria provided
2571531	NM_001122955.4(BSCL2):c.876C>G (p.Tyr292Ter)	BSCL2	Uncertain significance	no assertion criteria provided
372115	NM_001122955.4(BSCL2):c.346_347dup (p.Tyr117fs)	BSCL2	Uncertain significance	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 39 · Orphanet: 16 · 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
AGPAT2	Definitive	Autosomal recessive	congenital generalized lipodystrophy type 1	5
BSCL2	Definitive	Autosomal recessive	congenital generalized lipodystrophy type 2	16
PPARG	Definitive	Autosomal dominant	PPARG-related familial partial lipodystrophy	7
CAV1	Strong	Autosomal dominant	partial lipodystrophy, congenital cataracts, and neurodegeneration syndrome	7
CAVIN1	Strong	Autosomal recessive	congenital generalized lipodystrophy type 4	3
FOS	Supportive	Autosomal recessive	Berardinelli-Seip congenital lipodystrophy

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
CAV1	Orphanet:220393	Diffuse cutaneous systemic sclerosis
CAV1	Orphanet:220402	Limited cutaneous systemic sclerosis
CAV1	Orphanet:275777	Heritable pulmonary arterial hypertension
CAV1	Orphanet:696206	Congenital generalized lipodystrophy type 3
AGPAT2	Orphanet:696189	Congenital generalized lipodystrophy type 1
FOS	Orphanet:675396	Epithelioid hemangioma
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
CAVIN1	Orphanet:228429	Congenital generalized lipodystrophy type 4

Cohort genes → proteins

7 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	7

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BSCL2	HGNC:15832	ENSG00000168000	Q96G97	Seipin	gencc,clinvar
CAV1	HGNC:1527	ENSG00000105974	Q03135	Caveolin-1	gencc
AGPAT2	HGNC:325	ENSG00000169692	O15120	1-acyl-sn-glycerol-3-phosphate acyltransferase beta	gencc
FOS	HGNC:3796	ENSG00000170345	P01100	Protein c-Fos	gencc
PPARG	HGNC:9236	ENSG00000132170	P37231	Peroxisome proliferator-activated receptor gamma	gencc
CAVIN1	HGNC:9688	ENSG00000177469	Q6NZI2	Caveolae-associated protein 1	gencc
HNRNPUL2-BSCL2	HGNC:49189	ENSG00000234857		HNRNPUL2-BSCL2 readthrough (NMD candidate)	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.
CAV1	Caveolin-1	May act as a scaffolding protein within caveolar membranes.
AGPAT2	1-acyl-sn-glycerol-3-phosphate acyltransferase beta	Converts 1-acyl-sn-glycerol-3-phosphate (lysophosphatidic acid or LPA) into 1,2-diacyl-sn-glycerol-3-phosphate (phosphatidic acid or PA) by incorporating an acyl moiety at the sn-2 position of the glycerol backbone.
FOS	Protein c-Fos	Nuclear phosphoprotein which forms a tight but non-covalently linked complex with the JUN/AP-1 transcription factor.
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…
CAVIN1	Caveolae-associated protein 1	Plays an important role in caveolae formation and organization.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 5 · Druggable fraction: 0.29

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	55.1×	0.054
Enzyme (other)	1	1.7×	0.456
Other/Unknown	5	1.3×	0.456

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BSCL2	Other/Unknown	no		Seipin
CAV1	Other/Unknown	no		Caveolin, Caveolin_CS
AGPAT2	Enzyme (other)	yes	2.3.1.51	Plipid/glycerol_acylTrfase, AGP_acyltrans
FOS	Other/Unknown	no		AP-1, bZIP, bZIP_sf
PPARG	Nuclear receptor	yes		Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt, Nuclear_hrmn_rcpt
CAVIN1	Other/Unknown	no		Cavin_fam
HNRNPUL2-BSCL2	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

6 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)	7
unknown	0

Top tissues across cohort

Tissue	Cohort genes
pituitary gland	1
primary visual cortex	1
superior frontal gyrus	1
lower lobe of lung	1
parietal pleura	1
pleura	1
ileal mucosa	1
mucosa of transverse colon	1
right lobe of liver	1
gall bladder	1
mucosa of stomach	1
upper leg skin	1
adipose tissue of abdominal region	1
omental fat pad	1
peritoneum	1
popliteal artery	1
right coronary artery	1
tendon of biceps brachii	1
islet of Langerhans	1
stromal cell of endometrium	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
CAV1	287	ubiquitous	marker	parietal pleura, lower lobe of lung, pleura
AGPAT2	257	ubiquitous	marker	mucosa of transverse colon, ileal mucosa, right lobe of liver
FOS	294	ubiquitous	marker	mucosa of stomach, upper leg skin, gall bladder
PPARG	194	ubiquitous	marker	omental fat pad, peritoneum, adipose tissue of abdominal region
CAVIN1	281	ubiquitous	marker	right coronary artery, tendon of biceps brachii, popliteal artery
HNRNPUL2-BSCL2	134		yes	stromal cell of endometrium, ventricular zone, islet of Langerhans

Protein interactions among cohort

Intra-cohort edges: 7.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FOS	8,853
PPARG	7,747
CAV1	6,673
CAVIN1	2,304
AGPAT2	2,048
BSCL2	1,503
HNRNPUL2-BSCL2	0

Intra-cohort edges

A	B	Sources
AGPAT2	BSCL2	string_interaction
AGPAT2	CAV1	string_interaction
AGPAT2	CAVIN1	string_interaction
BSCL2	CAV1	string_interaction
BSCL2	CAVIN1	string_interaction
CAV1	CAVIN1	intact, string_interaction
CAV1	PPARG	biogrid_interaction

Structural data

PDB: 5 · AlphaFold-only: 1 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PPARG	P37231	380
FOS	P01100	3
CAVIN1	Q6NZI2	3
BSCL2	Q96G97	1
CAV1	Q03135	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
AGPAT2	O15120	91.66

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 80. Enrichment computed across 7 evidence-associated genes (5 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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
RHOB GTPase cycle	2	61.7×	0.018	CAV1, CAVIN1
RHOC GTPase cycle	2	58.6×	0.018	CAV1, CAVIN1
Metabolism of nitric oxide: NOS3 activation and regulation	1	456.8×	0.025	CAV1
NOSTRIN mediated eNOS trafficking	1	456.8×	0.025	CAV1
MECP2 regulates transcription factors	1	456.8×	0.025	PPARG
MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis	2	33.1×	0.025	AGPAT2, PPARG
RHOA GTPase cycle	2	29.9×	0.025	CAV1, CAVIN1
RHO GTPase cycle	2	24.0×	0.027	CAV1, CAVIN1
Activation of the AP-1 family of transcription factors	1	228.4×	0.039	FOS
eNOS activation	1	175.7×	0.039	CAV1
SARS-CoV-2 targets host intracellular signalling and regulatory pathways	1	175.7×	0.039	CAV1
Thyroxine biosynthesis	1	163.1×	0.039	CAV1
Triglyceride metabolism	1	134.3×	0.039	CAV1
FOXO-mediated transcription of cell cycle genes	1	134.3×	0.039	CAV1
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	1	134.3×	0.039	CAV1
Signaling by Rho GTPases	2	13.7×	0.039	CAV1, CAVIN1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	2	13.4×	0.039	CAV1, CAVIN1
NPAS4 regulates expression of target genes	1	99.3×	0.042	FOS
Triglyceride catabolism	1	95.2×	0.042	CAV1
Basigin interactions	1	87.8×	0.042	CAV1
Estrogen-dependent nuclear events downstream of ESR-membrane signaling	1	87.8×	0.042	FOS
VEGFR2 mediated vascular permeability	1	81.6×	0.042	CAV1
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2	1	76.1×	0.042	PPARG
Disassembly of the destruction complex and recruitment of AXIN to the membrane	1	71.4×	0.042	CAV1
FCERI mediated MAPK activation	1	69.2×	0.042	FOS
SUMOylation of intracellular receptors	1	67.2×	0.042	PPARG
FOXO-mediated transcription	1	67.2×	0.042	CAV1
RNA Polymerase I Transcription Termination	1	65.3×	0.042	CAVIN1
RHOH GTPase cycle	1	61.7×	0.042	CAV1
Synthesis of PA	1	58.6×	0.042	AGPAT2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of cholesterol efflux	2	208.1×	0.004	CAV1, PPARG
lipid storage	2	181.2×	0.004	BSCL2, CAV1
response to progesterone	2	165.2×	0.004	CAV1, FOS
negative regulation of MAPK cascade	2	100.3×	0.006	CAV1, PPARG
negative regulation of BMP signaling pathway	2	96.8×	0.006	CAV1, PPARG
positive regulation of miRNA transcription	2	96.8×	0.006	FOS, PPARG
medium-term memory	1	2808.7×	0.008	FOS
mononuclear cell differentiation	1	2808.7×	0.008	FOS
cellular response to prolactin	1	2808.7×	0.008	FOS
fat cell differentiation	2	60.4×	0.009	BSCL2, PPARG
regulation of the force of heart contraction by chemical signal	1	1404.3×	0.010	CAV1
response to forskolin	1	1404.3×	0.010	FOS
negative regulation of connective tissue replacement involved in inflammatory response wound healing	1	1404.3×	0.010	PPARG
conditioned taste aversion	1	936.2×	0.010	FOS
termination of RNA polymerase I transcription	1	936.2×	0.010	CAVIN1
intracellular nitric oxide homeostasis	1	936.2×	0.010	CAV1
insulin receptor internalization	1	936.2×	0.010	CAV1
positive regulation of adiponectin secretion	1	936.2×	0.010	PPARG
regulation of membrane repolarization during action potential	1	936.2×	0.010	CAV1
beige fat cell differentiation	1	936.2×	0.010	PPARG
protein localization to basolateral plasma membrane	1	936.2×	0.010	CAV1
positive regulation of cold-induced thermogenesis	2	54.5×	0.010	BSCL2, CAV1
cellular response to hypoxia	2	40.4×	0.010	FOS, PPARG
protein localization to plasma membrane raft	1	702.2×	0.010	CAV1
negative regulation of pinocytosis	1	702.2×	0.010	CAV1
negative regulation of extracellular matrix assembly	1	702.2×	0.010	PPARG
negative regulation of cellular response to transforming growth factor beta stimulus	1	702.2×	0.010	PPARG
skeletal muscle cell proliferation	1	561.7×	0.010	FOS
maintenance of protein location in cell	1	561.7×	0.010	CAV1
positive regulation of lipid metabolic process	1	561.7×	0.010	PPARG

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 5

Druggability breadth: 4 of 7 evidence-associated genes (57%) 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
PPARG	METHYLENE BLUE ANHYDROUS

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PPARG	83	4
FOS	1	3
BSCL2	0	0
CAV1	0	0
AGPAT2	0	0
CAVIN1	0	0
HNRNPUL2-BSCL2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
METHYLENE BLUE ANHYDROUS	4	PPARG
BENZBROMARONE	4	PPARG
BEXAROTENE	4	PPARG
PIOGLITAZONE HYDROCHLORIDE	4	PPARG
ROSIGLITAZONE MALEATE	4	PPARG
CANDESARTAN CILEXETIL	4	PPARG
TELMISARTAN	4	PPARG
RIMONABANT	4	PPARG
CEFAMANDOLE	4	PPARG
CLOBETASOL PROPIONATE	4	PPARG
ROSIGLITAZONE	4	PPARG
FULVESTRANT	4	PPARG
LIOTHYRONINE	4	PPARG
SULINDAC	4	PPARG
CEFTRIAXONE	4	PPARG
LEVOTHYROXINE	4	PPARG
CEFOTAXIME	4	PPARG
CANNABIDIOL	4	PPARG
TIPRANAVIR	4	PPARG
EFAVIRENZ	4	PPARG
PEMAFIBRATE	4	PPARG
MASOPROCOL	4	PPARG
LASOFOXIFENE	4	PPARG
ELAFIBRANOR	4	PPARG
LUMIRACOXIB	4	PPARG
TROGLITAZONE	4	PPARG
CEFTAZIDIME	4	PPARG
GEMFIBROZIL	4	PPARG
GLYBURIDE	4	PPARG
NINTEDANIB	4	PPARG

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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
FOS	11	Binding:10, Functional:1
AGPAT2	6	Binding:6
CAV1	5	Binding:5

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
AGPAT2	2.3.1.51	1-acylglycerol-3-phosphate O-acyltransferase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
PPARG	2,033

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; 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)
METHYLENE BLUE ANHYDROUS	4	PPARG
BENZBROMARONE	4	PPARG
BEXAROTENE	4	PPARG
PIOGLITAZONE HYDROCHLORIDE	4	PPARG
ROSIGLITAZONE MALEATE	4	PPARG
CANDESARTAN CILEXETIL	4	PPARG
TELMISARTAN	4	PPARG
RIMONABANT	4	PPARG
CEFAMANDOLE	4	PPARG
CLOBETASOL PROPIONATE	4	PPARG
ROSIGLITAZONE	4	PPARG
FULVESTRANT	4	PPARG
LIOTHYRONINE	4	PPARG
SULINDAC	4	PPARG
CEFTRIAXONE	4	PPARG
LEVOTHYROXINE	4	PPARG
CEFOTAXIME	4	PPARG
CANNABIDIOL	4	PPARG
TIPRANAVIR	4	PPARG
EFAVIRENZ	4	PPARG
PEMAFIBRATE	4	PPARG
MASOPROCOL	4	PPARG
LASOFOXIFENE	4	PPARG
ELAFIBRANOR	4	PPARG
LUMIRACOXIB	4	PPARG
TROGLITAZONE	4	PPARG
CEFTAZIDIME	4	PPARG
GEMFIBROZIL	4	PPARG
GLYBURIDE	4	PPARG
NINTEDANIB	4	PPARG

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PPARG
B	Phased (≥1) drug, not yet approved	1	FOS
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	AGPAT2
E	Difficult family or no structure, no drug	4	BSCL2, CAV1, CAVIN1, HNRNPUL2-BSCL2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
BSCL2	0	—
CAV1	5	—
AGPAT2	6	—
CAVIN1	0	—
HNRNPUL2-BSCL2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.