Obesity disorder

Summary

Obesity disorder (MONDO:0011122) is a disease caused by HTR2C (GenCC Strong), with 75 cohort genes (1,352 GWAS associations across 202 studies) and 7,775 clinical trials. The dominant Reactome pathway is MECP2 regulates transcription factors (3 cohort genes). Top therapeutic interventions include orlistat, rimonabant, and sibutramine.

At a glance

• Causal gene: HTR2C (GenCC Strong)
• Cohort genes: 75
• GWAS associations: 1,352
• ClinVar variants: 248
• Clinical trials: 7,775

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	obesity disorder
Mondo ID	MONDO:0011122
EFO	EFO:0001073
Orphanet	521399
DOID	DOID:9970
NCIT	C3283
SNOMED CT	414916001
UMLS	C0028754
MedGen	18127
Is cancer (heuristic)	no

Also known as: obesity · obesity disease

Data availability: 248 ClinVar variants · 1,352 GWAS associations (202 studies) · 1 GenCC gene-disease record · 1 HPO phenotype.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › nutritional disorder › overnutrition › obesity disorder

Related subtypes (3): abdominal obesity-metabolic syndrome, hypervitaminosis D, hypervitaminosis A

Subtypes (2): morbid obesity, inherited obesity

Genetics & variants

GWAS landscape

1,352 GWAS associations across 202 studies. Top hits map to 14 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs1421085	6e-291	FTO	T	0.14
rs11642015	5e-162	FTO	C	0.14
rs8043757	5e-110	FTO	T	1.23
rs1558902	2e-81	FTO	A	1.14
rs7185735	1e-79	FTO	G	1.33
rs663129	2e-62	RNU4-17P - MC4R	?	1.13
rs13130484	1e-51	PRDX4P1 - THAP12P9	C	0.06
rs13107325	6e-51	SLC39A8	C	0.11
rs12463617	4e-47	LINC01875 - TMEM18	?	0.9
chr2:622827	5e-46		T	0.07
rs6567160	1e-42	LINC03111 - RNU4-17P	T	0.06
rs688671	1e-40	RNU4-17P - MC4R	?	1.1
rs7186573	2e-40	SGF29	?
rs6711012	3e-40	LINC01875 - TMEM18	C	1.18
chr3:185824004	5e-39		T	0.08
rs574367	9e-38	LINC01741 - SEC16B	?	1.12
chr16:28833299	1e-37		C	0.05
rs538656	2e-36	RNU4-17P - MC4R	T	1.15
rs7204797	2e-34	TMEM219	?
rs10938397	3e-34	PRDX4P1 - THAP12P9	G	1.12
rs1800437	5e-34	GIPR	G	0.06
rs2644112	3e-33	IPO9	?
rs35796073	8e-33	LINC01875 - TMEM18	C	0.07
rs2568952	9e-33	LINC02796	C	0.05
chr3:185805294	3e-32		C	0.07
rs889398	1e-30	CYB5B - NFAT5	?
chr14:79890677	3e-30		C	0.05
rs7132908	6e-30	FAIM2	G	0.04
rs13028310	3e-29	LINC01875 - TMEM18	T	0.07
rs6809651	7e-29	ETV5	G	0.07

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90079764	Backman JD	2021	171,670	194,798	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90083750	Backman JD	2021	171,670	194,798	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90079763	Backman JD	2021	170,856	195,879	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90083749	Backman JD	2021	170,856	195,879	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90081522	Backman JD	2021	104,086	142,553	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90085508	Backman JD	2021	104,086	142,553	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST008976	Jia X	2018	48,286	250,671	Multivariate analysis of genome-wide data to identify potential pleiotropic genes for type 2 diabetes, obesity and coronary artery disease using MetaCCA.
GCST90093121	Park S	2021	17,545	36,283	Interactions between Polygenic Risk Scores, Dietary Pattern, and Menarche Age with the Obesity Risk in a Large Hospital-Based Cohort.
GCST90244581	Kim YS	2022	16,429	34,379	Lifestage Sex-Specific Genetic Effects on Metabolic Disorders in an Adult Population in Korea: The Korean Genome and Epidemiology Study.
GCST90244583	Kim YS	2022	8,616	22,597	Lifestage Sex-Specific Genetic Effects on Metabolic Disorders in an Adult Population in Korea: The Korean Genome and Epidemiology Study.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	2
Tier 2: splice/UTR	1
Tier 3: regulatory	2
Tier 4: intronic/intergenic	45

MAF distribution

Bucket	Variants
common (>=0.05)	50
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	21
unknown	13
intergenic_variant	11
missense_variant	2
regulatory_region_variant	2
3_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs1421085	16	53767042	T>C	0.407	intron_variant	FTO	6e-291	Tier 4: intronic/intergenic
rs11642015	16	53768582	C>G,T	0.328	intron_variant	FTO	5e-162	Tier 4: intronic/intergenic
rs8043757	16	53779538	A>G,T	0.4	intron_variant	FTO	5e-110	Tier 4: intronic/intergenic
rs1558902	16	53769662	T>A	0.41	intron_variant	FTO	2e-81	Tier 4: intronic/intergenic
rs7185735	16	53788739	A>G,T	0.4	intron_variant	FTO	1e-79	Tier 4: intronic/intergenic
rs663129	18	60171168	G>A	0.05	intron_variant	RNU4-17P - MC4R	2e-62	Tier 4: intronic/intergenic
rs13130484	4	45173674	C>A,T	0.428	intergenic_variant	PRDX4P1 - THAP12P9	1e-51	Tier 4: intronic/intergenic
rs13107325	4	102267552	C>A,T	0.083	missense_variant	SLC39A8	6e-51	Tier 1: coding
rs12463617	2	629244	A>C,T	0.05	intergenic_variant	LINC01875 - TMEM18	4e-47	Tier 4: intronic/intergenic
chr2:622827				0.174			5e-46	Tier 4: intronic/intergenic
rs6567160	18	60161902	T>C	0.229	intergenic_variant	LINC03111 - RNU4-17P	1e-42	Tier 4: intronic/intergenic
rs688671	18	60200293	A>G,T	0.05	intergenic_variant	RNU4-17P - MC4R	1e-40	Tier 4: intronic/intergenic
rs7186573	16	28576068	T>C	0.05	intron_variant	SGF29	2e-40	Tier 4: intronic/intergenic
rs6711012	2	624034	G>A,C,T	0.18	intergenic_variant	LINC01875 - TMEM18	3e-40	Tier 4: intronic/intergenic
chr3:185824004				0.151			5e-39	Tier 4: intronic/intergenic
rs574367	1	177904075	G>T	0.05	intron_variant	LINC01741 - SEC16B	9e-38	Tier 4: intronic/intergenic
chr16:28833299				0.395			1e-37	Tier 4: intronic/intergenic
rs538656	18	60183189	G>T	0.24	intergenic_variant	RNU4-17P - MC4R	2e-36	Tier 4: intronic/intergenic
rs7204797	16	29956694	C>T	0.05	intron_variant	TMEM219	2e-34	Tier 4: intronic/intergenic
rs10938397	4	45180510	A>G	0.43	intergenic_variant	PRDX4P1 - THAP12P9	3e-34	Tier 4: intronic/intergenic
rs1800437	19	45678134	G>A,C	0.207	missense_variant	GIPR	5e-34	Tier 1: coding
rs2644112	1	201836978	T>C	0.05	intron_variant	IPO9	3e-33	Tier 4: intronic/intergenic
rs35796073	2	636819	C>A,T	0.156	regulatory_region_variant	LINC01875 - TMEM18	8e-33	Tier 3: regulatory
rs2568952	1	72289422	C>G	0.396	intron_variant	LINC02796	9e-33	Tier 4: intronic/intergenic
chr3:185805294				0.134			3e-32	Tier 4: intronic/intergenic
rs889398	16	69522812	C>T	0.05	regulatory_region_variant	CYB5B - NFAT5	1e-30	Tier 3: regulatory
chr14:79890677				0.207			3e-30	Tier 4: intronic/intergenic
rs7132908	12	49869365	G>A,C	0.387	3_prime_UTR_variant	FAIM2	6e-30	Tier 2: splice/UTR
rs13028310	2	632591	T>A,C,G	0.172	intergenic_variant	LINC01875 - TMEM18	3e-29	Tier 4: intronic/intergenic
rs6809651	3	186096853	G>A	0.141	intron_variant	ETV5	7e-29	Tier 4: intronic/intergenic

ClinVar germline variants

248 retrieved; paginated sample, class counts are floors:

98 uncertain significance, 51 conflicting classifications of pathogenicity, 24 pathogenic, 17 benign/likely benign, 17 likely pathogenic, 14 benign, 13 likely benign, 10 pathogenic/likely pathogenic, 4 risk factor

ClinVar	Variant (HGVS)	Gene	Classification	Review
267861	46;XX;t(2;11)(q11.2;p13)dn		Pathogenic	criteria provided, single submitter
267923	46;XX;t(10;15)(q25.2;q11.2)		Pathogenic	criteria provided, single submitter
268036	46;XX;t(2;10)(q22;22.3)dn		Pathogenic	criteria provided, single submitter
917498	NM_005912.3(MC4R):c.[105C>A;110A>T]		Pathogenic	no assertion criteria provided
1330180	GRCh37/hg19 12p13.33-13.31(chr12:146240-8330229)x3	ANO2	Pathogenic	criteria provided, single submitter
626905	NM_001195305.3(BBIP1):c.109C>T (p.Gln37Ter)	BBIP1	Pathogenic	no assertion criteria provided
523249	GRCh37/hg19 15q11.2(chr15:22765628-23300287)	CYFIP1	Pathogenic	criteria provided, single submitter
39679	NM_015214.3(DDHD2):c.1978G>C (p.Asp660His)	DDHD2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1332907	NM_022552.5(DNMT3A):c.1647C>A (p.Cys549Ter)	DNMT3A	Pathogenic	criteria provided, multiple submitters, no conflicts
1047892	GRCh37/hg19 19p13.3(chr19:3976203-4345430)	EEF2	Pathogenic	criteria provided, single submitter
631526	NM_015047.3(EMC1):c.313C>T (p.Arg105Ter)	EMC1	Pathogenic	criteria provided, single submitter
1179191	NM_006208.3(ENPP1):c.2344C>T (p.Arg782Ter)	ENPP1	Pathogenic	criteria provided, multiple submitters, no conflicts
11985	NM_000170.3(GLDC):c.1545G>C (p.Arg515Ser)	GLDC	Pathogenic	criteria provided, multiple submitters, no conflicts
374113	NM_000516.7(GNAS):c.85C>T (p.Gln29Ter)	GNAS	Pathogenic	criteria provided, multiple submitters, no conflicts
523254	GRCh37/hg19 16p11.2(chr16:29592783-30190568)	INO80E	Pathogenic	criteria provided, single submitter
14420	NM_000238.4(KCNH2):c.1682C>T (p.Ala561Val)	KCNH2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
14318	NM_005912.2(MC4R):c.105C>A (p.Tyr35Ter)	MC4R	Pathogenic	criteria provided, multiple submitters, no conflicts
14329	NM_005912.3(MC4R):c.812G>A (p.Cys271Tyr)	MC4R	Pathogenic	criteria provided, multiple submitters, no conflicts
14331	NM_005912.3(MC4R):c.947T>G (p.Ile316Ser)	MC4R	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
327713	NM_005912.3(MC4R):c.494G>A (p.Arg165Gln)	MC4R	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
36487	NM_005912.3(MC4R):c.835_836dup (p.Phe280fs)	MC4R	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
435828	NM_005912.3(MC4R):c.750_751del (p.Ile251fs)	MC4R	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
435831	NM_005912.3(MC4R):c.181G>A (p.Glu61Lys)	MC4R	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
492863	NM_005912.3(MC4R):c.838T>C (p.Phe280Leu)	MC4R	Pathogenic	no assertion criteria provided
562356	NM_005912.3(MC4R):c.466C>T (p.Gln156Ter)	MC4R	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1330175	GRCh37/hg19 16p12.2(chr16:21751992-22546976)x1	NPIPB4	Pathogenic	criteria provided, single submitter
636300	NM_021969.3(NR0B2):c.227del (p.Phe76fs)	NR0B2	Pathogenic	criteria provided, single submitter
1330178	GRCh37/hg19 8p23.3-23.1(chr8:10501-7214947)x1	OR4F21	Pathogenic	criteria provided, single submitter
206608	NM_002693.3(POLG):c.1270_1271del (p.Leu424fs)	POLG	Pathogenic	criteria provided, multiple submitters, no conflicts
13355	NM_000939.4(POMC):c.-11C>A	POMC	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · Orphanet: 85 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 5

Dual-evidence genes (GWAS + Mendelian — highest-confidence targets)

Gene	HGNC	Evidence routes
BDNF	BDNF	GWAS, Orphanet
SH2B1	SH2B1	GWAS, Orphanet
LEPR	LEPR	GWAS, Orphanet
MC4R	MC4R	GWAS, Orphanet
POMC	POMC	GWAS, Orphanet

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
HTR2C	Strong	Autosomal dominant	obesity disorder

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BDNF	Orphanet:661	Congenital central hypoventilation syndrome
BDNF	Orphanet:893	WAGR syndrome
SH2B1	Orphanet:261197	Proximal 16p11.2 microdeletion syndrome
SH2B1	Orphanet:261222	Distal 16p11.2 microdeletion syndrome
SH2B1	Orphanet:329249	Severe early-onset obesity-insulin resistance syndrome due to SH2B1 deficiency
LEPR	Orphanet:179494	Obesity due to leptin receptor gene deficiency
MC4R	Orphanet:71529	Obesity due to melanocortin 4 receptor deficiency
POMC	Orphanet:71526	Obesity due to pro-opiomelanocortin deficiency
SCN1A	Orphanet:1942	Epilepsy with myoclonic-atonic seizures
SCN1A	Orphanet:2382	Lennox-Gastaut syndrome
SCN1A	Orphanet:293181	Epilepsy of infancy with migrating focal seizures
SCN1A	Orphanet:33069	Dravet syndrome
SCN1A	Orphanet:36387	Genetic epilepsy with febrile seizure plus
SCN1A	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
SCN1A	Orphanet:569	Familial or sporadic hemiplegic migraine
SCNN1A	Orphanet:130	Brugada syndrome
SCNN1A	Orphanet:171876	Generalized pseudohypoaldosteronism type 1
SCNN1A	Orphanet:526	Liddle syndrome
SCNN1A	Orphanet:60033	Idiopathic bronchiectasis
SDCCAG8	Orphanet:110	Bardet-Biedl syndrome
SDCCAG8	Orphanet:3156	Senior-Loken syndrome
SHH	Orphanet:220386	Semilobar holoprosencephaly
SHH	Orphanet:280195	Septopreoptic holoprosencephaly
SHH	Orphanet:280200	Microform holoprosencephaly
SHH	Orphanet:476119	Autosomal dominant preaxial polydactyly-upperback hypertrichosis syndrome
SHH	Orphanet:485275	Acquired schizencephaly
SHH	Orphanet:93321	Isolated radial hemimelia
SHH	Orphanet:93336	Polydactyly of a triphalangeal thumb
SHH	Orphanet:93405	Syndactyly type 4
SHH	Orphanet:93924	Lobar holoprosencephaly
SHH	Orphanet:93925	Alobar holoprosencephaly
SHH	Orphanet:93926	Midline interhemispheric variant of holoprosencephaly
SHH	Orphanet:988	Tibial hemimelia-polysyndactyly-triphalangeal thumb syndrome
SHH	Orphanet:98938	Colobomatous microphthalmia
SIM1	Orphanet:171829	6q16 microdeletion syndrome
SIM1	Orphanet:369873	Obesity due to SIM1 deficiency
SIM1	Orphanet:398079	SIM1-related Prader-Willi-like syndrome
SLC32A1	Orphanet:1934	Early infantile developmental and epileptic encephalopathy
SLC32A1	Orphanet:36387	Genetic epilepsy with febrile seizure plus
SMARCA4	Orphanet:1465	Coffin-Siris syndrome
SMARCA4	Orphanet:231108	Rhabdoid tumor predisposition syndrome
SMARCA4	Orphanet:370396	Small cell carcinoma of the ovary
SMARCA4	Orphanet:466962	SMARCA4-deficient sarcoma of thorax
ARID1A	Orphanet:1465	Coffin-Siris syndrome
SOS1	Orphanet:2024	Hereditary gingival fibromatosis
SOS1	Orphanet:648	Noonan syndrome
SOX11	Orphanet:1465	Coffin-Siris syndrome
SREBF1	Orphanet:388	Hirschsprung disease
TBCE	Orphanet:2323	Sanjad-Sakati syndrome
TBCE	Orphanet:496756	Early-onset progressive encephalopathy-spastic ataxia-distal spinal muscular atrophy syndrome

Cohort genes → proteins

75 cohort genes, 73 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	39
gwas_and_clinvar	5
multi_evidence	31

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BDNF	HGNC:1033	ENSG00000176697	P23560	Neurotrophic factor BDNF precursor form	gwas,clinvar
SH2B1	HGNC:30417	ENSG00000178188	Q9NRF2	SH2B adapter protein 1	gwas,clinvar
LEPR	HGNC:6554	ENSG00000116678	P48357	Leptin receptor	gwas,clinvar
MC4R	HGNC:6932	ENSG00000166603	P32245	Melanocortin receptor 4	gwas,clinvar
POMC	HGNC:9201	ENSG00000115138	P01189	Pro-opiomelanocortin	gwas,clinvar
HTR2C	HGNC:5295	ENSG00000147246	P28335	5-hydroxytryptamine receptor 2C	gencc
RGS6	HGNC:10002	ENSG00000182732	P49758	Regulator of G-protein signaling 6	gwas
RPL27A	HGNC:10329	ENSG00000166441	P46776	Large ribosomal subunit protein uL15	gwas
SCN1A	HGNC:10585	ENSG00000144285	P35498	Sodium channel protein type 1 subunit alpha	clinvar
SCNN1A	HGNC:10599	ENSG00000111319	P37088	Epithelial sodium channel subunit alpha	gwas
SDCCAG8	HGNC:10671	ENSG00000054282	Q86SQ7	Serologically defined colon cancer antigen 8	gwas
SHH	HGNC:10848	ENSG00000164690	Q15465	Sonic hedgehog protein	clinvar
SIM1	HGNC:10882	ENSG00000112246	P81133	Single-minded homolog 1	clinvar
SLC32A1	HGNC:11018	ENSG00000101438	Q9H598	Vesicular inhibitory amino acid transporter	clinvar
SLC8A1	HGNC:11068	ENSG00000183023	P32418	Sodium/calcium exchanger 1	gwas
SMARCA4	HGNC:11100	ENSG00000127616	P51532	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4	clinvar
ARID1A	HGNC:11110	ENSG00000117713	O14497	AT-rich interactive domain-containing protein 1A	clinvar
SOS1	HGNC:11187	ENSG00000115904	Q07889	Son of sevenless homolog 1	clinvar
SOX11	HGNC:11191	ENSG00000176887	P35716	Transcription factor SOX-11	gwas
SPRY2	HGNC:11270	ENSG00000136158	O43597	Protein sprouty homolog 2	gwas
SREBF1	HGNC:11289	ENSG00000072310	P36956	Sterol regulatory element-binding protein 1	clinvar
TBCE	HGNC:11582	ENSG00000284770	Q15813	Tubulin-specific chaperone E	gwas
TBX3	HGNC:11602	ENSG00000135111	O15119	T-box transcription factor TBX3	clinvar
TCF4	HGNC:11634	ENSG00000196628	P15884	Transcription factor 4	gwas
TFAP2B	HGNC:11743	ENSG00000008196	Q92481	Transcription factor AP-2-beta	gwas
ANO2	HGNC:1183	ENSG00000047617	Q9NQ90	Anoctamin-2	clinvar
TNKS	HGNC:11941	ENSG00000173273	O95271	Poly [ADP-ribose] polymerase tankyrase-1	gwas
UBE2E3	HGNC:12479	ENSG00000170035	Q969T4	Ubiquitin-conjugating enzyme E2 E3	gwas
UCP3	HGNC:12519	ENSG00000175564	P55916	Putative mitochondrial transporter UCP3	clinvar
WWOX	HGNC:12799	ENSG00000186153	Q9NZC7	WW domain-containing oxidoreductase	gwas
ZNF248	HGNC:13041	ENSG00000198105	Q8NDW4	Zinc finger protein 248	gwas
SCAPER	HGNC:13081	ENSG00000140386	Q9BY12	S phase cyclin A-associated protein in the endoplasmic reticulum	clinvar
GPRC5B	HGNC:13308	ENSG00000167191	Q9NZH0	G-protein coupled receptor family C group 5 member B	gwas
KIF4A	HGNC:13339	ENSG00000090889	O95239	Chromosome-associated kinesin KIF4A	clinvar
FBXO11	HGNC:13590	ENSG00000138081	Q86XK2	F-box only protein 11	clinvar
CABP5	HGNC:13714	ENSG00000105507	Q9NP86	Calcium-binding protein 5	gwas
CYFIP1	HGNC:13759	ENSG00000273749	Q7L576	Cytoplasmic FMR1-interacting protein 1	clinvar
RTN4	HGNC:14085	ENSG00000115310	Q9NQC3	Reticulon-4	gwas
CMYA5	HGNC:14305	ENSG00000164309	Q8N3K9	Cardiomyopathy-associated protein 5	gwas
MRPS22	HGNC:14508	ENSG00000175110	P82650	Small ribosomal subunit protein mS22	gwas
VPS45	HGNC:14579	ENSG00000136631	Q9NRW7	Vacuolar protein sorting-associated protein 45	gwas
CAMK1G	HGNC:14585	ENSG00000008118	Q96NX5	Calcium/calmodulin-dependent protein kinase type 1G	gwas
DEAF1	HGNC:14677	ENSG00000177030	O75398	Deformed epidermal autoregulatory factor 1 homolog	clinvar
OR10R1P	HGNC:14813	ENSG00000227445		olfactory receptor family 10 subfamily R member 1 pseudogene	gwas
OR6Y1	HGNC:14823	ENSG00000197532	Q8NGX8	Olfactory receptor 6Y1	gwas
MUC15	HGNC:14956	ENSG00000169550	Q8N387	Mucin-15	gwas
OR6P1	HGNC:15036	ENSG00000186440	Q8NGX9	Olfactory receptor 6P1	gwas
CAST	HGNC:1515	ENSG00000153113	P20810	Calpastatin	clinvar
TDH	HGNC:15547	ENSG00000154316	Q8IZJ6	Inactive L-threonine 3-dehydrogenase, mitochondrial	gwas
NAV3	HGNC:15998	ENSG00000067798	Q8IVL0	Neuron navigator 3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BDNF	Neurotrophic factor BDNF precursor form	Important signaling molecule that activates signaling cascades downstream of NTRK2.
SH2B1	SH2B adapter protein 1	Adapter protein for several members of the tyrosine kinase receptor family.
LEPR	Leptin receptor	Receptor for hormone LEP/leptin.
MC4R	Melanocortin receptor 4	G protein-coupled receptor that binds melanocyte-stimulating hormones (alpha- and beta-MSH) and corticotropin/ACTH, which are peptide products of the POMC precursor.
POMC	Pro-opiomelanocortin	Precursor protein of pituitary hormones that are involved in diverse physiological processes, including the regulation of energy balance, stress response, immune function and skin pigmentation.
HTR2C	5-hydroxytryptamine receptor 2C	G-protein coupled receptor for 5-hydroxytryptamine (serotonin).
RGS6	Regulator of G-protein signaling 6	Regulates G protein-coupled receptor signaling cascades.
RPL27A	Large ribosomal subunit protein uL15	Component of the large ribosomal subunit.
SCN1A	Sodium channel protein type 1 subunit alpha	Pore-forming subunit of Nav1.1, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes.
SCNN1A	Epithelial sodium channel subunit alpha	This is one of the three pore-forming subunits of the heterotrimeric epithelial sodium channel (ENaC), a critical regulator of sodium balance and fluid homeostasis.
SDCCAG8	Serologically defined colon cancer antigen 8	Plays a role in the establishment of cell polarity and epithelial lumen formation.
SHH	Sonic hedgehog protein	The C-terminal part of the sonic hedgehog protein precursor displays an autoproteolysis and a cholesterol transferase activity.
SIM1	Single-minded homolog 1	Transcriptional factor that may have pleiotropic effects during embryogenesis and in the adult.
SLC32A1	Vesicular inhibitory amino acid transporter	Antiporter that exchanges vesicular protons for cytosolic 4-aminobutanoate or to a lesser extend glycine, thus allowing their secretion from nerve terminals.
SLC8A1	Sodium/calcium exchanger 1	Mediates the exchange of one Ca(2+) ion against three to four Na(+) ions across the cell membrane, and thereby contributes to the regulation of cytoplasmic Ca(2+) levels and Ca(2+)-dependent cellular processes.
SMARCA4	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4	ATPase involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
ARID1A	AT-rich interactive domain-containing protein 1A	Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
SOS1	Son of sevenless homolog 1	Promotes the exchange of Ras-bound GDP by GTP.
SOX11	Transcription factor SOX-11	Transcription factor that acts as a transcriptional activator.
SPRY2	Protein sprouty homolog 2	Antagonist of fibroblast growth factor (FGF) pathways via inhibition of FGF-mediated phosphorylation of ERK1/2.
SREBF1	Sterol regulatory element-binding protein 1	Precursor of the transcription factor form (Processed sterol regulatory element-binding protein 1), which is embedded in the endoplasmic reticulum membrane.
TBCE	Tubulin-specific chaperone E	Tubulin-folding protein; involved in the second step of the tubulin folding pathway and in the regulation of tubulin heterodimer dissociation.
TBX3	T-box transcription factor TBX3	Transcriptional repressor involved in developmental processes.
TCF4	Transcription factor 4	Transcription factor that binds to the immunoglobulin enhancer Mu-E5/KE5-motif.
TFAP2B	Transcription factor AP-2-beta	Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes.
ANO2	Anoctamin-2	Calcium-activated chloride channel (CaCC) which may play a role in olfactory signal transduction.
TNKS	Poly [ADP-ribose] polymerase tankyrase-1	Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking.
UBE2E3	Ubiquitin-conjugating enzyme E2 E3	Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins.
UCP3	Putative mitochondrial transporter UCP3	Putative transmembrane transporter that plays a role in mitochondrial metabolism via an as yet unclear mechanism.
WWOX	WW domain-containing oxidoreductase	Putative oxidoreductase.
ZNF248	Zinc finger protein 248	May be involved in transcriptional regulation.
SCAPER	S phase cyclin A-associated protein in the endoplasmic reticulum	CCNA2/CDK2 regulatory protein that transiently maintains CCNA2 in the cytoplasm.
GPRC5B	G-protein coupled receptor family C group 5 member B	G-protein coupled receptor involved in the regulation of cell volume.
KIF4A	Chromosome-associated kinesin KIF4A	Iron-sulfur (Fe-S) cluster binding motor protein that has a role in chromosome segregation during mitosis.
FBXO11	F-box only protein 11	Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as DTL/CDT2, BCL6, SNAI1 and PRDM1/BLI…
CABP5	Calcium-binding protein 5	Inhibits calcium-dependent inactivation of L-type calcium channel and shifts voltage dependence of activation to more depolarized membrane potentials.
CYFIP1	Cytoplasmic FMR1-interacting protein 1	Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression.
RTN4	Reticulon-4	Required to induce the formation and stabilization of endoplasmic reticulum (ER) tubules.
CMYA5	Cardiomyopathy-associated protein 5	May serve as an anchoring protein that mediates the subcellular compartmentation of protein kinase A (PKA) via binding to PRKAR2A.
VPS45	Vacuolar protein sorting-associated protein 45	May play a role in vesicle-mediated protein trafficking from the Golgi stack through the trans-Golgi network.
CAMK1G	Calcium/calmodulin-dependent protein kinase type 1G	Calcium/calmodulin-dependent protein kinase belonging to a proposed calcium-triggered signaling cascade.
DEAF1	Deformed epidermal autoregulatory factor 1 homolog	Transcription factor that binds to sequence with multiple copies of 5’-TTC[CG]G-3’ present in its own promoter and that of the HNRPA2B1 gene.
OR6Y1	Olfactory receptor 6Y1	Odorant receptor.
MUC15	Mucin-15	May play a role in the cell adhesion to the extracellular matrix.
OR6P1	Olfactory receptor 6P1	Odorant receptor.
CAST	Calpastatin	Specific inhibition of calpain (calcium-dependent cysteine protease).
NAV3	Neuron navigator 3	Is involved in microtubule cytoskeleton organization and plays a role in cell migration.
MACROD2	ADP-ribose glycohydrolase MACROD2	Removes ADP-ribose from aspartate and glutamate residues in proteins bearing a single ADP-ribose moiety.
SOX6	Transcription factor SOX-6	Transcription factor that plays a key role in several developmental processes, including neurogenesis, chondrocytes differentiation and cartilage formation.
OLFM4	Olfactomedin-4	May promote proliferation of pancreatic cancer cells by favoring the transition from the S to G2/M phase.

Protein-family classification

Druggable: 19 · Difficult: 21 · Unknown: 35 · Druggable fraction: 0.25

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
Transcription factor	16	1.8×	0.147
GPCR	6	1.9×	0.419
Ion channel	1	1.5×	0.738
Kinase	4	1.5×	0.738
Antibody/Immunoglobulin	3	1.2×	0.738
Scaffold/PPI	5	1.1×	0.738
Transporter	1	1.0×	0.799
Other/Unknown	35	0.8×	0.956
Enzyme (other)	4	0.6×	0.956

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BDNF	Other/Unknown	no		Nerve_growth_factor-rel, Nerve_growth_factor_CS, Nerve_growth_factor-like
SH2B1	Scaffold/PPI	no		SH2, PH_domain, PH-like_dom_sf
LEPR	Antibody/Immunoglobulin	yes		Hematopoietin_rcpt_Gp130_CS, Hempt_rcpt_S_F1_CS, FN3_dom
MC4R	GPCR	yes		Mcort_rcpt_4, GPCR_Rhodpsn, Melcrt_ACTH_rcpt
POMC	Other/Unknown	no		PMOC, Mcrtin_ACTH_cent, Opioid_neuropept
HTR2C	GPCR	yes		GPCR_Rhodpsn, 5HT2C_rcpt, 5HT_rcpt
RGS6	Other/Unknown	no		DEP_dom, G-protein_gamma-like_dom, RGS
RPL27A	Other/Unknown	no		Ribosomal_uL15_CS, Ribosomal_uL15/eL18, Rbsml_uL15_N
SCN1A	Ion channel	yes		Na_channel_asu, Ion_trans_dom, Na_channel_a1su
SCNN1A	Other/Unknown	no		ENaC, ENaC_chordates, ENaC_CS
SDCCAG8	Other/Unknown	no		SDCCAG8
SHH	Other/Unknown	no		Hedgehog_signalling_dom, Hedgehog, Hedgehog_Hint
SIM1	Transcription factor	no		PAS, PAC, SIM_C
SLC32A1	Other/Unknown	no		AA_transpt_TM
SLC8A1	Other/Unknown	no		DnaJ_domain, NaCa_exhngr1, Calx_beta
SMARCA4	Other/Unknown	no		SNF2_N, Bromodomain, Helicase_C-like
ARID1A	Other/Unknown	no		ARID_dom, ARM-like, ARM-type_fold
SOS1	Scaffold/PPI	no		DH_dom, Ras-like_Gua-exchang_fac_N, PH_domain
SOX11	Transcription factor	no		HMG_box_dom, SOX-12/11/4, HMG_box_dom_sf
SPRY2	Other/Unknown	no		Sprouty, Sprouty_domain
SREBF1	Transcription factor	no		bHLH_dom, HLH_DNA-bd_sf
TBCE	Other/Unknown	no		Ubiquitin-like_dom, CAP-Gly_domain, Ubiquitin-like_domsf
TBX3	Transcription factor	no		TF_T-box, p53-like_TF_DNA-bd_sf, TF_T-box_CS
TCF4	Transcription factor	no	7.6.2.3	bHLH_dom, HLH_DNA-bd_sf, NeuroDiff_E-box_TFs
TFAP2B	Transcription factor	no		TF_AP2, TF_AP2_beta, TF_AP2_C
ANO2	Other/Unknown	no		Anoctamin, Anoct_dimer, Anoctamin_TM
TNKS	Scaffold/PPI	no	2.4.2.30	SAM, Ankyrin_rpt, Poly(ADP-ribose)pol_cat_dom
UBE2E3	Enzyme (other)	yes	2.3.2.23	UBC, UBQ-conjugating_enzyme/RWD, UBQ-conjugating_AS
UCP3	Transporter	yes		MCP, MCP_transmembrane, MCP_dom_sf
WWOX	Scaffold/PPI	no		WW_dom, SDR_fam, WW_dom_sf
ZNF248	Transcription factor	no		KRAB, Znf_C2H2_type, KRAB_dom_sf
SCAPER	Transcription factor	no		Matrin/U1-like-C_Znf_C2H2, Znf_C2H2_type, SCAPER_N
GPRC5B	GPCR	yes		GPCR_3_C, RA-inducible_GPCR3
KIF4A	Other/Unknown	no		Kinesin_motor_dom, Kinesin_motor_CS, P-loop_NTPase
FBXO11	Transcription factor	no		F-box_dom, Znf_UBR, PbH1
CABP5	Other/Unknown	no		EF_hand_dom, EF-hand-dom_pair, EF_Hand_1_Ca_BS
CYFIP1	Other/Unknown	no		Cytoplasmic_FMR1-int, CYRIA/CYRIB_Rac1-bd
RTN4	Other/Unknown	no		Reticulon, RTN1-4
CMYA5	Antibody/Immunoglobulin	yes		B30.2/SPRY, SPRY_dom, FN3_dom
MRPS22	Other/Unknown	no		Ribosomal_mS22
VPS45	Other/Unknown	no		Sec1-like, Sec1-like_dom2, Sec1-like_sf
CAMK1G	Kinase	yes	2.7.11.17	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
DEAF1	Transcription factor	no		SAND_dom, Znf_MYND, SAND-like_dom_sf
OR10R1P	Other/Unknown	no
OR6Y1	GPCR	yes		GPCR_Rhodpsn, Olfact_rcpt, GPCR_Rhodpsn_7TM
MUC15	Other/Unknown	no		Mucin-15
OR6P1	GPCR	yes		GPCR_Rhodpsn, Olfact_rcpt, GPCR_Rhodpsn_7TM
CAST	Other/Unknown	no		Prot_inh_calpain, Calpastatin
TDH	Other/Unknown	no		Epimerase_deHydtase, NAD(P)-bd_dom_sf, NAD(P)_epim/dehydratase
NAV3	Other/Unknown	no		CH_dom, AAA+_ATPase, ATPase_AAA_core

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	3
moderate (6-20)	0
broad (>20)	72
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	12
middle temporal gyrus	9
Brodmann (1909) area 23	8
ventricular zone	8
ganglionic eminence	7
calcaneal tendon	6
endothelial cell	6
sural nerve	5
colonic epithelium	5
male germ line stem cell (sensu Vertebrata) in testis	5
oocyte	4
right hemisphere of cerebellum	4
buccal mucosa cell	4
cerebellar hemisphere	3
right uterine tube	3
adenohypophysis	3
bone marrow cell	3
epithelial cell of pancreas	3
tendon of biceps brachii	3
right adrenal gland	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BDNF	189	ubiquitous	yes	saphenous vein, pons, oocyte
SH2B1	253	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
LEPR	272	broad	marker	trabecular bone tissue, choroid plexus epithelium, trigeminal ganglion
MC4R	69	broad	yes	pancreatic ductal cell, right uterine tube, prefrontal cortex
POMC	161	broad	marker	adenohypophysis, pituitary gland, right testis
HTR2C	79	tissue_specific	marker	choroid plexus epithelium, lateral globus pallidus, superior vestibular nucleus
RGS6	185	broad	marker	cortical plate, sural nerve, middle temporal gyrus
RPL27A	188	ubiquitous	marker	bone marrow cell, adenohypophysis, ganglionic eminence
SCN1A	154	tissue_specific	marker	Brodmann (1909) area 23, lateral nuclear group of thalamus, primary visual cortex
SCNN1A	283	broad	marker	nasal cavity epithelium, metanephros cortex, right uterine tube
SDCCAG8	134	ubiquitous	marker	corpus callosum, calcaneal tendon, thyroid gland
SHH	131	broad	marker	buccal mucosa cell, right lobe of liver, epithelial cell of pancreas
SIM1	76	broad	yes	renal medulla, skeletal muscle tissue of biceps brachii, biceps brachii
SLC32A1	69	broad	marker	nucleus accumbens, putamen, prefrontal cortex
SLC8A1	249	ubiquitous	marker	heart right ventricle, adrenal tissue, endothelial cell
SMARCA4	295	ubiquitous	marker	ganglionic eminence, cortical plate, cervix squamous epithelium
ARID1A	286	ubiquitous	marker	bone marrow cell, ventricular zone, embryo
SOS1	289	ubiquitous	marker	colonic epithelium, jejunal mucosa, tendon of biceps brachii
SOX11	93	broad	marker	ganglionic eminence, cortical plate, embryo
SPRY2	281	ubiquitous	marker	cartilage tissue, tibial nerve, right hemisphere of cerebellum
SREBF1	172	ubiquitous	marker	left adrenal gland, right adrenal gland, left adrenal gland cortex
TBCE	134	ubiquitous	yes	ventricular zone, hindlimb stylopod muscle, cortical plate
TBX3	243	ubiquitous	marker	right adrenal gland cortex, right adrenal gland, adrenal cortex
TCF4	292	ubiquitous	marker	endothelial cell, skin of hip, pericardium
TFAP2B	128	broad	marker	corpus epididymis, cauda epididymis, oocyte
ANO2	165	tissue_specific	marker	sural nerve, left testis, calcaneal tendon
TNKS	295	ubiquitous	yes	middle temporal gyrus, medial globus pallidus, Brodmann (1909) area 23
UBE2E3	134	ubiquitous	marker	ganglionic eminence, cortical plate, stromal cell of endometrium
UCP3	224	tissue_specific	marker	gastrocnemius, hindlimb stylopod muscle, muscle of leg
WWOX	286	ubiquitous	marker	parotid gland, cervix squamous epithelium, cranial nerve II

Protein interactions among cohort

Intra-cohort edges: 33.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SMARCA4	8,138
WWOX	5,892
BDNF	5,587
SHH	4,953
RPL27A	4,738
SETD2	4,668
SREBF1	4,089
POMC	3,655
SOS1	3,625
ARID1A	3,476

Intra-cohort edges

A	B	Sources
ALPK1	CABP5	string_interaction
ARID1A	CDH18	string_interaction
ARID1A	SMARCA4	biogrid_interaction, intact, string_interaction
ARID1A	SOX11	string_interaction
CABP5	TCF4	biogrid_interaction, intact
CDH10	CDH18	string_interaction
CHAMP1	POGZ	biogrid_interaction, string_interaction
FANCL	GPRC5B	string_interaction
GHRL	MC4R	string_interaction
GHRL	POMC	string_interaction
GHRL	UCP3	string_interaction
GPRC5B	HTR2C	intact
GPRC5B	NEGR1	string_interaction
GPRC5B	TNNI3K	string_interaction
HTR2C	POMC	string_interaction
HTR2C	RTN4	intact
LEPR	MC4R	string_interaction
LEPR	POMC	string_interaction
LEPR	SH2B1	string_interaction
LYPLAL1	TFAP2B	string_interaction
MACROD2	RBFOX1	string_interaction
MACROD2	WWOX	string_interaction
MC4R	NEGR1	string_interaction
MC4R	POMC	string_interaction
MC4R	SH2B1	string_interaction
MC4R	SIM1	string_interaction
MC4R	TFAP2B	string_interaction
NEGR1	SH2B1	string_interaction
NEGR1	TFAP2B	string_interaction
POMC	SIM1	string_interaction
SIM1	SLC32A1	string_interaction
SMARCA4	SOX11	string_interaction
TFAP2B	TNNI3K	string_interaction

Structural data

PDB: 50 · AlphaFold-only: 23 · No structure: 2

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RPL27A	P46776	193
SOS1	Q07889	91
MRPS22	P82650	77
SETD2	Q9BYW2	43
TNKS	O95271	42
SMARCA4	P51532	31
SHH	Q15465	20
POMC	P01189	13
PRMT6	Q96LA8	13
MC4R	P32245	12
LEPR	P48357	9
KSR2	Q6VAB6	9
FARS2	O95363	9
HTR2C	P28335	8
FANCL	Q9NW38	8
ARID1A	O14497	7
TBCE	Q15813	6
SLC8A1	P32418	5
SPRY2	O43597	5
TCF4	P15884	5
CYFIP1	Q7L576	5
TNNI3K	Q59H18	5
SOX11	P35716	4
MACROD2	A1Z1Q3	4
GHRL	Q9UBU3	4
RBFOX1	Q9NWB1	4
CHAMP1	Q96JM3	4
SCNN1A	P37088	3
DEAF1	O75398	3
KAT6B	Q8WYB5	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
VPS45	Q9NRW7	90.65
OR4F21	O95013	90.19
OR6Y1	Q8NGX8	86.47
OR6P1	Q8NGX9	85.34
OLFM4	Q6UX06	83.34
CDKAL1	Q5VV42	82.72
HS6ST3	Q8IZP7	81.20
CABP5	Q9NP86	79.89
SLC32A1	Q9H598	78.69
SDCCAG8	Q86SQ7	78.67
CDH10	Q9Y6N8	78.29
CDH18	Q13634	77.57
TDH	Q8IZJ6	77.16
ANO2	Q9NQ90	74.81
GPRC5B	Q9NZH0	74.39
UCP3	P55916	62.65
SIM1	P81133	60.70
CAST	P20810	59.67
SOX6	P35712	56.48
ZNF248	Q8NDW4	55.52
MUC15	Q8N387	52.21
NAV3	Q8IVL0	48.21
CMYA5	Q8N3K9

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 638. Enrichment computed across 181 evidence-associated genes (126 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 126 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
MECP2 regulates transcription factors	3	54.4×	0.008	RBFOX1, MECP2, PPARG
Signal Transduction	28	2.3×	0.009	BDNF, MC4R, SHH, SMARCA4, SOS1, SPRY2, TCF4, RTN4 (+20 more)
Signaling by NTRKs	6	8.6×	0.014	BDNF, SOS1, KIDINS220, IRS1, MAP2K1, MAP2K5
BDNF activates NTRK2 (TRKB) signaling	2	90.6×	0.019	BDNF, NTRK2
Activated NTRK2 signals through RAS	3	27.2×	0.019	BDNF, SOS1, NTRK2
Signaling by Leptin	3	24.7×	0.019	SH2B1, LEPR, IRS1
Activated NTRK2 signals through FRS2 and FRS3	3	22.7×	0.019	BDNF, SOS1, NTRK2
Anti-inflammatory response favouring Leishmania parasite infection	4	12.5×	0.019	ADCY3, ADCY9, ITPR3, MYH9
Leishmania parasite growth and survival	4	12.5×	0.019	ADCY3, ADCY9, ITPR3, MYH9
G alpha (s) signalling events	8	4.7×	0.019	MC4R, POMC, ADCY3, ADCY9, ADRB3, GIPR, GNAS, MC3R
Signaling by GPCR	11	3.5×	0.019	MC4R, SHH, SOS1, ADCY3, ADCY9, ADRB3, HTR2C, ITPR3 (+3 more)
Diseases of signal transduction by growth factor receptors and second messengers	9	4.1×	0.020	BDNF, SHH, SOS1, KSR2, AMER1, IRS1, LRRFIP1, MAP2K1 (+1 more)
Signaling by NTRK1 (TRKA)	5	7.8×	0.021	SOS1, KIDINS220, IRS1, MAP2K1, MAP2K5
Loss of MECP2 binding ability to 5mC-DNA	2	45.3×	0.028	BDNF, MECP2
Activated NTRK2 signals through PLCG1	2	45.3×	0.028	BDNF, NTRK2
GPCR downstream signalling	10	3.5×	0.028	MC4R, SOS1, ADCY3, ADCY9, ADRB3, HTR2C, ITPR3, MC3R (+2 more)
PKA activation in glucagon signalling	3	16.0×	0.029	ADCY3, ADCY9, GNAS
MITF-M-regulated melanocyte development	6	5.4×	0.029	MC4R, SMARCA4, ARID1A, TBX3, MC3R, ASAH1
Signalling to ERKs	3	14.3×	0.038	SOS1, KIDINS220, MAP2K1
Formation of lateral plate mesoderm	2	36.2×	0.038	SHH, FOXF1
Opioid Signalling	4	8.4×	0.038	POMC, ADCY3, ADCY9, ITPR3
Activated NTRK2 signals through FYN	2	30.2×	0.045	BDNF, NTRK2
NTRK2 activates RAC1	2	30.2×	0.045	BDNF, NTRK2
Activated NTRK2 signals through CDK5	2	30.2×	0.045	BDNF, NTRK2
RMTs methylate histone arginines	5	5.8×	0.045	SMARCA4, ARID1A, PRMT6, PRMT7, DNMT3A
G alpha (z) signalling events	4	7.4×	0.050	ADCY3, ADCY9, GNAS, PRKCH
Sensory Perception	6	4.5×	0.050	SCNN1A, ANO2, ADCY3, ITPR3, KCNMA1, MYH9
Growth hormone receptor signaling	3	11.3×	0.051	SH2B1, IRS1, PRL
Signaling by NTRK2 (TRKB)	2	25.9×	0.052	BDNF, SOS1
Activated NTRK2 signals through PI3K	2	25.9×	0.052	BDNF, NTRK2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 165 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
feeding behavior	5	16.5×	0.018	MC4R, NEGR1, HTR2C, NTRK2, PYY
glial cell proliferation	4	21.5×	0.023	LEPR, SOX11, EEF2, MECP2
negative regulation of locomotion	2	102.1×	0.032	GHRL, CARTPT
regulation of feeding behavior	3	34.0×	0.032	LEPR, MC4R, MC3R
regulation of appetite	3	30.6×	0.032	POMC, HTR2C, PTER
regulation of heart rate by chemical signal	2	68.1×	0.035	SREBF1, CARTPT
positive regulation of growth rate	2	68.1×	0.035	GHRL, RFTN1
response to melanocyte-stimulating hormone	2	68.1×	0.035	MC4R, POMC
cAMP biosynthetic process	3	25.5×	0.035	ADCY3, ADCY9, CARTPT
adenylate cyclase-activating adrenergic receptor signaling pathway	3	21.9×	0.035	ADCY9, ADRB3, GNAS
negative regulation of insulin secretion	4	12.0×	0.035	SREBF1, GHRL, INHBB, IRS1
insulin-like growth factor receptor signaling pathway	4	12.0×	0.035	SOS1, IRS1, MAP2K1, MAP2K5
response to nutrient	5	9.0×	0.035	SREBF1, UCP3, GIPR, MAF, PPARG
social behavior	5	8.2×	0.035	NEGR1, RPTOR, MECP2, NRXN1, NRXN3
negative regulation of transcription by RNA polymerase II	22	2.4×	0.035	SHH, SMARCA4, SOX11, SREBF1, TBX3, TFAP2B, DEAF1, PHF6 (+14 more)
positive regulation of heart growth	2	51.1×	0.043	PROX1, BASP1
neuron cell-cell adhesion	3	18.0×	0.043	NCAM2, NRXN1, NRXN3
circadian rhythm	5	7.4×	0.043	SREBF1, MTNR1A, NR0B2, NTRK2, PROX1
positive regulation of synapse assembly	5	7.4×	0.043	BDNF, GHRL, LINGO2, NRXN1, NTRK2
positive regulation of cold-induced thermogenesis	6	6.0×	0.043	LEPR, SMARCA4, GHRL, KSR2, ADRB3, GNAS
embryonic digestive tract morphogenesis	3	17.0×	0.049	SHH, SOX11, FOXF1
brain-derived neurotrophic factor receptor signaling pathway	2	40.9×	0.056	BDNF, NTRK2
ductus arteriosus closure	2	40.9×	0.056	TFAP2B, FOXF1
cellular response to glucagon stimulus	3	15.3×	0.056	ADCY3, ADCY9, GNAS
positive regulation of DNA-templated transcription	15	2.5×	0.056	SHH, SMARCA4, ARID1A, TCF4, TFAP2B, DEAF1, KAT6B, INO80D (+7 more)
nervous system development	11	3.1×	0.058	BDNF, SIM1, SMARCA4, ARID1A, SOX11, TCF4, TFAP2B, NAV3 (+3 more)
negative regulation of eating behavior	2	34.0×	0.072	MC4R, CARTPT
vascular endothelial cell response to laminar fluid shear stress	3	13.3×	0.072	ADCY3, ADCY9, GNAS
generation of precursor metabolites and energy	4	8.3×	0.072	POMC, ADRB3, ENPP1, GIPR
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	4	8.2×	0.072	MC4R, ADRB3, GIPR, GNAT2

Therapeutics

Drugs indicated for this disease

17 approved, 39 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Choriogonadotropin Alfa	Approved (phase 4)
Clobenzorex	Approved (phase 4)
Dexfenfluramine	Approved (phase 4)
Diethylpropion	Approved (phase 4)
Ephedrine	Approved (phase 4)
Fenfluramine	Approved (phase 4)
Liraglutide	Approved (phase 4)
Lorcaserin	Approved (phase 4)
Mazindol	Approved (phase 4)
Mefenorex	Approved (phase 4)
Orlistat	Approved (phase 4)
Phentermine	Approved (phase 4)
Rimonabant	Approved (phase 4)
Semaglutide	Approved (phase 4)
Setmelanotide	Approved (phase 4)
Sibutramine	Approved (phase 4)
Tirzepatide	Approved (phase 4)
Acetaminophen	Phase 3 (in late-stage trials)
Allopurinol	Phase 3 (in late-stage trials)
Armodafinil	Phase 3 (in late-stage trials)
Beloranib	Phase 3 (in late-stage trials)
Bupropion	Phase 3 (in late-stage trials)
Caffeine	Phase 3 (in late-stage trials)
Cagrilintide	Phase 3 (in late-stage trials)
Calcium	Phase 3 (in late-stage trials)
Cholecalciferol	Phase 3 (in late-stage trials)
Dexmedetomidine	Phase 3 (in late-stage trials)
Diazoxide	Phase 3 (in late-stage trials)
Efpeglenatide	Phase 3 (in late-stage trials)
Enoxaparin Sodium	Phase 3 (in late-stage trials)
Ergocalciferol	Phase 3 (in late-stage trials)
Estradiol	Phase 3 (in late-stage trials)
Exenatide	Phase 3 (in late-stage trials)
Fentanyl	Phase 3 (in late-stage trials)
Fish Oil	Phase 3 (in late-stage trials)
Fospropofol	Phase 3 (in late-stage trials)
Icosapent	Phase 3 (in late-stage trials)
Lamotrigine	Phase 3 (in late-stage trials)
Lidocaine	Phase 3 (in late-stage trials)
MK-0557	Phase 3 (in late-stage trials)
Mazdutide	Phase 3 (in late-stage trials)
Metformin	Phase 3 (in late-stage trials)
Metreleptin	Phase 3 (in late-stage trials)
Milk Thistle	Phase 3 (in late-stage trials)
Misoprostol	Phase 3 (in late-stage trials)
Morphine	Phase 3 (in late-stage trials)
Naltrexone	Phase 3 (in late-stage trials)
Otenabant	Phase 3 (in late-stage trials)
Probenecid	Phase 3 (in late-stage trials)
Propofol	Phase 3 (in late-stage trials)
Retatrutide	Phase 3 (in late-stage trials)
Rosuvastatin	Phase 3 (in late-stage trials)
Sodium Chloride	Phase 3 (in late-stage trials)
Somatropin	Phase 3 (in late-stage trials)
Taranabant	Phase 3 (in late-stage trials)
Topiramate	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Alcohol, Apitegromab, Avexitide, Betahistine, Betaine, Bromocriptine, Calcium Carbonate, Cannabinol, Cinnamon, Corn Oil, Dapagliflozin, Dasatinib Anhydrous, Dextrose, Ecnoglutide, Enclomiphene, Estrone, Fallypride, Fenofibrate, Fluoxetine, Glucagon, Inulin, Konjac Mannan, Metoprolol, Nabilone, Naloxone, Niacin, Olive Oil, Onabotulinumtoxina, Orforglipron, Oxitriptan, Oxytocin, Pioglitazone, Pramlintide, Quercetin, Secretin, Sevoflurane, Sitagliptin, Starch, Sugammadex, Syrup, Tadalafil, Testosterone, Tryptophan, Vancomycin, Vigabatrin, Zinc Sulfate, Zonisamide.

Drug target analysis

Approved (phase 4): 12 · Phase ≥3: 12 · Phased (≥1): 16 · Undrugged: 59

Druggability breadth: 79 of 181 evidence-associated genes (44%) 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
MC4R	BEPRIDIL
HTR2C	PIMOZIDE
RPL27A	GENTAMICIN SULFATE
SCN1A	MEXILETINE HYDROCHLORIDE
SCNN1A	AMILORIDE
SHH	VISMODEGIB
SOS1	IDARUBICIN
SREBF1	CALCIFEDIOL ANHYDROUS
TNKS	NIRAPARIB
CAMK1G	FEDRATINIB
PRMT6	SULFATHIAZOLE
TNNI3K	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HTR2C	276	4
SCN1A	94	4
MC4R	57	4
TNNI3K	20	4
CAMK1G	14	4
TNKS	9	4
SOS1	5	4
SETD2	3	2
SCNN1A	2	4
SMARCA4	2	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BEPRIDIL	4	MC4R, SCN1A
CLOTRIMAZOLE	4	HTR2C, MC4R
IMIPRAMINE	4	HTR2C, MC4R, SCN1A
RIMONABANT	4	MC4R
DESLORATADINE	4	HTR2C, MC4R
DULOXETINE	4	HTR2C, MC4R
SORAFENIB TOSYLATE	4	MC4R
DESERPIDINE	4	MC4R
NAFARELIN	4	MC4R
GRAMICIDIN	4	MC4R
ROSIGLITAZONE	4	MC4R
ROFECOXIB	4	MC4R
ANTAZOLINE	4	MC4R
MODAFINIL	4	MC4R
PIMOZIDE	4	HTR2C, MC4R, SCN1A
AMLODIPINE	4	HTR2C, MC4R
RIFAXIMIN	4	HTR2C, MC4R
CLEMASTINE	4	HTR2C, MC4R
TERFENADINE	4	HTR2C, MC4R
IVACAFTOR	4	MC4R
BREMELANOTIDE	4	MC4R
COSYNTROPIN	4	MC4R
LINAGLIPTIN	4	MC4R
PRENYLAMINE	4	MC4R, SCN1A
METHACYCLINE	4	MC4R
BOSUTINIB	4	HTR2C, MC4R, TNNI3K
ASTEMIZOLE	4	HTR2C, MC4R
FENOTEROL	4	MC4R
SETMELANOTIDE	4	MC4R
CLOMIPRAMINE	4	HTR2C, MC4R

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 11.

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

Symbol	Assays	Type breakdown
HTR2C	1,235	Binding:928, Functional:290, ADMET:14, Unclassified:2, Toxicity:1
MC4R	663	Binding:364, Functional:293, ADMET:6
SOS1	421	Binding:409, Functional:12
SMARCA4	230	Binding:207, ADMET:12, Functional:11
TNKS	226	Binding:223, Functional:3
PRMT6	194	Binding:179, Functional:15
SCN1A	149	Binding:115, Functional:18, ADMET:14, Toxicity:2
CAMK1G	137	Binding:136, Functional:1
TNNI3K	92	Binding:92
RPL27A	90	Binding:90
SETD2	64	Binding:64
TCF4	31	Binding:31
KSR2	28	Binding:28
SHH	27	Binding:23, Functional:4
KAT6B	22	Binding:20, Functional:2
KIF4A	20	Binding:20
SREBF1	17	Binding:17
SLC8A1	9	Binding:8, Functional:1
ANO2	8	Binding:5, ADMET:3
CYFIP1	7	Binding:7
RTN4	7	Binding:7
SCNN1A	6	Binding:4, ADMET:1, Functional:1
ARID1A	6	Binding:6
CHAMP1	6	Binding:6
MACROD2	4	Binding:2, Toxicity:2
GHRL	4	Binding:4
PHF6	4	Binding:4
LEPR	3	Binding:3
FARS2	3	Binding:3
BDNF	2	Binding:2
GPRC5B	2	Binding:2
FBXO11	2	Binding:2
LYPLAL1	2	Binding:2
MRPS22	1	Binding:1
CDKAL1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TCF4	7.6.2.3	ABC-type glutathione-S-conjugate transporter
TNKS	2.4.2.30	NAD+ ADP-ribosyltransferase
UBE2E3	2.3.2.23, 2.3.2.24	E2 ubiquitin-conjugating enzyme, (E3-independent) E2 ubiquitin-conjugating enzyme
CAMK1G	2.7.11.17	Ca2+/calmodulin-dependent protein kinase
MACROD2	3.1.1.106	O-acetyl-ADP-ribose deacetylase
KAT6B	2.3.1.48	histone acetyltransferase
PRMT6	2.1.1.319	type I protein arginine methyltransferase
SETD2	2.1.1.359	[histone H3]-lysine36 N-trimethyltransferase
KSR2	2.7.11.25	mitogen-activated protein kinase kinase kinase
FANCL	2.3.2.27	RING-type E3 ubiquitin transferase
FARS2	6.1.1.20	phenylalanine-tRNA ligase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
MC4R	663
HTR2C	1,235
SCN1A	149
SMARCA4	230
SOS1	421
TNKS	226
CAMK1G	137
PRMT6	194

Pharmacogenomics

Cohort genes with a PharmGKB record: 75; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

27 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)
BEPRIDIL	4	MC4R, SCN1A
CLOTRIMAZOLE	4	HTR2C, MC4R
IMIPRAMINE	4	HTR2C, MC4R, SCN1A
DESLORATADINE	4	HTR2C, MC4R
DULOXETINE	4	HTR2C, MC4R
SORAFENIB TOSYLATE	4	MC4R
DESERPIDINE	4	MC4R
NAFARELIN	4	MC4R
GRAMICIDIN	4	MC4R
ROFECOXIB	4	MC4R
ANTAZOLINE	4	MC4R
MODAFINIL	4	MC4R
PIMOZIDE	4	HTR2C, MC4R, SCN1A
RIFAXIMIN	4	HTR2C, MC4R
CLEMASTINE	4	HTR2C, MC4R
TERFENADINE	4	HTR2C, MC4R
IVACAFTOR	4	MC4R
BREMELANOTIDE	4	MC4R
COSYNTROPIN	4	MC4R
LINAGLIPTIN	4	MC4R
PRENYLAMINE	4	MC4R, SCN1A
METHACYCLINE	4	MC4R
BOSUTINIB	4	HTR2C, MC4R, TNNI3K
ASTEMIZOLE	4	HTR2C, MC4R
FENOTEROL	4	MC4R
SETMELANOTIDE	4	MC4R
CLOMIPRAMINE	4	HTR2C, MC4R

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	12	MC4R, HTR2C, RPL27A, SCN1A, SCNN1A, SHH, SOS1, SREBF1, TNKS, CAMK1G (+2 more)
B	Phased (≥1) drug, not yet approved	4	SMARCA4, TCF4, SETD2, CHAMP1
C	Druggable family + PDB, no drug	7	LEPR, UBE2E3, MACROD2, NEGR1, KSR2, ALPK1, FARS2
D	Druggable family + AlphaFold only, no drug	6	UCP3, GPRC5B, CMYA5, OR6Y1, OR6P1, OR4F21
E	Difficult family or no structure, no drug	46	BDNF, SH2B1, POMC, RGS6, SDCCAG8, SIM1, SLC32A1, SLC8A1, ARID1A, SOX11 (+36 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
POMC	0	MC4R
SIM1	0	MC4R
ARID1A	6	SMARCA4
SOX11	0	SMARCA4
GPRC5B	2	TNNI3K
POGZ	0	CHAMP1
BDNF	2	—
SH2B1	0	—
LEPR	3	—
RGS6	0	—
SDCCAG8	0	—
SLC32A1	0	—
SLC8A1	9	—
SPRY2	0	—
TBCE	0	—
TBX3	0	—
TFAP2B	0	—
ANO2	8	—
UBE2E3	0	—
UCP3	0	—
WWOX	0	—
ZNF248	0	—
SCAPER	0	—
KIF4A	20	—
FBXO11	2	—
CABP5	0	—
CYFIP1	7	—
RTN4	7	—
CMYA5	0	—
MRPS22	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 7,775.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE3	358
PHASE4	351
PHASE2	256
PHASE2/PHASE3	82
PHASE1/PHASE2	53

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02400359	PHASE4	ACTIVE_NOT_RECRUITING	Lorcaserin in Obesity: Identification of CNS Targets Using fMRI
NCT02944500	PHASE4	ACTIVE_NOT_RECRUITING	Saxenda: Underlying Mechanisms and Clinical Outcomes
NCT03024879	PHASE4	ENROLLING_BY_INVITATION	The Effect of Motilin on the Frequency and Amount of Food Intake
NCT03851627	PHASE4	RECRUITING	Effects of Testosterone Undecanoate vs Placebo on Intrahepatic Fat Content in Overweight/Obese Men With T2DM or Prediabetes and Hypogonadism
NCT03938389	PHASE4	ACTIVE_NOT_RECRUITING	The Renin-Angiotensin-Aldosterone System in Adiposity, Blood Pressure and Glucose in African Americans
NCT04297592	PHASE4	ENROLLING_BY_INVITATION	Antibiotic Prophylaxis in High-Risk Arthroplasty Patients
NCT05051436	PHASE4	RECRUITING	The Effects of Mirabegron and Tadalafil on Glucose Tolerance in Prediabetics
NCT05176626	PHASE4	ACTIVE_NOT_RECRUITING	Long-term Effectiveness of the Antiobesity Medication Phentermine
NCT05264727	PHASE4	ACTIVE_NOT_RECRUITING	Glucagon Suppression by Hyperglycemia in the Presence and Absence of Amino Acid Infusion
NCT05320796	PHASE4	RECRUITING	The Bioavailability and Effect on Pouch pH of Esomeprazole After Gastric Bypass
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT05804591	PHASE4	RECRUITING	Pregabalin in the Obese Patients Undergoing Laparoscopic Sleeve Gastrectomy (LSG).
NCT05919797	PHASE4	RECRUITING	Weight Loss Study: Genetics and Response to Naltrexone/Bupropion
NCT05949008	PHASE4	ACTIVE_NOT_RECRUITING	Effect of Metformin, a Drug Used to Treat Diabetes, vs Placebo
NCT05975580	PHASE4	RECRUITING	Pharmacotherapy in Conjunction With Lifestyle Counseling for Management of Weight Regain After Bariatric Surgery
NCT06000462	PHASE4	ACTIVE_NOT_RECRUITING	The Effect of Dapagliflozin on Weight Loss in Obese Adults Without Diabetes
NCT06098079	PHASE4	ACTIVE_NOT_RECRUITING	Effect of Naltrexone Hydrochloride ER and Bupropion Hydrochloride ER Combination (Contrave®/Mysimba®) on Major Adverse Cardiovascular Events (MACE)
NCT06184633	PHASE4	RECRUITING	DUTCH Weight Control in Atrial Fibrillation Study
NCT06191848	PHASE4	RECRUITING	Subcutaneous Tirzepatide Once-weekly in Patients With Obesity and Knee Osteoarthritis (STOP KNEE-OA)
NCT06283381	PHASE4	RECRUITING	The ESG Integrity Study: Effect of Proton Pump Inhibitors on the Structural Integrity of Endoscopic Sleeve Gastroplasty
NCT06287307	PHASE4	NOT_YET_RECRUITING	Semaglutide 2.4mg for Low Responders After Bariatric Surgery
NCT06374875	PHASE4	RECRUITING	Fibrosis Lessens After Metabolic Surgery
NCT06396416	PHASE4	RECRUITING	Obesity Management for Kidney TRANSPLANTation: OK-TRANSPLANT 2
NCT06438146	PHASE4	RECRUITING	LIROH - Liraglutide for Obesity in HIV
NCT06571383	PHASE4	ACTIVE_NOT_RECRUITING	STEP TEENS Weight Maintenance: A Research Study on How Well Semaglutide Helps Teenagers With Excess Body Weight to Lose Weight and Maintain Weight Loss
NCT06606821	PHASE4	RECRUITING	The Effects of Tirzepatide in People With Overweight/Obesity and Coronary Artery Disease
NCT06742710	PHASE4	RECRUITING	Liraglutide Treatment in Obese Infertile PCOS Women
NCT06770049	PHASE4	RECRUITING	Phenotype-Tailored Lifestyle Intervention for Obesity: A Randomized Trial
NCT06801015	PHASE4	ACTIVE_NOT_RECRUITING	Effects of Long-Acting GLP-1 (Glucagon-like Peptide-1) or Dual Incretin (GLP-1 and GIP [Glucose-dependent Insulinotropic Peptide]) Modulation on Gastric Motor Functions
NCT06809166	PHASE4	RECRUITING	Metabolic and Behavioural Effects of CONTRAVE as Potential Mechanisms of Weight Loss in Adults With Obesity
NCT06814938	PHASE4	RECRUITING	A Study of a Novel Precision Medicine Approach For Obesity
NCT06845345	PHASE4	ENROLLING_BY_INVITATION	Effect of an Early Time Restricted Eating Mediterranean Diet Compared to Naltrexone/Bupropion on Liver Fibrosis in People With Cardiometabolic Risk Factors in a Hospital Outpatient Clinic (MEDFAST-study)
NCT06852391	PHASE4	RECRUITING	JOULE - Metabolic Adaptation to Weight Loss in Response to a Behavioural Lifestyle Program With or Without Semaglutide in Adolescents With Obesity
NCT06854614	PHASE4	ACTIVE_NOT_RECRUITING	Sequential or CombinaTion Anti-obesitY Medication With Muscle Preservation for Weight Loss and MaintEnance: A PragmAtic Randomized CoNtrolled Trial (STAY-LEAN Trial)
NCT06857942	PHASE4	RECRUITING	A Study to Investigate the Effectiveness of Tirzepatide (LY3298176) Following Initiation of Ixekizumab (LY2439821) in Participants With Moderate-to-Severe Plaque PsO and Obesity or Overweight in Clinical Practice (TOGETHER AMPLIFY-PsO)
NCT06861439	PHASE4	ACTIVE_NOT_RECRUITING	GLP-1s to Enhance Lasting Optimal Weight
NCT06864026	PHASE4	RECRUITING	A Study to Investigate Effectiveness of Tirzepatide Following Initiation of Ixekizumab in Participants With Active Psoriatic Arthritis and Overweight or Obesity in Clinical Practice (TOGETHER AMPLIFY-PsA)
NCT06901245	PHASE4	RECRUITING	Tirzepatide in PWS, HO and GNSO
NCT06992726	PHASE4	NOT_YET_RECRUITING	Improvement of Fish Oil in Obesity With Mild Cognitive Impairment
NCT07057310	PHASE4	ENROLLING_BY_INVITATION	Aging Well: Targeting Obesity With GLP-1 Agonists to Enhance Physical and Vascular Health in Postmenopausal Women

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ORLISTAT	4	20
RIMONABANT	4	20
SIBUTRAMINE	4	19
EXENATIDE	4	9
CHOLECALCIFEROL	4	7
ERGOCALCIFEROL	4	4
METFORMIN	4	4
ROSIGLITAZONE	4	4
AMLODIPINE	4	3
ENOXAPARIN SODIUM	4	3
DESFLURANE	4	2
FENOFIBRATE	4	2
INSULIN DETEMIR	4	2
IRBESARTAN	4	2
LOSARTAN	4	2
PIOGLITAZONE	4	2
TESTOSTERONE	4	2
ZONISAMIDE	4	2
ATORVASTATIN	4	1
CASPOFUNGIN	4	1
DAPSONE	4	1
DIETHYLPROPION	4	1
ETHAMBUTOL	4	1
HYDROCHLOROTHIAZIDE	4	1
INFLIXIMAB	4	1
INSULIN HUMAN, ISOPHANE	4	1
MICAFUNGIN	4	1
OCTREOTIDE ACETATE	4	1
PENTOXIFYLLINE	4	1
SULFAMETHOXAZOLE	4	1