Gestational diabetes

Summary

Gestational diabetes (MONDO:0005406) is a disease with 6 cohort genes (127 GWAS associations across 26 studies) and 603 clinical trials. Top therapeutic interventions include insulin human, glyburide, and acetylcholine.

At a glance

• Cohort genes: 6
• GWAS associations: 127
• ClinVar variants: 6
• Clinical trials: 603

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	gestational diabetes
Mondo ID	MONDO:0005406
EFO	EFO:0004593
MeSH	D016640
DOID	DOID:11714
ICD-10-CM	O24.4
ICD-11	1320503631
NCIT	C34942
SNOMED CT	11687002
UMLS	C0085207
MedGen	38815
Is cancer (heuristic)	no

Also known as: diabetes in pregnancy · gestational diabetes mellitus · maternal gestational diabetes mellitus

Data availability: 6 ClinVar variants · 127 GWAS associations (26 studies).

Disease family

Classification path: disease › human disease › disease by body system or component › digestive system disorder › pancreas disorder › endocrine pancreas disorder › diabetes mellitus › gestational diabetes

Related subtypes (7): type 1 diabetes mellitus, type 2 diabetes mellitus, maternally-inherited diabetes and deafness, diabetic ketoacidosis, monogenic diabetes, type 5 diabetes mellitus, cystic fibrosis-related diabetes

Genetics & variants

GWAS landscape

127 GWAS associations across 26 studies. Top hits map to 33 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs10830963	2e-156	MTNR1B	C	0.69
rs10466351	7e-78	SNRPGP16 - MTNR1B	T	0.45
rs9368222	2e-46	CDKAL1	A	0.26
rs34872471	8e-22	TCF7L2	T	0.85
rs61160304	3e-21	FSCN3 - PAX4	T	0.35
rs7903146	2e-19	TCF7L2	T	0.18
rs17085675	6e-19	CAST, PCSK1	A	1.14
rs9275599	1e-18	MTCO3P1 - HLA-DQB3	C	0.82
rs1820176	2e-17	CAST	?	0.16
rs10758593	1e-16	GLIS3	A	0.18
rs7754840	7e-16	CDKAL1	C	1.52
rs36090025	4e-15	TCF7L2	?
rs10963767	4e-15	ADAMTSL1	C	0.14
rs9348441	2e-14	CDKAL1	A	1.13
rs1260326	3e-14	GCKR	T	0.89
rs10830962	2e-13	SNRPGP16 - MTNR1B	G	1.45
rs76895963	3e-13	CCND2-AS1, CCND2	T	1.4
rs7766070	5e-13	CDKAL1	?
rs780093	8e-13	GCKR	?	0.12
Chr16:81534790	6e-12		A	0.12
rs7925879	3e-11	ROBO3	G	0.11
rs3786897	7e-11	PEPD	G	0.11
rs13266634	3e-10	SLC30A8	?
rs7756992	4e-10	CDKAL1	A	0.91
rs6798189	5e-10	ADCY5	?	0.14
rs4811839	6e-10	MTND1P9, RAE1	G	0.1
rs2236835	8e-10	PAX7	A	0.1
rs2237897	2e-09	KCNQ1	C	1.18
rs10811662	4e-09	CDKN2B-AS1	G	1.14
rs1402837	5e-09	SPC25	?	0.12

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90296696	Elliott A	2024	12,332	131,109	Distinct and shared genetic architectures of gestational diabetes mellitus and type 2 diabetes.
GCST90454236	Pujol Gualdo N	2025	12,224	288,329	Atlas of genetic and phenotypic associations across 42 female reproductive health diagnoses.
GCST90566419	Gu Y	2025	12,024	67,845	Genetic architecture and risk prediction of gestational diabetes mellitus in Chinese pregnancies.
GCST90245820	Changalidis AI	2022	7,395	333,819	Aggregation of Genome-Wide Association Data from FinnGen and UK Biobank Replicates Multiple Risk Loci for Pregnancy Complications.
GCST90727187	Kim HI	2026	4,424	39,602	Exome sequencing and analysis of 44,028 British South Asians enriched for high autozygosity.
GCST90727296	Kim HI	2026	3,971	40,055	Exome sequencing and analysis of 44,028 British South Asians enriched for high autozygosity.
GCST90297786	Zhen J	2024	3,317	19,565	Genome-wide association and Mendelian randomisation analysis among 30,699 Chinese pregnant women identifies novel genetic and molecular risk factors for gestational diabetes and glycaemic traits.
GCST90557999	Lee K	2024	1,323	6,744	Metabolomic and genetic architecture of gestational diabetes subtypes.
GCST90043951	Jiang L	2021	864	6,977	A generalized linear mixed model association tool for biobank-scale data.
GCST90079142	Backman JD	2021	845	7,001	Exome sequencing and analysis of 454,787 UK Biobank participants.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	2
Tier 2: splice/UTR	3
Tier 3: regulatory	2
Tier 4: intronic/intergenic	43

MAF distribution

Bucket	Variants
common (>=0.05)	49
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	1

Functional consequences

Consequence	Count
intron_variant	33
intergenic_variant	7
3_prime_UTR_variant	3
missense_variant	2
non_coding_transcript_exon_variant	2
regulatory_region_variant	2
unknown	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs10830963	11	92975544	C>G,T	0.05	intron_variant	MTNR1B	2e-156	Tier 4: intronic/intergenic
rs10466351	11	92964815	C>G,T	0.05	intron_variant	SNRPGP16 - MTNR1B	7e-78	Tier 4: intronic/intergenic
rs9368222	6	20686765	C>A,T	0.05	intron_variant	CDKAL1	2e-46	Tier 4: intronic/intergenic
rs34872471	10	112994312	T>C	0.05	intron_variant	TCF7L2	8e-22	Tier 4: intronic/intergenic
rs61160304	7	127609605	C>T	0.05	intergenic_variant	FSCN3 - PAX4	3e-21	Tier 4: intronic/intergenic
rs7903146	10	112998590	C>G,T	0.05	intron_variant	TCF7L2	2e-19	Tier 4: intronic/intergenic
rs17085675	5	96391960	A>T	0.05	3_prime_UTR_variant	CAST, PCSK1	6e-19	Tier 2: splice/UTR
rs9275599	6	32714652	C>T	0.05	intergenic_variant	MTCO3P1 - HLA-DQB3	1e-18	Tier 4: intronic/intergenic
rs1820176	5	96360881	T>C	0.05	intron_variant	CAST	2e-17	Tier 4: intronic/intergenic
rs10758593	9	4292083	G>A	0.05	intron_variant	GLIS3	1e-16	Tier 4: intronic/intergenic
rs7754840	6	20661019	G>A,C,T	0.445	intron_variant	CDKAL1	7e-16	Tier 4: intronic/intergenic
rs36090025	10	113014674	A>C,G	0.05	intron_variant	TCF7L2	4e-15	Tier 4: intronic/intergenic
rs10963767	9	18797922	T>C,G	0.05	intron_variant	ADAMTSL1	4e-15	Tier 4: intronic/intergenic
rs9348441	6	20680447	T>A	0.05	intron_variant	CDKAL1	2e-14	Tier 4: intronic/intergenic
rs1260326	2	27508073	T>A,C,G	0.05	missense_variant	GCKR	3e-14	Tier 1: coding
rs10830962	11	92965261	C>A,G,T	0.43	intron_variant	SNRPGP16 - MTNR1B	2e-13	Tier 4: intronic/intergenic
rs76895963	12	4275678	T>C,G	0.05	non_coding_transcript_exon_variant	CCND2-AS1, CCND2	3e-13	Tier 4: intronic/intergenic
rs7766070	6	20686342	C>A,G,T	0.05	intron_variant	CDKAL1	5e-13	Tier 4: intronic/intergenic
rs780093	2	27519736	T>A,C,G	0.05	intron_variant	GCKR	8e-13	Tier 4: intronic/intergenic
Chr16:81534790							6e-12	Tier 4: intronic/intergenic
rs7925879	11	124870795	A>G	0.05	intron_variant	ROBO3	3e-11	Tier 4: intronic/intergenic
rs3786897	19	33402102	A>G,T	0.05	intron_variant	PEPD	7e-11	Tier 4: intronic/intergenic
rs13266634	8	117172544	C>A,T	0.05	missense_variant	SLC30A8	3e-10	Tier 1: coding
rs7756992	6	20679478	A>G,T	0.05	intron_variant	CDKAL1	4e-10	Tier 4: intronic/intergenic
rs6798189	3	123376465	G>A	0.05	intron_variant	ADCY5	5e-10	Tier 4: intronic/intergenic
rs4811839	20	57357551	T>A,G	0.05	non_coding_transcript_exon_variant	MTND1P9, RAE1	6e-10	Tier 4: intronic/intergenic
rs2236835	1	18663757	G>A,C,T	0.05	intron_variant	PAX7	8e-10	Tier 4: intronic/intergenic
rs2237897	11	2837316	C>T	0.05	intron_variant	KCNQ1	2e-09	Tier 4: intronic/intergenic
rs10811662	9	22134254	G>A,C	0.05	intergenic_variant	CDKN2B-AS1	4e-09	Tier 4: intronic/intergenic
rs1402837	2	168900844	C>A,G,T	0.05	intergenic_variant	SPC25	5e-09	Tier 4: intronic/intergenic

ClinVar germline variants

6 retrieved; paginated sample, class counts are floors:

4 pathogenic, 1 pathogenic/likely pathogenic, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
129140	NM_000162.5(GCK):c.1112G>T (p.Cys371Phe)	GCK	Pathogenic	reviewed by expert panel
129144	NM_000162.5(GCK):c.544G>A (p.Val182Met)	GCK	Pathogenic	reviewed by expert panel
129145	NM_000162.5(GCK):c.616A>C (p.Thr206Pro)	GCK	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
129146	NM_000162.5(GCK):c.706G>A (p.Glu236Lys)	GCK	Pathogenic	criteria provided, single submitter
36258	NM_000162.5(GCK):c.787T>C (p.Ser263Pro)	GCK	Pathogenic	reviewed by expert panel
307464	NM_000545.8(HNF1A):c.*197G>T	C12orf43	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GCK	Orphanet:552	MODY
GCK	Orphanet:79299	Congenital glucokinase-related hyperinsulinism
GCK	Orphanet:99885	Isolated permanent neonatal diabetes mellitus

Cohort genes → proteins

6 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	4
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CDH18	HGNC:1757	ENSG00000145526	Q13634	Cadherin-18	gwas
CDKAL1	HGNC:21050	ENSG00000145996	Q5VV42	Threonylcarbamoyladenosine tRNA methylthiotransferase	gwas
C12orf43	HGNC:25719	ENSG00000157895	Q96C57	Protein CUSTOS	clinvar
IGF2BP2	HGNC:28867	ENSG00000073792	Q9Y6M1	Insulin-like growth factor 2 mRNA-binding protein 2	gwas
GCK	HGNC:4195	ENSG00000106633	P35557	Hexokinase-4	clinvar
MTNR1B	HGNC:7464	ENSG00000134640	P49286	Melatonin receptor type 1B	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CDH18	Cadherin-18	Cadherins are calcium-dependent cell adhesion proteins.
CDKAL1	Threonylcarbamoyladenosine tRNA methylthiotransferase	Catalyzes the methylthiolation of N6-threonylcarbamoyladenosine (t(6)A), leading to the formation of 2-methylthio-N6-threonylcarbamoyladenosine (ms(2)t(6)A) at position 37 in tRNAs that read codons beginning with adenine.
C12orf43	Protein CUSTOS	Plays a role in the regulation of Wnt signaling pathway during early development.
IGF2BP2	Insulin-like growth factor 2 mRNA-binding protein 2	RNA-binding factor that recruits target transcripts to cytoplasmic protein-RNA complexes (mRNPs).
GCK	Hexokinase-4	Catalyzes the phosphorylation of hexose, such as D-glucose, D-fructose and D-mannose, to hexose 6-phosphate (D-glucose 6-phosphate, D-fructose 6-phosphate and D-mannose 6-phosphate, respectively).
MTNR1B	Melatonin receptor type 1B	High affinity receptor for melatonin.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 4 · Druggable fraction: 0.33

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
Kinase	1	4.6×	0.339
GPCR	1	4.0×	0.339
Other/Unknown	4	1.2×	0.458

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CDH18	Other/Unknown	no		Cadherin_Y-type_LIR, Cadherin-like_dom, Cadherin-like_sf
CDKAL1	Other/Unknown	no		TRAM_dom, Methylthiotransferase, MiaB-like_arc_euk
C12orf43	Other/Unknown	no		CUSTOS
IGF2BP2	Other/Unknown	no		RRM_dom, KH_dom, KH_dom_type_1
GCK	Kinase	yes	2.7.1.1	Hexokinase, Hexokinase_BS, Hexokinase_N
MTNR1B	GPCR	yes		Melatonin_rcpt, GPCR_Rhodpsn, Mel_1A/1B_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)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
buccal mucosa cell	2
islet of Langerhans	2
cerebellar vermis	1
middle temporal gyrus	1
paraflocculus	1
calcaneal tendon	1
ganglionic eminence	1
oocyte	1
prefrontal cortex	1
secondary oocyte	1
adrenal tissue	1
ventricular zone	1
adenohypophysis	1
pituitary gland	1
deltoid	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CDH18	170	broad	marker	middle temporal gyrus, cerebellar vermis, paraflocculus
CDKAL1	201	ubiquitous	marker	buccal mucosa cell, calcaneal tendon, ganglionic eminence
C12orf43	266	ubiquitous	marker	secondary oocyte, oocyte, prefrontal cortex
IGF2BP2	252	ubiquitous	marker	buccal mucosa cell, adrenal tissue, ventricular zone
GCK	155	tissue_specific	marker	pituitary gland, adenohypophysis, islet of Langerhans
MTNR1B	46		yes	primordial germ cell in gonad, islet of Langerhans, deltoid

Protein interactions among cohort

Intra-cohort edges: 4.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CDKAL1	2,724
IGF2BP2	2,594
GCK	2,245
MTNR1B	1,351
CDH18	889
C12orf43	621

Intra-cohort edges

A	B	Sources
CDKAL1	IGF2BP2	string_interaction
CDKAL1	MTNR1B	string_interaction
GCK	MTNR1B	string_interaction
IGF2BP2	MTNR1B	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 3 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GCK	P35557	35
MTNR1B	P49286	5
IGF2BP2	Q9Y6M1	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CDKAL1	Q5VV42	82.72
CDH18	Q13634	77.57
C12orf43	Q96C57	64.08

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 20. Enrichment computed across 6 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
Defective GCK causes maturity-onset diabetes of the young 2 (MODY2)	1	2284.0×	0.009	GCK
Insulin-like Growth Factor-2 mRNA Binding Proteins (IGF2BPs/IMPs/VICKZs) bind RNA	1	571.0×	0.018	IGF2BP2
Regulation of gene expression in beta cells	1	103.8×	0.036	GCK
FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes	1	76.1×	0.036	GCK
Regulation of Glucokinase by Glucokinase Regulatory Protein	1	71.4×	0.036	GCK
Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC)	1	71.4×	0.036	GCK
tRNA processing	1	71.4×	0.036	CDKAL1
tRNA modification in the nucleus and cytosol	1	58.6×	0.036	CDKAL1
Glycolysis	1	57.1×	0.036	GCK
Adherens junctions interactions	1	49.6×	0.036	CDH18
Cell-cell junction organization	1	49.6×	0.036	CDH18
Cell junction organization	1	37.4×	0.044	CDH18
Cell-Cell communication	1	27.5×	0.055	CDH18
Class A/1 (Rhodopsin-like receptors)	1	14.8×	0.094	MTNR1B
GPCR ligand binding	1	12.8×	0.101	MTNR1B
GPCR downstream signalling	1	8.7×	0.128	MTNR1B
Metabolism of RNA	1	8.3×	0.128	CDKAL1
Signaling by GPCR	1	8.0×	0.128	MTNR1B
G alpha (i) signalling events	1	7.8×	0.128	MTNR1B
Signal Transduction	1	2.0×	0.404	MTNR1B

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
regulation of insulin secretion	2	130.6×	0.005	GCK, MTNR1B
tRNA methylthiolation	1	2808.7×	0.009	CDKAL1
Spemann organizer formation	1	936.2×	0.009	C12orf43
cold-induced thermogenesis	1	936.2×	0.009	IGF2BP2
maintenance of translational fidelity	1	936.2×	0.009	CDKAL1
positive regulation of circadian sleep/wake cycle, non-REM sleep	1	702.2×	0.009	MTNR1B
regulation of neuronal action potential	1	702.2×	0.009	MTNR1B
glucose homeostasis	2	43.5×	0.009	GCK, MTNR1B
RNA stabilization	1	561.7×	0.010	IGF2BP2
negative regulation of receptor guanylyl cyclase signaling pathway	1	468.1×	0.010	MTNR1B
glucose catabolic process	1	401.2×	0.010	GCK
negative regulation of transmission of nerve impulse	1	401.2×	0.010	MTNR1B
positive regulation of transmission of nerve impulse	1	401.2×	0.010	MTNR1B
regulation of potassium ion transport	1	312.1×	0.012	GCK
negative regulation of vasoconstriction	1	280.9×	0.012	MTNR1B
NADP+ metabolic process	1	255.3×	0.012	GCK
cellular response to leptin stimulus	1	255.3×	0.012	GCK
CRD-mediated mRNA stabilization	1	234.1×	0.012	IGF2BP2
glucose 6-phosphate metabolic process	1	216.1×	0.012	GCK
negative regulation of cytosolic calcium ion concentration	1	216.1×	0.012	MTNR1B
regulation of glycolytic process	1	200.6×	0.012	GCK
positive regulation of glycogen biosynthetic process	1	165.2×	0.014	GCK
negative regulation of gluconeogenesis	1	133.8×	0.016	GCK
calcium ion import	1	133.8×	0.016	GCK
canonical glycolysis	1	117.0×	0.018	GCK
intracellular glucose homeostasis	1	96.8×	0.021	GCK
adherens junction organization	1	85.1×	0.022	CDH18
negative regulation of insulin secretion	1	82.6×	0.022	MTNR1B
calcium-dependent cell-cell adhesion	1	80.2×	0.022	CDH18
cell-cell junction assembly	1	73.9×	0.023	CDH18

Therapeutics

Drugs indicated for this disease

0 approved, 10 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Acarbose	Phase 3 (in late-stage trials)
Cholecalciferol	Phase 3 (in late-stage trials)
Empagliflozin	Phase 3 (in late-stage trials)
Glyburide	Phase 3 (in late-stage trials)
Insulin Aspart	Phase 3 (in late-stage trials)
Insulin Human	Phase 3 (in late-stage trials)
Insulin Pork	Phase 3 (in late-stage trials)
Insulin Susp Isophane Beef	Phase 3 (in late-stage trials)
Metformin	Phase 3 (in late-stage trials)
Ursodiol	Phase 3 (in late-stage trials)

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

Drug target analysis

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

Druggability breadth: 4 of 6 evidence-associated genes (67%) 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
MTNR1B	AGOMELATINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MTNR1B	7	4
GCK	5	2
CDH18	0	0
CDKAL1	0	0
C12orf43	0	0
IGF2BP2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
AGOMELATINE	4	MTNR1B
RAMELTEON	4	MTNR1B
TASIMELTEON	4	MTNR1B
CIANIDANOL	4	MTNR1B
MELATONIN	4	MTNR1B
DOPAMINE	4	MTNR1B
PIRAGLIATIN	2	GCK
NERIGLIATIN	2	GCK
PF-04991532	2	GCK
AZD-1656	2	GCK
MK-0941 FREE BASE	2	GCK
MEBUFOTENIN	2	MTNR1B

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
MTNR1B	311	Binding:196, Functional:115
GCK	228	Binding:226, ADMET:1, Functional:1
IGF2BP2	3	Binding:3
CDKAL1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
GCK	2.7.1.1	hexokinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
GCK	228
MTNR1B	311

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

12 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)
AGOMELATINE	4	MTNR1B
RAMELTEON	4	MTNR1B
TASIMELTEON	4	MTNR1B
CIANIDANOL	4	MTNR1B
MELATONIN	4	MTNR1B
DOPAMINE	4	MTNR1B
PIRAGLIATIN	2	GCK
NERIGLIATIN	2	GCK
PF-04991532	2	GCK
AZD-1656	2	GCK
MK-0941 FREE BASE	2	GCK
MEBUFOTENIN	2	MTNR1B

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	MTNR1B
B	Phased (≥1) drug, not yet approved	1	GCK
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	4	CDH18, CDKAL1, C12orf43, IGF2BP2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CDH18	0	—
CDKAL1	1	—
C12orf43	0	—
IGF2BP2	3	—

Clinical trials & evidence

Clinical trials

Clinical trials: 603.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	534
PHASE4	27
PHASE3	17
PHASE2	9
EARLY_PHASE1	7
PHASE2/PHASE3	3
PHASE1/PHASE2	3
PHASE1	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03527537	PHASE4	ACTIVE_NOT_RECRUITING	Gestational Diabetes and Pharmacotherapy (GAP)
NCT04407650	PHASE4	ACTIVE_NOT_RECRUITING	Ursodeoxycholic Acid vs Metformin in Gestational Diabetes Mellitus
NCT05482789	PHASE4	RECRUITING	Exenatide Pharmacokinetics and Pharmacodynamics in Gestational Diabetes
NCT06445946	PHASE4	RECRUITING	DECIDE: A Comparative Effectiveness Trial of Metformin Versus Insulin for the Treatment of Gestational Diabetes
NCT06781775	PHASE4	RECRUITING	GDM: Insulin with or Without Metformin?
NCT00160485	PHASE4	WITHDRAWN	Glyburide Compared to Insulin in the Management of White’s Classification A2 Gestational Diabetes
NCT00572689	PHASE4	WITHDRAWN	Pilot Study of Exenatide Pharmacokinetics and Pharmacodynamics in Gestational Diabetes
NCT00744965	PHASE4	COMPLETED	Treatment of Mild Gestational Diabetes With Glyburide Versus Placebo
NCT00813657	PHASE4	COMPLETED	Resistance Exercise Training During Pregnancy: a Randomized Controlled Trial
NCT00883259	PHASE4	UNKNOWN	Metformin and Gestational Diabetes in High-risk Patients: a RCTs
NCT01240785	PHASE4	COMPLETED	Metformin Versus Insulin in Gestational Diabetes
NCT01511835	PHASE4	UNKNOWN	Efficacy of Myo-inositol in Preventing Gestational Diabetes in High-risk Pregnant Women
NCT01563120	PHASE4	COMPLETED	A Comparison Between Two Oral Hypoglycemics - Metformin and Glybenclamide for the Treatment of Gestational Diabetes Mellitus
NCT01613807	PHASE4	COMPLETED	Humalog® Mix50/50(tm) as a Treatment for Gestational Diabetes
NCT01795248	PHASE4	COMPLETED	The Impact of Liraglutide on Glucose Tolerance and the Risk of Type 2 Diabetes in Women With Previous Pregnancy-induced Diabetes
NCT01947699	PHASE4	WITHDRAWN	Glycemic Profile in Women With Gestational Diabetes Treated With Glyburide
NCT01997762	PHASE4	UNKNOWN	Can Resveratrol Improve Insulin Sensitivity and Preserve Beta Cell Function Following Gestational Diabetes?
NCT02091336	PHASE4	UNKNOWN	Oral Antidiabetic Agents in Pregnancy
NCT02355197	PHASE4	COMPLETED	Antioxidants in Gestational Diabetes
NCT02394158	PHASE4	UNKNOWN	Preventing Recurrent Gestational Diabetes With Metformin
NCT02508844	PHASE4	COMPLETED	Effect of Probiotics (Vivomixx®) on Weight, Microbiota and Glucose Tolerance in Obese Pregnant Women and Their Newborn
NCT02590016	PHASE4	UNKNOWN	Glucose Control During Labour in Gestational Diabetes Mellitus With Insulin Treatment: A Randomized Controlled Trial
NCT03029702	PHASE4	COMPLETED	Metabolic Analysis for Treatment Choice in Gestational Diabetes Mellitus
NCT03138616	PHASE4	UNKNOWN	The Impact of Vitamin D Supplementation on Glucose Metabolism in Chinese Women With Former Gestational Diabetes Mellitus
NCT03955107	PHASE4	UNKNOWN	The Effect of Continuous Glucose Monitoring on Glycemic Control and Pregnancy Outcomes in Gestational Diabetes Mellitus
NCT05393843	PHASE4	TERMINATED	Prevention of Maternal and Fetal Metabolic Complications With Diet and Nutraceutical Supplementation in Pregnant Women Affected by Gestational Diabetes: a Randomized, Double-blind Placebo Controlled Trial.
NCT05922033	PHASE4	COMPLETED	Patient Versus Provider-led Titration of Insulin for Glycemic Control in Gestational Diabetes (EMPOWER)
NCT02947503	PHASE3	RECRUITING	Pregnancy Outcomes: Effects of Metformin Study (POEM Study)
NCT05852054	PHASE3	ACTIVE_NOT_RECRUITING	Supporting Transitions to Primary Care Among Under-resourced, Postpartum Women (STEP-UP)
NCT00065130	PHASE3	COMPLETED	Safety and Efficacy of Insulin Aspart vs. Regular Human Insulin in Gestational Diabetes
NCT00414245	PHASE3	UNKNOWN	Metformin for the Treatment of Diabetes in Pregnancy
NCT00994812	PHASE3	COMPLETED	The Effects of Metformin on Pregnancy and Miscarriage Rates in Polycystic Ovary Syndrome (PCOS)
NCT01087866	PHASE2/PHASE3	COMPLETED	Metformin Versus Insulin in the Treatment of Gestational Diabetes Mellitus
NCT01215331	PHASE3	COMPLETED	Gestational Diabetes: Insulin or Oral Hypoglycemic Agents?
NCT01234649	PHASE3	COMPLETED	Combined Liraglutide and Metformin Therapy in Women With Previous Gestational Diabetes Mellitus (GDM)
NCT01589757	PHASE2/PHASE3	COMPLETED	MAIN STUDY: Low Glycaemic Index (GI) Diet in the Management of GDM SUB-STUDY: The Breast Milk Sub-Study
NCT01855763	PHASE2/PHASE3	UNKNOWN	Metformin Treatment in Gestational Diabetes and Noninsulin Dependent Diabetes in Pregnancy in a Developing Country
NCT02080377	PHASE3	COMPLETED	A Feasibility Study Looking at the Use of Glibenclamide and metfoRmin Versus stAndard Care in gEstational diabeteS
NCT02275845	PHASE3	UNKNOWN	Medico-GDM Trial - Metformine to Prevent Gestational Diabetes Mellitus
NCT02478762	PHASE3	TERMINATED	Glycemic Objectives of Women With Gestational Diabetes Mellitus

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
INSULIN HUMAN	4	19
GLYBURIDE	4	10
ACETYLCHOLINE	4	2
EXENATIDE	4	2
METFORMIN	4	2
URSODIOL	4	2
ASCORBIC ACID	4	1
CHOLINE	4	1
ERGOCALCIFEROL	4	1
FERROUS FUMARATE	4	1
FISH OIL	4	1
FOLIC ACID	4	1
INSULIN ASPART	4	1
INSULIN DETEMIR	4	1
INSULIN LISPRO	4	1
LIRAGLUTIDE	4	1
MAGNESIUM CITRATE	4	1
INOSITOL	3	7
ICOSAPENT	3	1
POWDERED CELLULOSE	3	1
RESVERATROL	3	1
SELENIUM	3	1
CHOLESTEROL	2	1
GUAR GUM	2	1
URIC ACID	2	1
CHEMBL1950780	0	5
CHEMBL439305	0	1
CHEMBL4524066	0	1
CHEMBL4645029	0	1
CHEMBL4785366	0	1