GMDS

Summary

GMDS (GDP-mannose 4,6-dehydratase, HGNC:4369) is a protein-coding gene on chromosome 6p25.3, encoding GDP-mannose 4,6 dehydratase (O60547). Catalyzes the conversion of GDP-D-mannose to GDP-4-dehydro-6-deoxy-D-mannose.

GDP-mannose 4,6-dehydratase (GMD; EC 4.2.1.47) catalyzes the conversion of GDP-mannose to GDP-4-keto-6-deoxymannose, the first step in the synthesis of GDP-fucose from GDP-mannose, using NADP+ as a cofactor. The second and third steps of the pathway are catalyzed by a single enzyme, GDP-keto-6-deoxymannose 3,5-epimerase, 4-reductase, designated FX in humans (MIM 137020).

Source: NCBI Gene 2762 — RefSeq curated summary.

At a glance

• GWAS associations: 62
• Clinical variants (ClinVar): 73 total — 1 pathogenic, 1 likely-pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001500

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4369
Approved symbol	GMDS
Name	GDP-mannose 4,6-dehydratase
Location	6p25.3
Locus type	gene with protein product
Status	Approved
Aliases	GMD, SDR3E1
Ensembl gene	ENSG00000112699
Ensembl biotype	protein_coding
OMIM	602884
Entrez	2762

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 9 protein_coding, 6 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000380805, ENST00000380815, ENST00000467288, ENST00000476972, ENST00000486793, ENST00000530075, ENST00000530459, ENST00000530927, ENST00000531690, ENST00000533279, ENST00000851212, ENST00000851213, ENST00000920350, ENST00000920351, ENST00000950952, ENST00000950953, ENST00000950954

RefSeq mRNA: 2 — MANE Select: NM_001500 NM_001253846, NM_001500

CCDS: CCDS4474, CCDS58994

Canonical transcript exons

ENST00000380815 — 11 exons

Exon	Start	End
ENSE00000973296	2124687	2124731
ENSE00000973297	2117469	2117556
ENSE00000973298	2115771	2115880
ENSE00001486507	2245321	2245605
ENSE00003479574	1624472	1624540
ENSE00003513379	1623806	1624231
ENSE00003535188	1742468	1742586
ENSE00003544331	1930103	1930230
ENSE00003625535	1959867	1959971
ENSE00003651460	1726416	1726512
ENSE00003673449	1960774	1960966

Expression profiles

Bgee: expression breadth ubiquitous, 264 present calls, max score 99.05.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.2597 / max 362.0980, expressed in 1801 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
71359	15.1002	1798
71360	2.5669	1255
71349	0.1924	60
71358	0.1774	63
71348	0.1328	52
71350	0.0696	31
71355	0.0206	11

Top tissues by expression

289 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	99.05	gold quality
mucosa of transverse colon	UBERON:0004991	98.67	gold quality
lower esophagus mucosa	UBERON:0035834	98.53	gold quality
descending thoracic aorta	UBERON:0002345	97.72	gold quality
rectum	UBERON:0001052	97.55	gold quality
thoracic aorta	UBERON:0001515	97.32	gold quality
ascending aorta	UBERON:0001496	97.25	gold quality
saliva-secreting gland	UBERON:0001044	97.24	gold quality
duodenum	UBERON:0002114	97.05	gold quality
minor salivary gland	UBERON:0001830	96.91	gold quality
palpebral conjunctiva	UBERON:0001812	96.72	gold quality
aorta	UBERON:0000947	96.57	gold quality
colonic mucosa	UBERON:0000317	96.43	gold quality
right coronary artery	UBERON:0001625	96.24	gold quality
mucosa of sigmoid colon	UBERON:0004993	96.19	gold quality
popliteal artery	UBERON:0002250	96.11	gold quality
tibial artery	UBERON:0007610	96.09	gold quality
pancreatic ductal cell	CL:0002079	95.97	gold quality
ileal mucosa	UBERON:0000331	95.66	gold quality
jejunal mucosa	UBERON:0000399	95.61	gold quality
esophagus squamous epithelium	UBERON:0006920	95.23	gold quality
esophagus mucosa	UBERON:0002469	94.89	gold quality
mouth mucosa	UBERON:0003729	94.83	gold quality
left coronary artery	UBERON:0001626	94.77	gold quality
cartilage tissue	UBERON:0002418	94.77	gold quality
epithelium of esophagus	UBERON:0001976	94.58	gold quality
coronary artery	UBERON:0001621	94.07	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.03	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.94	gold quality
transverse colon	UBERON:0001157	93.86	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	54.21
E-CURD-114	yes	31.81
E-GEOD-125970	yes	22.18
E-HCAD-1	yes	20.24
E-HCAD-4	yes	15.95
E-MTAB-8410	yes	10.17
E-CURD-112	yes	9.01
E-GEOD-84465	yes	6.83
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting GMDS, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-889-3P	99.40	69.76	2103
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-4758-3P	99.12	63.96	869
HSA-MIR-8070	99.07	69.30	1303
HSA-MIR-5583-3P	99.06	65.68	1018
HSA-MIR-4695-5P	99.06	64.87	1151
HSA-MIR-3146	98.85	66.77	601
HSA-MIR-6847-5P	97.93	66.74	1808
HSA-MIR-6502-3P	97.86	65.43	569
HSA-MIR-4749-5P	92.16	62.26	179
HSA-MIR-4706	89.76	60.23	156

Literature-anchored findings (GeneRIF, showing 10)

• FX takes part in the cascade of events leading to the extravasation of activated lymphocytes. (PMID:11831876)
• Deficiency of GMDS leads to escape from natural killer cell-mediated tumor surveillance through modulation of TRAIL signaling. (PMID:19361506)
• Results indicate that GMDS regulates the formation of secondary complex II from the primary DISC independent of direct fucosylation of death receptors. (PMID:22027835)
• GMD inhibits tankyrase 1 poly(ADP-ribose) polymerase activity in vitro, dependent on the GMD tankyrase 1 binding motif. In vivo, depletion of GMD led to degradation of tankyrase 1, dependent on the catalytic PARP activity of tankyrase 1. (PMID:22645305)
• Fx enzyme and GDP-L-Fuc Tr overexpression in the tumur tissue of colorectal cancer (CRC) patients suggests that GDP-L-Fuc transport to the Golgi apparatus may be an important factor associated with increased alpha(1,6)fucosylation in CRC. (PMID:23730929)
• These data demonstrate involvement of GMDS mutation in the progression of colorectal cancer. (PMID:23922970)
• Data indicate three loci associated with primary open-angle glaucoma (POAG) were located upstream of ATP binding cassette transporter 1 (ABCA1), within actin filament associated protein 1 (AFAP1) and within GDP-mannose 46-dehydratase (GMDS). (PMID:25173105)
• Disruptions of enhancers near FOXC1 and GMDS may influence brain development. (PMID:26382291)
• Study findings suggest that GMDS upregulation is critical for cell proliferation and survival in human lung adenocarcinoma and might serve as a potential biomarker for lung adenocarcinoma diagnosis and treatment. (PMID:29843634)
• we present an analysis of the sequence and structural features governing TNKS interactions with two model binding partners: the PARylated partner telomeric repeat-binding factor 1 (TRF1) and the non-PARylated partner GDP-mannose 4,6-dehydratase (GMD). (PMID:31375564)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	gmds	ENSDARG00000026629
mus_musculus	Gmds	ENSMUSG00000038372
rattus_norvegicus	Gmds	ENSRNOG00000017605
drosophila_melanogaster	Gmd	FBGN0031661
caenorhabditis_elegans		WBGENE00000266
caenorhabditis_elegans	gmd-2	WBGENE00010166

Paralogs (10): TGDS (ENSG00000088451), HSD3B7 (ENSG00000099377), GFUS (ENSG00000104522), UXS1 (ENSG00000115652), GALE (ENSG00000117308), NSDHL (ENSG00000147383), SDR42E2 (ENSG00000183921), SDR42E1 (ENSG00000184860), HSD3B1 (ENSG00000203857), HSD3B2 (ENSG00000203859)

Protein

Protein identifiers

GDP-mannose 4,6 dehydratase — O60547 (reviewed: O60547)

Alternative names: GDP-D-mannose dehydratase

All UniProt accessions (1): O60547

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the conversion of GDP-D-mannose to GDP-4-dehydro-6-deoxy-D-mannose.

Tissue specificity. Highly expressed in pancreas and small intestine. Expressed in thymus, protstate, colon, heart, placenta, liver and kidney. Expressed at low levels in spleen, testis, brain and lung.

Activity regulation. Inhibited by GDP-fucose.

Pathway. Nucleotide-sugar biosynthesis; GDP-L-fucose biosynthesis via de novo pathway; GDP-L-fucose from GDP-alpha-D-mannose: step 1/2.

Similarity. Belongs to the NAD(P)-dependent epimerase/dehydratase family. GDP-mannose 4,6-dehydratase subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
O60547-1	1	yes
O60547-2	2

RefSeq proteins (2): NP_001240775, NP_001491* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006368	GDP_Man_deHydtase	Family
IPR016040	NAD(P)-bd_dom	Domain
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily

Pfam: PF16363

Enzyme classification (BRENDA):

• EC 4.2.1.47 — GDP-mannose 4,6-dehydratase (BRENDA: 26 organisms, 19 substrates, 33 inhibitors, 19 Km, 11 kcat entries)

Substrate kinetics (BRENDA)

3 substrates with measured Km, best-characterized 3. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
GDP-MANNOSE	0.0035–1.02	9
GDPMANNOSE	0.003–0.55	7
GDP-ALPHA-D-MANNOSE	0.008–1.024	3

Catalyzed reactions (Rhea), 1 shown:

• GDP-alpha-D-mannose = GDP-4-dehydro-alpha-D-rhamnose + H2O (RHEA:23820)

UniProt features (55 total): strand 16, helix 15, binding site 8, turn 6, active site 3, modified residue 2, initiator methionine 1, chain 1, splice variant 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
6GPK	X-RAY DIFFRACTION	1.47
5IN4	X-RAY DIFFRACTION	1.6
6GPL	X-RAY DIFFRACTION	1.76
1T2A	X-RAY DIFFRACTION	1.84
5IN5	X-RAY DIFFRACTION	1.9
6GPJ	X-RAY DIFFRACTION	1.94
6Q94	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60547-F1	94.59	0.91

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 155; 157 (nucleophile); 179 (nucleophile)

Ligand- & substrate-binding residues (8): 123; 183; 209; 214; 30–35; 55–58; 86–87; 108–112

Post-translational modifications (2): 2, 323

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6787639	GDP-fucose biosynthesis

MSigDB gene sets: 173 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, chr6p25, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, WTGAAAT_UNKNOWN, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, GOMF_HYDRO_LYASE_ACTIVITY, CUI_TCF21_TARGETS_2_DN, DANG_BOUND_BY_MYC, IZADPANAH_STEM_CELL_ADIPOSE_VS_BONE_UP

GO Biological Process (4): Notch signaling pathway (GO:0007219), GDP-mannose metabolic process (GO:0019673), GDP-L-fucose biosynthetic process (GO:0042350), ‘de novo’ GDP-L-fucose biosynthetic process (GO:0042351)

GO Molecular Function (5): GDP-mannose 4,6-dehydratase activity (GO:0008446), identical protein binding (GO:0042802), NADP+ binding (GO:0070401), protein binding (GO:0005515), lyase activity (GO:0016829)

GO Cellular Component (3): cytoplasm (GO:0005737), cytosol (GO:0005829), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Synthesis of substrates in N-glycan biosythesis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cell surface receptor signaling pathway	1
nucleotide-sugar metabolic process	1
nucleotide-sugar biosynthetic process	1
GDP-L-fucose metabolic process	1
GDP-mannose metabolic process	1
GDP-L-fucose biosynthetic process	1
hydro-lyase activity	1
protein binding	1
anion binding	1
NADP binding	1
binding	1
catalytic activity	1
intracellular anatomical structure	1
cytoplasm	1
extracellular vesicle	1

Protein interactions and networks

STRING

1312 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GMDS	FOXC1	Q12948	886
GMDS	SLC35C1	Q96A29	801
GMDS	FOXF2	Q12947	779
GMDS	GFUS	Q13630	771
GMDS	FOXQ1	Q9C009	770
GMDS	FCSK	Q8N0W3	729
GMDS	FPGT	O14772	715
GMDS	FUT8	Q9BYC5	691
GMDS	AFAP1	Q8N556	660
GMDS	FUT1	P19526	618
GMDS	TMCO1	Q9UM00	609
GMDS	GALE	Q14376	608
GMDS	GAS7	O60861	603
GMDS	UGDH	O60701	589
GMDS	CYP1B1	Q16678	575

IntAct

47 interactions, top by confidence:

A	B	Type	Score
GMDS	GMDS	psi-mi:“MI:0915”(physical association)	0.800
GMDS	NTAQ1	psi-mi:“MI:0915”(physical association)	0.720
NTAQ1	GMDS	psi-mi:“MI:0915”(physical association)	0.720
HIF1AN	GMDS	psi-mi:“MI:0914”(association)	0.640
GMDS	TAE1	psi-mi:“MI:0915”(physical association)	0.560
TAE1	GMDS	psi-mi:“MI:0915”(physical association)	0.560
KCNAB3	GMDS	psi-mi:“MI:0915”(physical association)	0.560
GMDS	TNKS	psi-mi:“MI:0914”(association)	0.530
	GMDS	psi-mi:“MI:0915”(physical association)	0.400
Shoc2	GABPB1	psi-mi:“MI:0914”(association)	0.350
SKA1	ILVBL	psi-mi:“MI:0914”(association)	0.350
Rab5c		psi-mi:“MI:0914”(association)	0.350
Tnks	SDC2	psi-mi:“MI:0914”(association)	0.350
Tnks2	AMOTL2	psi-mi:“MI:0914”(association)	0.350
Smad3	GMDS	psi-mi:“MI:0914”(association)	0.350
Ddb1		psi-mi:“MI:0914”(association)	0.350
Kif2a	GMDS	psi-mi:“MI:0914”(association)	0.350
CCDC22	VPS26C	psi-mi:“MI:0914”(association)	0.350
HIF1AN	CNOT1	psi-mi:“MI:0914”(association)	0.350
ORF17.5	WWP2	psi-mi:“MI:0914”(association)	0.350
PB2		psi-mi:“MI:0914”(association)	0.350

BioGRID (91): GMDS (Two-hybrid), WDYHV1 (Two-hybrid), GMDS (Affinity Capture-MS), GMDS (Two-hybrid), GMDS (Co-fractionation), GMDS (Co-fractionation), GMDS (Co-fractionation), NDUFA9 (Co-fractionation), PSMG4 (Co-fractionation), GMDS (Affinity Capture-MS), GMDS (Affinity Capture-MS), GMDS (Affinity Capture-MS), GMDS (Affinity Capture-MS), GMDS (Affinity Capture-MS), GMDS (Affinity Capture-MS)

ESM2 similar proteins: A6QLW2, A8Y0L5, B0M3E8, O43050, O45583, O60547, O64749, O65780, O65781, O95455, P04397, P21977, P26391, P39630, P55293, P55462, P93031, P95780, P96995, Q04973, Q06952, Q18801, Q42605, Q43070, Q55C77, Q564Q1, Q5UR12, Q652A8, Q6E7F4, Q7BJX9, Q8H0B2, Q8H0B6, Q8K0C9, Q8K3X3, Q8LDN8, Q8LNZ3, Q8VDR7, Q9C7W7, Q9LH76, Q9LPG6

Diamond homologs: A0A1B4XBH2, A8Y0L5, O45583, O60547, O85713, P0AC88, P0AC89, P0AC90, P0AC91, P35675, P55354, P73212, P93031, Q06952, Q18801, Q1ZXF7, Q51366, Q56598, Q56872, Q8K0C9, Q8K3X3, Q9JRN5, Q9SNY3, Q9VMW9, A0QSK6, B9J8R3, Q6T1X6, Q0D1P7, P9WN64, P9WN65, A0R5C5, P39630, P9WN66, P9WN67, P26397, O06485, O81312, Q9STI6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

73 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	55
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1527212	GRCh37/hg19 6p25.3-25.2(chr6:383951-3898619)	Pathogenic
443604	GRCh37/hg19 6p25.3(chr6:1703078-1918006)x1	Likely pathogenic

SpliceAI

6776 predictions. Top by Δscore:

Variant	Effect	Δscore
6:1624230:TCCTG:T	acceptor_loss	1.0000
6:1624231:CCTGC:C	acceptor_loss	1.0000
6:1624468:TCACA:T	donor_loss	1.0000
6:1624469:CA:C	donor_loss	1.0000
6:1624470:A:AC	donor_gain	1.0000
6:1624470:ACAT:A	donor_gain	1.0000
6:1624471:C:CT	donor_gain	1.0000
6:1624471:CA:C	donor_gain	1.0000
6:1624471:CAT:C	donor_gain	1.0000
6:1624471:CATC:C	donor_gain	1.0000
6:1624471:CATCG:C	donor_gain	1.0000
6:1726411:CTTA:C	donor_loss	1.0000
6:1726414:A:T	donor_loss	1.0000
6:1726415:C:A	donor_loss	1.0000
6:1726415:CCA:C	donor_gain	1.0000
6:1726508:CCCAC:C	acceptor_gain	1.0000
6:1726509:CCAC:C	acceptor_gain	1.0000
6:1726509:CCACC:C	acceptor_gain	1.0000
6:1726510:CAC:C	acceptor_gain	1.0000
6:1726510:CACC:C	acceptor_gain	1.0000
6:1726511:ACCT:A	acceptor_loss	1.0000
6:1726513:C:G	acceptor_loss	1.0000
6:1726514:T:A	acceptor_loss	1.0000
6:1742461:TACT:T	donor_loss	1.0000
6:1742462:ACTTA:A	donor_loss	1.0000
6:1742463:CTTAC:C	donor_loss	1.0000
6:1742464:TT:T	donor_loss	1.0000
6:1742465:TAC:T	donor_gain	1.0000
6:1742466:A:AC	donor_gain	1.0000
6:1742466:A:T	donor_loss	1.0000

AlphaMissense

2441 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:1930129:A:G	W249R	1.000
6:1930129:A:T	W249R	1.000
6:1930220:G:C	F218L	1.000
6:1930220:G:T	F218L	1.000
6:1930222:A:G	F218L	1.000
6:1959886:A:C	N208K	1.000
6:1959886:A:T	N208K	1.000
6:1726511:A:G	W298R	0.999
6:1726511:A:T	W298R	0.999
6:1930127:C:A	W249C	0.999
6:1930127:C:G	W249C	0.999
6:1930202:G:C	S224R	0.999
6:1930202:G:T	S224R	0.999
6:1930204:T:G	S224R	0.999
6:1930218:A:T	V219D	0.999
6:1930221:A:C	F218C	0.999
6:1930221:A:G	F218S	0.999
6:1959869:C:G	R214T	0.999
6:1959877:A:C	S211R	0.999
6:1959877:A:T	S211R	0.999
6:1959879:T:G	S211R	0.999
6:1959885:G:C	H209D	0.999
6:1959889:G:C	F207L	0.999
6:1959889:G:T	F207L	0.999
6:1959891:A:G	F207L	0.999
6:1959899:C:T	G204D	0.999
6:1959929:C:G	R194P	0.999
6:1960774:C:A	G180W	0.999
6:1960844:A:C	S156R	0.999
6:1960844:A:T	S156R	0.999

dbSNP variants (sampled 300 via entrez): RS1000006294 (6:1684746 C>T), RS1000008262 (6:1879429 C>G), RS1000009650 (6:2084195 T>C), RS1000010055 (6:1684466 G>A), RS1000011837 (6:1841322 T>C), RS1000020145 (6:1853275 T>C), RS1000025575 (6:1964112 C>T), RS1000025912 (6:1756760 C>G), RS1000029967 (6:1689583 C>T), RS1000033165 (6:1766857 G>A), RS1000044855 (6:1853582 G>GTGTA), RS1000053980 (6:1697346 T>C), RS1000058795 (6:2039920 T>C,G), RS1000059087 (6:1957724 T>A,C), RS1000065072 (6:1879056 G>T)

Disease associations

OMIM: gene MIM:602884 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): intellectual disability (MONDO:0001071)

Orphanet (1): NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

62 associations (top):

Study	Trait	p-value
GCST001045_1	Caudate nucleus volume	6.000000e-06
GCST001291_3	Response to platinum-based agents	5.000000e-06
GCST001762_801	Obesity-related traits	9.000000e-06
GCST002582_3	Glaucoma (primary open-angle)	8.000000e-10
GCST003251_15	Late-onset myasthenia gravis	2.000000e-06
GCST003477_1	Monobrow thickness	2.000000e-06
GCST003518_54	Daytime sleep phenotypes	4.000000e-08
GCST003518_74	Daytime sleep phenotypes	2.000000e-06
GCST003518_8	Daytime sleep phenotypes	1.000000e-06
GCST003996_49	Monobrow	4.000000e-13
GCST004067_52	Hip circumference adjusted for BMI	9.000000e-09
GCST004601_67	Red blood cell count	6.000000e-19
GCST004604_101	Hematocrit	1.000000e-17
GCST004615_26	Hemoglobin concentration	7.000000e-15
GCST005194_217	Coronary artery disease	4.000000e-08
GCST005196_90	Coronary artery disease	2.000000e-08
GCST005580_13	Intraocular pressure	7.000000e-15
GCST005580_237	Intraocular pressure	7.000000e-17
GCST006065_15	Glaucoma (primary open-angle)	2.000000e-10
GCST006394_4	Intraocular pressure	2.000000e-12
GCST006394_5	Intraocular pressure	2.000000e-17
GCST006412_52	Intraocular pressure	1.000000e-13
GCST006412_53	Intraocular pressure	1.000000e-21
GCST006412_54	Intraocular pressure	3.000000e-19
GCST006979_486	Heel bone mineral density	7.000000e-18
GCST007269_261	Pulse pressure	2.000000e-11
GCST007490_11	Anthropometric traits (multi-trait analysis)	2.000000e-10
GCST007629_4	Impulsivity (non-planning)	1.000000e-06
GCST007742_11	Iris heterochromicity	6.000000e-06
GCST007928_35	Medication use (diuretics)	4.000000e-08

EFO canonical traits (21, from GWAS)

EFO ID	Trait name
EFO:0004908	testosterone measurement
EFO:0007828	daytime rest measurement
EFO:0007906	synophrys measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0004305	erythrocyte count
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0004695	intraocular pressure measurement
EFO:0009270	heel bone mineral density
EFO:0005763	pulse pressure measurement
EFO:0004324	body weights and measures
EFO:0006946	behavioural disinhibition measurement
EFO:0009764	eye colour measurement
EFO:0009928	Diuretic use measurement
EFO:0010139	fish consumption measurement
EFO:0004531	urate measurement
EFO:0005420	grey matter volume measurement
EFO:0006939	cup-to-disc ratio measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0007986	reticulocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105807 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

1 potent at pChembl≥5 of 4 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.00	IC50	1e+04	nM	MOLIBRESIB

PubChem BioAssay actives

1 with measured affinity, of 12 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178927: Inhibition of GMDS (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	10.0000	uM

CTD chemical–gene interactions

55 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	8
Valproic Acid	affects cotreatment, increases expression, affects expression	7
Aflatoxin B1	affects methylation, decreases expression, increases methylation, affects expression	6
bisphenol A	decreases expression, increases expression, affects cotreatment, decreases methylation	3
Cisplatin	affects cotreatment, decreases expression	3
Acetaminophen	decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
aristolochic acid I	decreases expression	1
methyleugenol	decreases expression	1
sulforaphane	decreases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
ochratoxin A	increases expression	1
benzo(e)pyrene	affects methylation	1
aflatoxin B2	increases methylation	1
beta-methylcholine	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
candoxin	decreases expression	1
ICG 001	increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
enzalutamide	affects expression	1
bisphenol S	decreases methylation	1
jinfukang	affects cotreatment, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	increases expression	1
Decitabine	decreases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4012908	Binding	Binding affinity to GMDS in human Jurkat cell extract up to 5 uM after 1 hr using NHS-activated sepharose coupled Piperazin-1-yl(4-(tetrazolo[1,5-a]quinoxalin-4-ylamino)phenyl)-methanone by mass spectrometry based chemoproteomic assay	Discovery of a Highly Selective Tankyrase Inhibitor Displaying Growth Inhibition Effects against a Diverse Range of Tumor Derived Cell Lines. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SQ12	HAP1 GMDS (-)	Cancer cell line	Male

Clinical trials (associated diseases)

197 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders