GPD2

Summary

GPD2 (glycerol-3-phosphate dehydrogenase 2, HGNC:4456) is a protein-coding gene on chromosome 2q24.1, encoding Glycerol-3-phosphate dehydrogenase, mitochondrial (P43304). Calcium-responsive mitochondrial glycerol-3-phosphate dehydrogenase which seems to be a key component of the pancreatic beta-cell glucose-sensing device.

The protein encoded by this gene localizes to the inner mitochondrial membrane and catalyzes the conversion of glycerol-3-phosphate to dihydroxyacetone phosphate, using FAD as a cofactor. Along with GDP1, the encoded protein constitutes the glycerol phosphate shuttle, which reoxidizes NADH formed during glycolysis. Two transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 2820 — RefSeq curated summary.

At a glance

• Gene–disease (curated): diabetes mellitus, noninsulin-dependent (No Known Disease Relationship, GenCC)
• GWAS associations: 18
• Clinical variants (ClinVar): 129 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 5
• Druggable target: yes
• MANE Select transcript: NM_000408

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4456
Approved symbol	GPD2
Name	glycerol-3-phosphate dehydrogenase 2
Location	2q24.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000115159
Ensembl biotype	protein_coding
OMIM	138430
Entrez	2820

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 14 protein_coding, 4 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000310454, ENST00000409674, ENST00000409861, ENST00000415049, ENST00000416888, ENST00000430992, ENST00000438166, ENST00000464846, ENST00000492005, ENST00000495851, ENST00000496190, ENST00000540309, ENST00000893602, ENST00000893603, ENST00000893604, ENST00000893605, ENST00000893606, ENST00000893607, ENST00000893608, ENST00000893609, ENST00000893610, ENST00000893611

RefSeq mRNA: 2 — MANE Select: NM_000408 NM_000408, NM_001083112

CCDS: CCDS2202

Canonical transcript exons

ENST00000438166 — 17 exons

Exon	Start	End
ENSE00000778506	156510796	156510920
ENSE00001188495	156582793	156586403
ENSE00001581432	156436379	156436513
ENSE00001596519	156513333	156513496
ENSE00001655975	156550602	156550746
ENSE00001667537	156512220	156512317
ENSE00001669783	156568825	156568959
ENSE00001685130	156570087	156570218
ENSE00001689131	156557389	156557582
ENSE00001748838	156569363	156569538
ENSE00001768130	156578889	156579001
ENSE00001784164	156571134	156571292
ENSE00003488102	156579086	156579164
ENSE00003546640	156496044	156496215
ENSE00003554397	156579690	156579788
ENSE00003688248	156476098	156476207
ENSE00003745755	156549608	156549772

Expression profiles

Bgee: expression breadth ubiquitous, 271 present calls, max score 97.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.7097 / max 312.3710, expressed in 1758 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
23174	11.0671	1684
23173	2.6390	1084
23175	1.7138	988
23169	0.5606	268
23171	0.4588	249
23168	0.3789	206
23170	0.3123	149
23172	0.2801	156
23176	0.2764	135
23177	0.0227	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	97.66	gold quality
sperm	CL:0000019	96.21	gold quality
oocyte	CL:0000023	95.25	gold quality
esophagus squamous epithelium	UBERON:0006920	94.81	gold quality
buccal mucosa cell	CL:0002336	93.90	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.51	gold quality
jejunal mucosa	UBERON:0000399	93.42	gold quality
colonic mucosa	UBERON:0000317	93.10	gold quality
male germ cell	CL:0000015	92.71	gold quality
calcaneal tendon	UBERON:0003701	92.58	gold quality
gingival epithelium	UBERON:0001949	92.44	gold quality
cortical plate	UBERON:0005343	92.09	gold quality
oral cavity	UBERON:0000167	91.80	gold quality
gingiva	UBERON:0001828	91.63	gold quality
ventricular zone	UBERON:0003053	91.40	gold quality
ganglionic eminence	UBERON:0004023	91.12	gold quality
epithelium of nasopharynx	UBERON:0001951	90.94	gold quality
rectum	UBERON:0001052	90.26	gold quality
mucosa of paranasal sinus	UBERON:0005030	90.19	gold quality
biceps brachii	UBERON:0001507	89.69	gold quality
upper leg skin	UBERON:0004262	89.33	gold quality
tendon	UBERON:0000043	89.25	gold quality
palpebral conjunctiva	UBERON:0001812	89.01	gold quality
jejunum	UBERON:0002115	88.91	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	88.69	gold quality
islet of Langerhans	UBERON:0000006	88.66	gold quality
esophagus mucosa	UBERON:0002469	88.61	gold quality
epithelium of esophagus	UBERON:0001976	88.23	gold quality
tonsil	UBERON:0002372	88.13	gold quality
monocyte	CL:0000576	87.91	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	260.58
E-ANND-3	yes	7.01

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXO1

miRNA regulators (miRDB)

220 targeting GPD2, 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-4262	100.00	73.26	3931
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-495-3P	99.96	72.81	4197

Literature-anchored findings (GeneRIF, showing 11)

• testis-specific promoter of mitochondrial GPDH (PMID:15456763)
• Overall, these data demonstrate that mGPDH is involved in maintaining a high rate of glycolysis and is an important site of electron leakage leading to ROS production in prostate cancer cells. (PMID:15967408)
• the up-regulation of mGPDH, due to a highly glycolytic environment, contributes to the overall increase in ROS generation and may result in the progression of prostate cancer (PMID:17886033)
• We report 3 additional patients with a de novo deletion encompassing NR4A2: 2 patients have deletions encompassing only NR4A2 gene and 1 patient has a deletion including NR4A2 and the first exon of GPD2 (PMID:29770430)
• Here, the authors identify mGPDH as a critical regulator of skeletal muscle regeneration. Specifically, it regulates myogenic markers and myoblast differentiation by controlling mitochondrial biogenesis via CaMKKbeta/AMPK. (PMID:30389681)
• mRNA and protein levels reduced in livers of patients with nonalcoholic fatty liver disease (PMID:30653687)
• Deficiency of Mitochondrial Glycerol 3-Phosphate Dehydrogenase Exacerbates Podocyte Injury and the Progression of Diabetic Kidney Disease. (PMID:33741719)
• mGPDH Deficiency leads to melanoma metastasis via induced NRF2. (PMID:33939274)
• A ferroptosis defense mechanism mediated by glycerol-3-phosphate dehydrogenase 2 in mitochondria. (PMID:35749365)
• GPD2: The relationship with cancer and neural stemness. (PMID:36592694)
• Glycerol 3-phosphate dehydrogenases (1 and 2) in cancer and other diseases. (PMID:38689091)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpd2	ENSDARG00000062430
mus_musculus	Gpd2	ENSMUSG00000026827
rattus_norvegicus	Gpd2	ENSRNOG00000033824
drosophila_melanogaster	Gpo1	FBGN0022160
drosophila_melanogaster	Gpo3	FBGN0028848
drosophila_melanogaster	Gpo2	FBGN0033190
caenorhabditis_elegans	gpdh-3	WBGENE00012031
caenorhabditis_elegans		WBGENE00013049

Protein

Protein identifiers

Glycerol-3-phosphate dehydrogenase, mitochondrial — P43304 (reviewed: P43304)

Alternative names: mitochondrial glycerophosphate dehydrogenase gene, mtGPD

All UniProt accessions (4): P43304, E7EM56, E9PDK4, F5GYK7

UniProt curated annotations — full annotation on UniProt →

Function. Calcium-responsive mitochondrial glycerol-3-phosphate dehydrogenase which seems to be a key component of the pancreatic beta-cell glucose-sensing device.

Subcellular location. Mitochondrion.

Activity regulation. Calcium-binding enhance the activity of the enzyme.

Pathway. Polyol metabolism; glycerol degradation via glycerol kinase pathway; glycerone phosphate from sn-glycerol 3-phosphate (anaerobic route): step 1/1.

Similarity. Belongs to the FAD-dependent glycerol-3-phosphate dehydrogenase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P43304-1	1	yes
P43304-2	2

RefSeq proteins (2): NP_000399, NP_001076581 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000447	G3P_DH_FAD-dep	Family
IPR002048	EF_hand_dom	Domain
IPR006076	FAD-dep_OxRdtase	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR018247	EF_Hand_1_Ca_BS	Binding_site
IPR031656	DAO_C	Domain
IPR036188	FAD/NAD-bd_sf	Homologous_superfamily
IPR038299	DAO_C_sf	Homologous_superfamily

Pfam: PF01266, PF13499, PF16901

Enzyme classification (BRENDA):

• EC 1.1.5.3 — glycerol-3-phosphate dehydrogenase (BRENDA: 17 organisms, 47 substrates, 82 inhibitors, 25 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

12 substrates with measured Km, best-characterized 12. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
GLYCEROL 3-PHOSPHATE	0.1–3.2	5
SN-GLYCEROL 3-PHOSPHATE	3.7–10	4
DL-GLYCEROL 3-PHOSPHATE	0.8–10.2	3
2,6-DICHLOROPHENOLINDOPHENOL	0.076–0.125	2
COENZYME Q1	0.013–0.052	2
COENZYME Q0	0.125	1
COENZYME Q10	0.05	1
COENZYME Q2	0.023	1
COENZYME Q6	0.11	1
DL-ALPHA-GLYCEROPHOSPHATE	5.17	1
FERRICYANIDE	0.55	1
PHENAZINE METHOSULFATE	0.13	1

Catalyzed reactions (Rhea), 1 shown:

• a quinone + sn-glycerol 3-phosphate = dihydroxyacetone phosphate + a quinol (RHEA:18977)

UniProt features (18 total): sequence variant 6, binding site 6, domain 2, transit peptide 1, chain 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P43304-F1	86.47	0.60

Functional residue map

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

Ligand- & substrate-binding residues (6): 71–99; 672; 674; 676; 678; 683

Post-translational modifications (1): 601

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-1483166	Synthesis of PA
R-HSA-163560	Triglyceride catabolism

MSigDB gene sets: 339 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, REACTOME_TRIGLYCERIDE_CATABOLISM, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_POLYOL_METABOLIC_PROCESS, GOBP_GROWTH, GOBP_POLYOL_CATABOLIC_PROCESS, KYNG_DNA_DAMAGE_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, BROWNE_HCMV_INFECTION_12HR_UP, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NADPLUS_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, MODULE_205

GO Biological Process (7): glycerol-3-phosphate metabolic process (GO:0006072), gluconeogenesis (GO:0006094), glycerol-3-phosphate shuttle (GO:0006127), glycerol catabolic process (GO:0019563), multicellular organism growth (GO:0035264), camera-type eye development (GO:0043010), obsolete NADH metabolic process (GO:0006734)

GO Molecular Function (5): glycerol-3-phosphate dehydrogenase (quinone) activity (GO:0004368), calcium ion binding (GO:0005509), glycerol-3-phosphate dehydrogenase [NAD(P)+] activity (GO:0047952), oxidoreductase activity (GO:0016491), metal ion binding (GO:0046872)

GO Cellular Component (2): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Glycerophospholipid biosynthesis	1
Triglyceride metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
alditol phosphate metabolic process	1
glucose metabolic process	1
hexose biosynthetic process	1
glycerol-3-phosphate dehydrogenase (quinone) activity	1
NAD+ metabolic process	1
glycerol-3-phosphate dehydrogenase (NAD+) activity	1
glycerol metabolic process	1
alditol catabolic process	1
multicellular organismal process	1
developmental growth	1
eye development	1
oxidoreductase activity, acting on the CH-OH group of donors, quinone or similar compound as acceptor	1
metal ion binding	1
oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	1
catalytic activity	1
cation binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1

Protein interactions and networks

STRING

2234 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPD2	GPD1	P21695	980
GPD2	PC	P11498	776
GPD2	ACACA	Q13085	562
GPD2	MDH2	P40926	545
GPD2	GAPDH	P00354	537
GPD2	GK2	Q14410	517
GPD2	SLC2A2	P11168	508
GPD2	GLUD1	P00367	504
GPD2	GPAM	Q9HCL2	503
GPD2	PFKM	P08237	499
GPD2	GK	P32189	496
GPD2	GABPA	Q06546	493
GPD2	MICOS10	Q5TGZ0	480
GPD2	TPI1	P00938	478
GPD2	SDHA	P31040	478

IntAct

86 interactions, top by confidence:

A	B	Type	Score
ASPH	STXBP3	psi-mi:“MI:0914”(association)	0.640
GPD2		psi-mi:“MI:0915”(physical association)	0.550
SLC39A4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
GDPD5	GOLIM4	psi-mi:“MI:0914”(association)	0.530
CD63	LGALS8	psi-mi:“MI:0914”(association)	0.530
ATP1A3	AGPAT2	psi-mi:“MI:0914”(association)	0.530
DUSP29	PDHB	psi-mi:“MI:0914”(association)	0.420
	ESYT2	psi-mi:“MI:0914”(association)	0.350
PB2		psi-mi:“MI:0914”(association)	0.350
OAS3	PTBP1	psi-mi:“MI:0914”(association)	0.350
APOOL	MGST3	psi-mi:“MI:0914”(association)	0.350
COQ9	NDUFS8	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
COQ8A	ESYT2	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
CRELD1	TMEM223	psi-mi:“MI:0914”(association)	0.350
RAMP2	GXYLT2	psi-mi:“MI:0914”(association)	0.350
ATP2A1	TMEM120B	psi-mi:“MI:0914”(association)	0.350
TSPAN10	KLRG2	psi-mi:“MI:0914”(association)	0.350
AQP3	RTL8C	psi-mi:“MI:0914”(association)	0.350
CMTM8	UBXN8	psi-mi:“MI:0914”(association)	0.350
SLC18A2	UBXN8	psi-mi:“MI:0914”(association)	0.350
PVR	QSOX1	psi-mi:“MI:0914”(association)	0.350
HAX1	DNM1L	psi-mi:“MI:0914”(association)	0.350
MDFI	GOLIM4	psi-mi:“MI:0914”(association)	0.350
SLC39A8	GOLIM4	psi-mi:“MI:0914”(association)	0.350

BioGRID (153): GPD2 (Affinity Capture-MS), GPD2 (Affinity Capture-MS), GPD2 (Affinity Capture-MS), GPD2 (Affinity Capture-MS), GPD2 (Affinity Capture-MS), GPD2 (Affinity Capture-MS), GPD2 (Affinity Capture-MS), GPD2 (Affinity Capture-MS), GPD2 (Co-fractionation), GPD2 (Co-fractionation), GPD2 (Co-fractionation), COX2 (Co-fractionation), GPD2 (Affinity Capture-MS), GPD2 (Affinity Capture-MS), GPD2 (Affinity Capture-MS)

ESM2 similar proteins: A0A084R1J7, A0A097ZPG2, A0A0F7TXA5, A0A0F7TXA8, A0A0L1JEZ9, A0A0U4ZPL6, A0A0U5HAQ4, A0A142I725, A0A1E1FFN4, A0A1E1FFN7, A0A1L9WQQ1, A0A2I1BSU0, A0A2I2F2Q7, A0A2U8U2L6, A0A3G9K5C8, A0A443HK11, A0A516F3Z6, A1CLY7, A2QK68, A6QLU1, A8MRX0, A8NF99, B1GVX4, B2KWI1, B8NM63, C8VE79, D2E9W9, G2QA95, G5EB76, I1RF61, I1RN13, M2Y0N8, N4WYI1, O14121, P0DXV5, P0DXV6, P43304, P55487, P90795, Q00730

Diamond homologs: A2WN93, A2WNH1, A2Y609, A3E3H0, A3E4D8, A3E4F9, A4UHC0, A6QLU1, A7DZP8, A8I1Q0, O14400, O23320, O60041, O82018, O86963, P02598, P02599, P04353, P04464, P06708, P06787, P0DB20, P0DB21, P0DH95, P0DH96, P0DH97, P0DH98, P13035, P17928, P18158, P21797, P23286, P27164, P27166, P32191, P35571, P35596, P41041, P43304, P53435

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 113 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
R-HSA-425366	7	16.7×	5e-05
SLC-mediated transmembrane transport	8	6.2×	2e-03
Transport of small molecules	13	4.3×	8e-04

GO biological processes:

GO term	Partners	Fold	FDR
amino acid transport	6	18.4×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	93
Likely benign	8
Benign	1

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
16081	NM_000408.5(GPD2):c.1904T>C (p.Phe635Ser)	Pathogenic
1807710	GRCh37/hg19 2q24.1(chr2:156996368-157372032)x1	Likely pathogenic

SpliceAI

3108 predictions. Top by Δscore:

Variant	Effect	Δscore
2:156476084:A:AG	acceptor_gain	1.0000
2:156476085:T:G	acceptor_gain	1.0000
2:156476095:TA:T	acceptor_loss	1.0000
2:156476096:A:AG	acceptor_gain	1.0000
2:156476096:A:T	acceptor_loss	1.0000
2:156476096:AG:A	acceptor_gain	1.0000
2:156476097:G:GC	acceptor_gain	1.0000
2:156476097:GG:G	acceptor_gain	1.0000
2:156476097:GGC:G	acceptor_gain	1.0000
2:156476097:GGCT:G	acceptor_gain	1.0000
2:156476097:GGCTA:G	acceptor_gain	1.0000
2:156476203:AACAA:A	donor_gain	1.0000
2:156476204:ACAA:A	donor_gain	1.0000
2:156476205:CAA:C	donor_gain	1.0000
2:156476205:CAAG:C	donor_loss	1.0000
2:156476206:AA:A	donor_gain	1.0000
2:156476206:AAG:A	donor_loss	1.0000
2:156476208:G:GG	donor_gain	1.0000
2:156476209:TA:T	donor_loss	1.0000
2:156476210:AA:A	donor_loss	1.0000
2:156510785:T:A	acceptor_gain	1.0000
2:156510792:ACAG:A	acceptor_gain	1.0000
2:156510793:C:G	acceptor_gain	1.0000
2:156510793:CA:C	acceptor_loss	1.0000
2:156510794:A:AG	acceptor_gain	1.0000
2:156510794:AG:A	acceptor_gain	1.0000
2:156510795:G:GA	acceptor_gain	1.0000
2:156510795:GG:G	acceptor_gain	1.0000
2:156510795:GGA:G	acceptor_gain	1.0000
2:156510795:GGACT:G	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000011054 (2:156534366 A>G), RS1000026982 (2:156438265 A>G), RS1000039721 (2:156479196 T>C), RS1000042069 (2:156518915 T>C), RS1000068700 (2:156584660 C>A,G,T), RS1000080077 (2:156480335 G>A), RS1000089410 (2:156575578 A>AT), RS1000106623 (2:156474886 TAGG>T), RS1000118489 (2:156576225 C>A,T), RS1000134193 (2:156418834 T>A), RS1000148519 (2:156424567 A>G), RS1000167641 (2:156528513 G>C), RS1000176392 (2:156413342 G>A), RS1000188264 (2:156567880 T>C), RS1000211539 (2:156424214 A>C)

Disease associations

OMIM: gene MIM:138430 | disease phenotypes: MIM:125853

GenCC curated gene-disease

Disease	Classification	Inheritance
diabetes mellitus, noninsulin-dependent	No Known Disease Relationship	Autosomal dominant

Mondo (2): type 2 diabetes mellitus (MONDO:0005148), (MONDO:0007455)

Orphanet (0):

HPO phenotypes

5 total (5 of 5 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000855	Insulin resistance
HP:0003584	Late onset
HP:0005978	Type II diabetes mellitus
HP:0031819	Increased waist to hip ratio

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST000635_3	Response to statin therapy	9.000000e-06
GCST002548_3	Ulcerative colitis	6.000000e-06
GCST002759_2	Motion sickness	2.000000e-29
GCST002875_45	Diisocyanate-induced asthma	1.000000e-06
GCST003963_3	Possible neuropathic pain in post total joint replacement surgery for osteoarthritis	3.000000e-06
GCST003997_10	Myopia	6.000000e-13
GCST005141_81	Cognitive ability (MTAG)	1.000000e-09
GCST005142_3	Cognitive ability	4.000000e-09
GCST005316_153	Intelligence (MTAG)	4.000000e-08
GCST005316_154	Intelligence (MTAG)	8.000000e-13
GCST005316_155	Intelligence (MTAG)	7.000000e-10
GCST005316_156	Intelligence (MTAG)	3.000000e-08
GCST005839_7	Depression	2.000000e-08
GCST006088_22	Familial squamous cell lung carcinoma	3.000000e-06
GCST006269_1218	General cognitive ability	4.000000e-08
GCST006291_120	Spherical equivalent or myopia (age of diagnosis)	5.000000e-15
GCST009640_11	Urinary albumin-to-creatinine ratio	1.000000e-08
GCST010002_401	Refractive error	1.000000e-35

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0006928	motion sickness
EFO:0006995	response to diisocyanate
EFO:0005762	neuropathic pain
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0006953	family history of lung cancer
EFO:0004847	age at onset
EFO:0007778	urinary albumin to creatinine ratio

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D003924	Diabetes Mellitus, Type 2	C18.452.394.750.149; C19.246.300

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3391681 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases methylation	6
sodium arsenite	decreases expression, increases expression	2
Benzo(a)pyrene	affects methylation, increases expression	2
Aflatoxin B1	affects expression, decreases methylation	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
pyrogallol 1,3-dimethyl ether	increases expression, affects cotreatment	1
trichostatin A	affects expression	1
beta-lapachone	decreases expression	1
cobaltous chloride	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression, increases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic Trioxide	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Troglitazone	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arbutin	increases expression	1
Arsenic	affects methylation	1
Clozapine	decreases expression	1
Coal	decreases expression, increases abundance	1
Coumestrol	increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1FG	Abcam A-431 GPD2 KO	Cancer cell line	Female
CVCL_E1YD	HAP1 GPD2 (-) 2	Cancer cell line	Male
CVCL_E1YE	HAP1 GPD2 (-) 3	Cancer cell line	Male
CVCL_XP32	HAP1 GPD2 (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00006163	PHASE4	COMPLETED	Computer-assisted Diabetes Self-management Interventions
NCT00036504	PHASE4	COMPLETED	Efficacy and Safety of Twice-Daily Insulin Lispro Low Mixture Compared to a Once-Daily Long Acting Insulin Comparator in Patients Who Have Been Using One or More Oral Antihyperglycemic Agents Without Insulin
NCT00044460	PHASE4	COMPLETED	Efficacy and Safety In Poorly Controlled Type 2 Diabetics
NCT00095446	PHASE4	COMPLETED	NovoLog Observation Trial in Subjects With Type 1 and Type 2 Diabetes
NCT00101751	PHASE4	COMPLETED	INITIATE Plus (INITiation of Insulin to Reach A1c TargEt) Study
NCT00110370	PHASE4	COMPLETED	Comparing Pre-Mixed Insulin With Insulin Glargine Combined With Rapid-Acting Insulin in Patients With Type 2 Diabetes
NCT00110448	PHASE4	COMPLETED	Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) Trial
NCT00118950	PHASE4	COMPLETED	Effect of Metformin Versus Repaglinide Treatment in Non-Obese Type 2 Diabetic Patients Uncontrolled by Diet
NCT00118963	PHASE4	COMPLETED	Effect of Repaglinide Versus Metformin Treatment in Non-Obese Patients With Type-2-Diabetes
NCT00121966	PHASE4	COMPLETED	South Danish Diabetes Study: Evaluation of the Antidiabetic Treatment of Type 2 Diabetes Mellitus
NCT00123604	PHASE4	COMPLETED	Vascular Effects of Carvedilol Versus Metoprolol in Hypertensive Patients With Type 2 Diabetes
NCT00123643	PHASE4	COMPLETED	Vascular Effects of Rosiglitazone Versus Glyburide in Type 2 Diabetic Patients
NCT00124397	PHASE4	COMPLETED	Atorvastatin and Endothelial Function in Type 2 Diabetes Mellitus (ATTEND-Study)
NCT00129233	PHASE4	COMPLETED	Comparison of Valsartan With Amlodipine in Hypertensive Patients With Glucose Intolerance
NCT00133718	PHASE4	COMPLETED	A 2 Year Trial of Patients With Type 2 Diabetes Focusing on Cardiovascular Diagnostics and Metabolic Control
NCT00135070	PHASE4	TERMINATED	Hospital In-Patient Insulin Study
NCT00141232	PHASE4	COMPLETED	Evaluating Atorvastatin With Omega-3 Fatty Acids in Cardiovascular Risk Reduction in Patients With Type 2 Diabetes
NCT00144144	PHASE4	UNKNOWN	A Study on Ca Blocker Versus AII Antagonists in Hypertension With Type 2 Diabetes
NCT00149331	PHASE4	COMPLETED	The Effects of Two Education Strategies About Insulin on Patient Preferences and Perceptions About Insulin Therapy
NCT00162357	PHASE4	COMPLETED	Post-PCI:Cardiac Imaging in Patients With Diabetes to Detect Coronary Artery Blockages Previously Opened by Angioplasty
NCT00174681	PHASE4	COMPLETED	Tulip Study: Testing the Usefulness of Lantus When Initiated Prematurely In Patients With Type 2 Diabetes
NCT00174824	PHASE4	COMPLETED	Comparison of Insulin Glargine and NPH Human Insulin in Progression of Diabetic Retinopathy in Type 2 Diabetic Patients
NCT00177398	PHASE4	COMPLETED	Effect of Glargine Insulin on Glucose Control in Hospitalized Patients Who Receive Tube Feedings
NCT00179400	PHASE4	COMPLETED	The Role of Acute Combined PPAR Alpha and Gamma Stimulation on Insulin Action in Humans
NCT00184561	PHASE4	COMPLETED	Effectiveness and Safety of Biphasic Insulin Aspart 70/30 in Subjects With Type 2 Diabetes
NCT00184626	PHASE4	COMPLETED	Comparison of Insulin Glargine Versus Biphasic Insulin Aspart 30/70 or Biphasic Insulin Aspart 30/70 in Combination With Metformin in Subjects With Type 2 Diabetes.
NCT00191178	PHASE4	COMPLETED	Effects of Insulin in Perceived Mood Symptoms in Patients With Type 2 Diabetes
NCT00191282	PHASE4	COMPLETED	Hyperglycemia and Cardiovascular Outcomes With Type 2 Diabetes
NCT00191464	PHASE4	COMPLETED	Long-Term Effects of Insulin Plus Metformin Regimens on the Overall and Postprandial Glycemic Control of Patients With Type 2 Diabetes
NCT00192803	PHASE4	UNKNOWN	Non-Insulin Dependent Diabetes Mellitus (NIDDM) and Angiotensin Converting Enzyme 2 (ACE2): Diabetic Patients Treated With Antihypertensive Drugs
NCT00202033	PHASE4	COMPLETED	Impact of Self-Monitoring Blood Glucose Frequency on Glycemic Control in Patients With Type 2 Diabetes
NCT00205660	PHASE4	COMPLETED	Changes in Adiposity, Metabolic Measures From Atypicals to Aripiprazole
NCT00212290	PHASE4	COMPLETED	Insulin Resistance and Central Nervous System (CNS) Function in Type 2 Diabetes
NCT00212303	PHASE4	COMPLETED	Exercise Training in Type 2 Diabetes and Hypertension
NCT00225342	PHASE4	WITHDRAWN	Study Protocol for Rosiglitazone Versus Gliclazide in Diabetics With Angina
NCT00238472	PHASE4	COMPLETED	A Pilot Study to Evaluate the Effects of Nateglinide vs. Glibenclamide on Renal Hemodynamics and Albumin Excretion
NCT00239538	PHASE4	COMPLETED	SMOOTH - Blood Pressure Control in Diabetic/Obese Patients
NCT00240253	PHASE4	COMPLETED	A Study Evaluating the Efficacy and Safety of Adding Symlin® to Lantus® (Insulin Glargine) in Subjects With Type 2 Diabetes
NCT00240422	PHASE4	COMPLETED	Trial to Compare the Effects of Either Telmisartan (40-80 mg PO Once Daily) or Ramipril (5-10 mg PO Once Daily) on Renal Endothelial Dysfunction in Hypertensive Patients With Type 2 Diabetes
NCT00241085	PHASE4	COMPLETED	Effect of Valsartan on Proteinuria in Patients With Hypertension and Diabetes Mellitus