GAPDHS

Summary

GAPDHS (glyceraldehyde-3-phosphate dehydrogenase, spermatogenic, HGNC:24864) is a protein-coding gene on chromosome 19q13.12, encoding Glyceraldehyde-3-phosphate dehydrogenase, testis-specific (O14556). Catalyzes the conversion of D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate in glycolysis and the reverse reaction in gluconeogenesis.

This gene encodes a protein belonging to the glyceraldehyde-3-phosphate dehydrogenase family of enzymes that play an important role in carbohydrate metabolism. Like its somatic cell counterpart, this sperm-specific enzyme functions in a nicotinamide adenine dinucleotide-dependent manner to remove hydrogen and add phosphate to glyceraldehyde 3-phosphate to form 1,3-diphosphoglycerate. During spermiogenesis, this enzyme may play an important role in regulating the switch between different energy-producing pathways, and it is required for sperm motility and male fertility.

Source: NCBI Gene 26330 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 88 total
• MANE Select transcript: NM_014364

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24864
Approved symbol	GAPDHS
Name	glyceraldehyde-3-phosphate dehydrogenase, spermatogenic
Location	19q13.12
Locus type	gene with protein product
Status	Approved
Aliases	GAPDH-2, GAPD2
Ensembl gene	ENSG00000105679
Ensembl biotype	protein_coding
OMIM	609169
Entrez	26330

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 nonsense_mediated_decay

ENST00000222286, ENST00000585510, ENST00000586334

RefSeq mRNA: 1 — MANE Select: NM_014364 NM_014364

CCDS: CCDS12465

Canonical transcript exons

ENST00000222286 — 11 exons

Exon	Start	End
ENSE00000700072	35544909	35545006
ENSE00000700073	35543665	35543827
ENSE00000700074	35543340	35543491
ENSE00000700093	35536813	35536990
ENSE00000862793	35533456	35533594
ENSE00001284302	35545098	35545319
ENSE00003515974	35538577	35538683
ENSE00003535670	35542319	35542409
ENSE00003600107	35542490	35542608
ENSE00003673914	35538307	35538403
ENSE00003787369	35542945	35543026

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.45.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.7447 / max 762.3336, expressed in 20 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175341	0.2431	4
175340	0.2336	5
175338	0.1135	3
175339	0.0735	3
175344	0.0458	14
208784	0.0152	3
175343	0.0100	6
175342	0.0081	5
208785	0.0018	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	98.45	gold quality
right testis	UBERON:0004534	98.24	gold quality
testis	UBERON:0000473	95.45	gold quality
adult organism	UBERON:0007023	93.01	gold quality
sperm	CL:0000019	88.89	gold quality
male germ cell	CL:0000015	88.23	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.55	gold quality
skin of leg	UBERON:0001511	62.22	gold quality
skin of abdomen	UBERON:0001416	61.67	gold quality
zone of skin	UBERON:0000014	59.39	gold quality
pancreatic ductal cell	CL:0002079	59.35	silver quality
upper leg skin	UBERON:0004262	57.31	silver quality
endometrium epithelium	UBERON:0004811	56.39	gold quality
tibialis anterior	UBERON:0001385	55.62	silver quality
quadriceps femoris	UBERON:0001377	53.23	gold quality
vastus lateralis	UBERON:0001379	52.16	gold quality
Brodmann (1909) area 10	UBERON:0013541	51.75	gold quality
granulocyte	CL:0000094	51.27	silver quality
deltoid	UBERON:0001476	51.13	gold quality
epithelial cell of pancreas	CL:0000083	51.08	gold quality
thymus	UBERON:0002370	50.81	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
cortical plate	UBERON:0005343	50.02	gold quality
metanephric glomerulus	UBERON:0004736	49.61	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
cerebellar vermis	UBERON:0004720	49.25	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	32.98
E-GEOD-135922	yes	20.09
E-ANND-3	no	1.18

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

5 targeting GAPDHS, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-711	96.60	65.75	528

Literature-anchored findings (GeneRIF, showing 16)

• GAPD2 enzymatic activity is present in human sperm. GAPD2 is tightly bound to sperm and most enzymatic activity is not released by permeabilization with CHAPS detergent. GAPD2 is restricted in location to the principal piece of the sperm flagellum. (PMID:10714828)
• We have concluded that a simple nuclear localization of GAPDH does not induce apoptosis, and that MPP+-induced apoptosis is not caused by nuclear translocation of GAPDH. (PMID:16324157)
• Characterization of the rat GAPDHS and comparison to the human and mouse enzymes. (PMID:16700075)
• Comparative study of the amino acid sequences of mammalian GAPDs revealed conservative cysteine residues (C21, C94, and C150) that are specific for the sperm isoenzyme and absent in the somatic isoenzyme. (PMID:18298375)
• Human his-GAPDHS expressed in baculovirus-infected insect cells is homotetrameric. (PMID:20828617)
• Data suggest that high stability of the sperm-specific GAPDS is of importance for the efficiency of fertilization. (PMID:20833277)
• Structure and kinetic characterization of human sperm-specific glyceraldehyde-3-phosphate dehydrogenase, GAPDS. (PMID:21269272)
• The chaperonin TRiC was shown to assist an ATP-dependent refolding of recombinant forms of GAPDS. (PMID:21995946)
• the expression of GAPDS in melanoma cells may facilitate glycolysis and prevent the induction of apoptosis. (PMID:23026046)
• GAPDS protein was expressed in both Sertoli cells and elongated sperms. The expression of GAPDS gradually increased with age in the epididymis. (PMID:23306140)
• Data indicate that the positive expression of studied genes fertilization rate for GAPDHS positive subset was 66%, ACR - 71%, SPATA22 - 68%, MND1 - 70%, pregnancy rates were 8%, 6%, 18% and 36% respectively. (PMID:23675907)
• Structural basis for the NAD binding cooperativity and catalytic characteristics of sperm-specific glyceraldehyde-3-phosphate dehydrogenase (PMID:25936797)
• This result implies that GAPDHS participates in specific signal-transduction pathways. (PMID:26660717)
• It is assumed that the deficiency in GAPDS observed in most dysplasia of the fibrous sheath sperm samples is ascribable to a disorder in the regulation of GAPDS expression caused by the mutation in the intron region of GAPDS gene. (PMID:27135296)
• GAPDS overexpression antagonize high glucose-induced apoptosis by controlling reactive oxygen species accumulation in TM3 cells. (PMID:29626473)
• A Short Isoform of Spermatogenic Enzyme GAPDHS Functions as a Metabolic Switch and Limits Metastasis in Melanoma. (PMID:35149585)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gapdhs	ENSDARG00000039914
mus_musculus	Gapdhs	ENSMUSG00000061099
rattus_norvegicus	Gapdhs	ENSRNOG00000021009

Paralogs (1): GAPDH (ENSG00000111640)

Protein

Protein identifiers

Glyceraldehyde-3-phosphate dehydrogenase, testis-specific — O14556 (reviewed: O14556)

Alternative names: Spermatogenic cell-specific glyceraldehyde 3-phosphate dehydrogenase 2, Spermatogenic glyceraldehyde-3-phosphate dehydrogenase

All UniProt accessions (4): O14556, A0A0K0K1K1, K7EMB2, K7EP73

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the conversion of D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate in glycolysis and the reverse reaction in gluconeogenesis. May play an important role in regulating the switch between different pathways for energy production during spermiogenesis and in the spermatozoon. Required for sperm motility and male fertility.

Subunit / interactions. Homotetramer. Interacts with ARRB2; the interaction is detected in the nucleus upon OR1D2 stimulation.

Subcellular location. Cytoplasm.

Tissue specificity. Testis specific.

Domain organisation. The testis-specific N-terminal extension mediates tight association with the cytoskeletal fibrous sheath of the spermatozoa flagellum, possibly via interchain disulfide-bonding of Cys-21 with sheath components.

Pathway. Carbohydrate degradation; glycolysis; pyruvate from D-glyceraldehyde 3-phosphate: step 1/5.

Similarity. Belongs to the glyceraldehyde-3-phosphate dehydrogenase family.

RefSeq proteins (1): NP_055179* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006424	Glyceraldehyde-3-P_DH_1	Family
IPR020828	GlycerAld_3-P_DH_NAD(P)-bd	Domain
IPR020829	GlycerAld_3-P_DH_cat	Domain
IPR020830	GlycerAld_3-P_DH_AS	Active_site
IPR020831	GlycerAld/Erythrose_P_DH	Family
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily

Pfam: PF00044, PF02800

Enzyme classification (BRENDA):

• EC 1.2.1.12 — glyceraldehyde-3-phosphate dehydrogenase (phosphorylating) (BRENDA: 126 organisms, 100 substrates, 290 inhibitors, 310 Km, 60 kcat entries)

Substrate kinetics (BRENDA)

19 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
NAD+	—	114
D-GLYCERALDEHYDE 3-PHOSPHATE	0.0003–15	94
3-PHOSPHO-D-GLYCEROYL PHOSPHATE	0.002–1.78	24
PHOSPHATE	0.2–37	23
NADH	0.0033–0.537	15
ARSENATE	1–8.3	4
1,3-DIPHOSPHOGLYCERIC ACID	0.01–0.018	3
D-GLYCERALDEHYDE-3-PHOSPHATE	0.0734–0.5	3
N6-(2-CARBOXYETHYL)-NAD+	0.0102–0.145	3
3-ACETYL-NAD+	0.158–0.62	2
3-ACETYLPYRIDINE HYPOXANTHINE NUCLEOTIDE	1.43–8.15	2
ERYTHROSE 4-PHOSPHATE	0.119–0.127	2
NADP+	1.7–7.1	2
THIO-NAD+	0.0435–0.235	2
ACETALDEHYDE	0.31	1

Catalyzed reactions (Rhea), 1 shown:

• D-glyceraldehyde 3-phosphate + phosphate + NAD(+) = (2R)-3-phospho-glyceroyl phosphate + NADH + H(+) (RHEA:10300)

UniProt features (59 total): strand 19, helix 13, binding site 10, turn 7, sequence conflict 3, region of interest 2, chain 1, site 1, sequence variant 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
3H9E	X-RAY DIFFRACTION	1.72
5C7O	X-RAY DIFFRACTION	1.73
5C7L	X-RAY DIFFRACTION	1.86
3PFW	X-RAY DIFFRACTION	2.15

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14556-F1	89.18	0.80

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 (2): 251 (activates thiol group during catalysis); 224 (nucleophile)

Ligand- & substrate-binding residues (10): 223–225; 254; 283–284; 306; 388; 85–86; 106; 151; 173; 193

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-390471	Association of TriC/CCT with target proteins during biosynthesis
R-HSA-70171	Glycolysis
R-HSA-70263	Gluconeogenesis

MSigDB gene sets: 131 (showing top): GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_REGULATION_OF_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_PHOSPHORUS_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_TRIPHOSPHATE_METABOLIC_PROCESS, GOBP_CILIUM_MOVEMENT, MOOTHA_GLUCONEOGENESIS

GO Biological Process (4): glucose metabolic process (GO:0006006), glycolytic process (GO:0006096), flagellated sperm motility (GO:0030317), positive regulation of glycolytic process (GO:0045821)

GO Molecular Function (6): glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity (GO:0004365), NADP binding (GO:0050661), NAD binding (GO:0051287), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor (GO:0016620)

GO Cellular Component (3): nucleus (GO:0005634), cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Glucose metabolism	2
Chaperonin-mediated protein folding	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
glyceraldehyde-3-phosphate dehydrogenase [NAD(P)+] (phosphorylating) activity	2
adenyl nucleotide binding	2
cellular anatomical structure	2
hexose metabolic process	1
phosphoglycerate kinase activity	1
phosphoglycerate mutase activity	1
phosphopyruvate hydratase activity	1
pyruvate kinase activity	1
pyruvate metabolic process	1
generation of precursor metabolites and energy	1
aerobic respiration	1
carbohydrate catabolic process	1
pyridine nucleotide catabolic process	1
ADP catabolic process	1
ATP metabolic process	1
nicotinamide nucleotide metabolic process	1
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
glycolytic process	1
regulation of glycolytic process	1
positive regulation of purine nucleotide catabolic process	1
positive regulation of carbohydrate metabolic process	1
positive regulation of ATP metabolic process	1
binding	1
catalytic activity	1
oxidoreductase activity, acting on the aldehyde or oxo group of donors	1
intracellular membrane-bounded organelle	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

5718 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GAPDHS	PGK2	P07205	700
GAPDHS	SHMT2	P34897	648
GAPDHS	LDHC	P07864	636
GAPDHS	GLUD2	P49448	624
GAPDHS	TPI1	P00938	604
GAPDHS	SHMT1	P34896	604
GAPDHS	HSPE1	P61604	579
GAPDHS	AKAP4	Q5JQC9	571
GAPDHS	PGK1	P00558	546
GAPDHS	TSSK4	Q6SA08	528
GAPDHS	FSCB	Q5H9T9	527
GAPDHS	AKAP3	O75969	526
GAPDHS	HK1	P19367	522
GAPDHS	SIAH1	Q8IUQ4	517
GAPDHS	GPI	P06744	506

IntAct

200 interactions, top by confidence:

A	B	Type	Score
GAPDH	GAPDHS	psi-mi:“MI:0914”(association)	0.620
GAPDH	GAPDHS	psi-mi:“MI:0915”(physical association)	0.620
MFSD5	GAPDHS	psi-mi:“MI:0915”(physical association)	0.590
C12orf50	GAPDHS	psi-mi:“MI:0915”(physical association)	0.590
GPX8	GAPDHS	psi-mi:“MI:0915”(physical association)	0.590
MEIOB	GAPDHS	psi-mi:“MI:0915”(physical association)	0.590
SLC5A2	GAPDHS	psi-mi:“MI:0915”(physical association)	0.560
HYAL4	GAPDHS	psi-mi:“MI:0915”(physical association)	0.560
DARS2	GAPDHS	psi-mi:“MI:0915”(physical association)	0.560
THAP1	GAPDHS	psi-mi:“MI:0914”(association)	0.560
ZMYND19	GAPDHS	psi-mi:“MI:0915”(physical association)	0.560
GAPDHS	ZMYND19	psi-mi:“MI:0915”(physical association)	0.560
THAP1	GAPDHS	psi-mi:“MI:0915”(physical association)	0.560
SLC5A2	GAPDHS	psi-mi:“MI:0914”(association)	0.560
DARS2	GAPDHS	psi-mi:“MI:0914”(association)	0.560
HYAL4	GAPDHS	psi-mi:“MI:0914”(association)	0.560
TRIP6	WTIP	psi-mi:“MI:0914”(association)	0.530
GDE1	GAPDHS	psi-mi:“MI:0914”(association)	0.530
MGST3	GAPDHS	psi-mi:“MI:0914”(association)	0.530
INSL3	GAPDHS	psi-mi:“MI:0914”(association)	0.530
ITK	GAPDHS	psi-mi:“MI:0914”(association)	0.530
KCNA10	GAPDHS	psi-mi:“MI:0914”(association)	0.530
CFAP46	GAPDHS	psi-mi:“MI:0914”(association)	0.530
SWSAP1	GAPDHS	psi-mi:“MI:0914”(association)	0.530

BioGRID (231): GAPDHS (Affinity Capture-MS), GAPDHS (Affinity Capture-MS), GAPDHS (Affinity Capture-MS), GAPDHS (Affinity Capture-MS), GAPDHS (Affinity Capture-MS), GAPDHS (Affinity Capture-MS), GAPDHS (Affinity Capture-MS), GAPDHS (Affinity Capture-MS), GAPDHS (Affinity Capture-MS), GAPDHS (Affinity Capture-MS), GAPDHS (Affinity Capture-MS), GAPDHS (Affinity Capture-MS), GAPDHS (Affinity Capture-MS), GAPDHS (Affinity Capture-MS), GAPDHS (Affinity Capture-MS)

ESM2 similar proteins: B0B815, B2S264, B5DFN2, B8I0F9, C4PRC1, F0T377, O14556, O17607, O50258, O83154, P07756, P0CC04, P0CZ18, P0DJI2, P20054, P23603, P23700, P26758, P29577, P29578, P29722, P31327, P46058, P50245, P52183, P76002, P77966, P94664, Q18990, Q1Q0T4, Q253E5, Q27772, Q3KLQ7, Q548P6, Q57806, Q64467, Q6D421, Q6KCA4, Q7S8A6, Q822J8

Diamond homologs: A2YQT7, A3FKF7, O01360, O13507, O14556, O16027, O42259, O43026, O44104, O44105, O57479, P00355, P00356, P00357, P04406, P04796, P04797, P04970, P07486, P07487, P08735, P09317, P0A1P1, P0CN74, P0CN75, P10096, P16858, P17244, P17329, P17330, P17331, P17729, P19089, P20287, P25858, P25861, P26517, P26518, P26520, P26521

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
GAPDHS	“up-regulates quantity”	“3-phosphonato-D-glyceroyl phosphate(4-)”	“chemical modification”
GAPDHS	“down-regulates quantity”	“D-glyceraldehyde 3-phosphate(2-)”	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	75
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1075 predictions. Top by Δscore:

Variant	Effect	Δscore
19:35538681:GTG:G	donor_gain	1.0000
19:35538690:A:T	donor_gain	1.0000
19:35542317:A:AG	acceptor_gain	1.0000
19:35542318:G:GA	acceptor_gain	1.0000
19:35542318:GC:G	acceptor_gain	1.0000
19:35542318:GCAAA:G	acceptor_gain	1.0000
19:35542406:TTCGG:T	donor_loss	1.0000
19:35542407:TCGGT:T	donor_loss	1.0000
19:35542408:CGG:C	donor_loss	1.0000
19:35542409:GGTA:G	donor_loss	1.0000
19:35542410:G:C	donor_loss	1.0000
19:35542410:G:GG	donor_gain	1.0000
19:35542411:T:A	donor_loss	1.0000
19:35542488:A:AG	acceptor_gain	1.0000
19:35542488:AG:A	acceptor_gain	1.0000
19:35542489:G:GT	acceptor_gain	1.0000
19:35542489:GG:G	acceptor_gain	1.0000
19:35542489:GGA:G	acceptor_gain	1.0000
19:35542489:GGAC:G	acceptor_gain	1.0000
19:35542489:GGACC:G	acceptor_gain	1.0000
19:35542606:GAG:G	donor_gain	1.0000
19:35542606:GAGG:G	donor_loss	1.0000
19:35542607:AGG:A	donor_loss	1.0000
19:35542608:GG:G	donor_loss	1.0000
19:35542609:GTA:G	donor_loss	1.0000
19:35542933:T:A	acceptor_gain	1.0000
19:35542937:T:A	acceptor_gain	1.0000
19:35542943:A:AG	acceptor_gain	1.0000
19:35542944:G:GA	acceptor_gain	1.0000
19:35542944:GC:G	acceptor_gain	1.0000

AlphaMissense

2648 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:35542607:A:C	S220R	0.998
19:35542945:C:A	S220R	0.998
19:35542945:C:G	S220R	0.998
19:35542969:T:G	C228W	0.998
19:35543369:G:C	Q257H	0.998
19:35543369:G:T	Q257H	0.998
19:35543379:G:C	D261H	0.998
19:35543429:C:A	N277K	0.998
19:35543429:C:G	N277K	0.998
19:35538376:T:A	N105K	0.997
19:35538376:T:G	N105K	0.997
19:35543380:A:T	D261V	0.997
19:35543410:G:A	G271E	0.997
19:35543721:T:C	L317P	0.997
19:35545005:T:A	W385R	0.997
19:35545005:T:C	W385R	0.997
19:35536990:G:A	G82E	0.996
19:35538312:G:A	G84E	0.996
19:35538321:G:A	G87D	0.996
19:35538324:G:C	R88P	0.996
19:35542341:T:A	W158R	0.996
19:35542341:T:C	W158R	0.996
19:35543349:C:G	H251D	0.996
19:35538315:G:C	R85P	0.995
19:35538595:G:C	D121H	0.995
19:35543379:G:T	D261Y	0.995
19:35543409:G:T	G271W	0.995
19:35543419:C:A	A274D	0.995
19:35543709:C:T	S313F	0.995
19:35545127:G:C	R395P	0.995

dbSNP variants (sampled 300 via entrez): RS1000431149 (19:35534403 C>T), RS1000916625 (19:35538975 G>A), RS1001017735 (19:35538744 G>T), RS1001088815 (19:35544644 C>T), RS1001192119 (19:35541806 A>G), RS1001365785 (19:35536024 G>A), RS1001459124 (19:35535809 G>A), RS1001864199 (19:35531479 G>A), RS1001893994 (19:35531686 C>T), RS1002041920 (19:35543342 C>T), RS1002428514 (19:35537530 T>A), RS1002504966 (19:35541916 G>A,C), RS1003022681 (19:35536176 T>C), RS1003039770 (19:35542158 G>A), RS1003339223 (19:35536433 A>C,G)

Disease associations

OMIM: gene MIM:609169 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): prostate cancer (MONDO:0008315)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST007828_1	Diastolic blood pressure	1.000000e-08
GCST007829_7	Systolic blood pressure	5.000000e-07
GCST90002400_282	Plateletcrit	4.000000e-20
GCST90002402_560	Platelet count	5.000000e-20

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0006945	diastolic blood pressure change measurement
EFO:0006944	systolic blood pressure change measurement
EFO:0007985	platelet crit
EFO:0004309	platelet count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, increases expression	2
aristolochic acid I	increases expression	1
aminomethylphosphonic acid (AMPA)	decreases expression	1
lariciresinol	increases expression	1
jinfukang	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Benzo(a)pyrene	increases methylation	1
Urethane	decreases expression	1
Valproic Acid	increases methylation	1
2,4-Dichlorophenoxyacetic Acid	decreases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer