PDHA2

Summary

PDHA2 (pyruvate dehydrogenase E1 subunit alpha 2, HGNC:8807) is a protein-coding gene on chromosome 4q22.3, encoding Pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial (P29803). Together with PDHB forms the heterotetrameric E1 subunit of the pyruvate dehydrogenase (PDH) complex in testis.

Enables pyruvate dehydrogenase (NAD+) activity and pyruvate dehydrogenase (acetyl-transferring) activity. Predicted to be involved in pyruvate decarboxylation to acetyl-CoA. Located in mitochondrion and nucleolus. Implicated in spermatogenic failure 70.

Source: NCBI Gene 5161 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spermatogenic failure 70 (Limited, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 64 total — 1 likely-pathogenic
• Phenotypes (HPO): 12
• Druggable target: yes
• MANE Select transcript: NM_005390

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8807
Approved symbol	PDHA2
Name	pyruvate dehydrogenase E1 subunit alpha 2
Location	4q22.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000163114
Ensembl biotype	protein_coding
OMIM	179061
Entrez	5161

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000295266

RefSeq mRNA: 1 — MANE Select: NM_005390 NM_005390

CCDS: CCDS3644

Canonical transcript exons

ENST00000295266 — 1 exons

Exon	Start	End
ENSE00001071770	95840093	95841464

Expression profiles

Bgee: expression breadth broad, 23 present calls, max score 97.56.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1613 / max 152.0156, expressed in 4 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
48970	0.1613	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	97.56	gold quality
male germ cell	CL:0000015	96.68	gold quality
left testis	UBERON:0004533	93.13	gold quality
right testis	UBERON:0004534	92.86	gold quality
adult organism	UBERON:0007023	91.22	gold quality
testis	UBERON:0000473	90.78	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.74	gold quality
tendon of biceps brachii	UBERON:0008188	76.57	silver quality
buccal mucosa cell	CL:0002336	59.37	gold quality
tibialis anterior	UBERON:0001385	57.62	silver quality
pancreatic ductal cell	CL:0002079	56.90	silver quality
decidua	UBERON:0002450	56.55	gold quality
myocardium	UBERON:0002349	55.16	gold quality
ileal mucosa	UBERON:0000331	54.49	silver quality
quadriceps femoris	UBERON:0001377	53.50	gold quality
hair follicle	UBERON:0002073	52.86	gold quality
vastus lateralis	UBERON:0001379	52.71	gold quality
deltoid	UBERON:0001476	52.08	gold quality
upper leg skin	UBERON:0004262	51.41	silver quality
left ventricle myocardium	UBERON:0006566	51.13	gold quality
medial globus pallidus	UBERON:0002477	51.11	gold quality
epithelial cell of pancreas	CL:0000083	50.66	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
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
thymus	UBERON:0002370	49.92	gold quality
metanephric glomerulus	UBERON:0004736	49.61	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
cardiac muscle of right atrium	UBERON:0003379	49.29	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.65

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

10 targeting PDHA2, 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-4753-3P	99.90	71.03	3786
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-4502	99.65	66.99	1021
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-3682-3P	99.58	67.63	865
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-216B-5P	97.16	66.76	1126
HSA-MIR-873-3P	96.84	66.09	786
HSA-MIR-591	96.29	68.16	611

Literature-anchored findings (GeneRIF, showing 5)

• it is the full demethylation of the CpG island located in the coding region that seems to play a crucial role upon PDHA2 gene transcription in testis. (PMID:20005141)
• Methylation of the PDHA2 coding region can inhibit gene transcription. (PMID:22675509)
• Expression of the PDHA1 gene was found in all somatic cells, whereas expression of PDHA2 gene was restricted to germ cells. The switch from X-linked to autosomic gene expression occurred in spermatocytes. (PMID:22750801)
• Our findings show that also recessive complex digit malformation can be caused by BMPR1B variant and not all biallelic BMPR1B variants cause acromesomelic dysplasia. PDHA2 is a novel candidate gene for male infertility; the protein product is a mitochondrial enzyme with highest expression in ejaculated sperm. (PMID:29581481)
• Our results indicated that miR215p targeted PDHA1 to regulate a metabolic switch and cancer progression in gastric cancer, and reveal the potential role of the miR215p/PDHA1 axis in gastric cancer treatment (PMID:30226598)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	pdha1b	ENSDARG00000010555
danio_rerio	pdha1a	ENSDARG00000012387
mus_musculus	Pdha2	ENSMUSG00000047674
rattus_norvegicus	Pdha2	ENSRNOG00000077743
drosophila_melanogaster	Pdha	FBGN0028325
drosophila_melanogaster	CG7024	FBGN0029722
caenorhabditis_elegans		WBGENE00011510

Paralogs (2): PDHA1 (ENSG00000131828), BCKDHA (ENSG00000248098)

Protein

Protein identifiers

Pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial — P29803 (reviewed: P29803)

Alternative names: PDHE1-A type II

All UniProt accessions (1): P29803

UniProt curated annotations — full annotation on UniProt →

Function. Together with PDHB forms the heterotetrameric E1 subunit of the pyruvate dehydrogenase (PDH) complex in testis. The PDH complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links cytoplasmic glycolysis and the mitochondrial tricarboxylic acid (TCA) cycle. It contains multiple copies of three enzymatic components: pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2) and dihydrolipoamide dehydrogenase (E3). The E1 subunit catalyzes both the thiamine pyrophosphate (TPP)-dependent decarboxylation of pyruvate and the reductive acetylation of a lipoyl group covalently linked to the lipoyl-bearing domains of E2.

Subunit / interactions. Heterotetramer of two PDHA2 and two PDHB subunits. The heterotetramer interacts with DLAT, and is part of the multimeric pyruvate dehydrogenase (PDH) complex that contains multiple copies of pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide dehydrogenase (DLD, E3). These subunits are bound to an inner core composed of about 48 DLAT and 12 PDHX molecules.

Subcellular location. Mitochondrion matrix.

Tissue specificity. Testis. Expressed in postmeiotic spermatogenic cells.

Post-translational modifications. Phosphorylation at Ser-291, Ser-293 and Ser-298 by PDK family kinases inactivates the enzyme; for this phosphorylation at a single site is sufficient. Phosphorylation at Ser-293 interferes with access to active site, and thereby inactivates the enzyme. Dephosphorylation at all three sites, i.e. at Ser-291, Ser-293 and Ser-298, is required for reactivation.

Disease relevance. Spermatogenic failure 70 (SPGF70) [MIM:619828] An autosomal recessive male infertility disorder characterized by azoospermia, sperm immotility or necrozoospermia. Hypospermatogenesis and meiotic arrest have also been observed. The disease may be caused by variants affecting the gene represented in this entry.

Activity regulation. Pyruvate dehydrogenase activity is inhibited by phosphorylation of PDHA2; it is reactivated by dephosphorylation.

RefSeq proteins (1): NP_005381* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001017	DH_E1	Domain
IPR017597	Pyrv_DH_E1_asu_subgrp-y	Family
IPR029061	THDP-binding	Homologous_superfamily
IPR050642	PDH_E1_Alpha_Subunit	Family

Pfam: PF00676

Catalyzed reactions (Rhea), 1 shown:

• N(6)-[(R)-lipoyl]-L-lysyl-[protein] + pyruvate + H(+) = N(6)-[(R)-S(8)-acetyldihydrolipoyl]-L-lysyl-[protein] + CO2 (RHEA:19189)

UniProt features (36 total): binding site 22, mutagenesis site 6, modified residue 3, sequence variant 2, transit peptide 1, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P29803-F1	94.08	0.92

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 (22): 165; 194; 194; 194; 195; 195; 196; 196; 223; 223; 90; 223 …

Post-translational modifications (3): 291, 293, 298

Mutagenesis-validated functional residues (6):

Position	Phenotype
230	slightly reduces enzyme activity.
291	strongly reduces enzyme activity. increases enzyme activity in stem cells.
291	abolishes enzyme activity. increases neuronal cell death in response to glutamate excitotoxicity.
293	increases enzyme activity in stem cells.
293	abolishes enzyme activity. increases neuronal cell death in response to glutamate excitotoxicity.
298	slightly reduces enzyme activity.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-204174	Regulation of pyruvate dehydrogenase (PDH) complex
R-HSA-5362517	Signaling by Retinoic Acid
R-HSA-9861559	PDH complex synthesizes acetyl-CoA from PYR

MSigDB gene sets: 152 (showing top): YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, KEGG_GLYCOLYSIS_GLUCONEOGENESIS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ACETYL_COA_METABOLIC_PROCESS, CAGCTG_AP4_Q5, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GATA3_01, GOBP_SULFUR_COMPOUND_BIOSYNTHETIC_PROCESS, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_AMIDE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_METABOLIC_PROCESS

GO Biological Process (3): glucose metabolic process (GO:0006006), pyruvate decarboxylation to acetyl-CoA (GO:0006086), tricarboxylic acid cycle (GO:0006099)

GO Molecular Function (5): pyruvate dehydrogenase (acetyl-transferring) activity (GO:0004739), metal ion binding (GO:0046872), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor (GO:0016624)

GO Cellular Component (6): nucleus (GO:0005634), nucleolus (GO:0005730), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), pyruvate dehydrogenase complex (GO:0045254), intracellular membrane-bounded organelle (GO:0043231)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Regulation of pyruvate metabolism	1
Signaling by Nuclear Receptors	1
Pyruvate metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
aerobic respiration	2
intracellular membrane-bounded organelle	2
hexose metabolic process	1
dihydrolipoyl dehydrogenase (NADH) activity	1
pyruvate dehydrogenase (acetyl-transferring) activity	1
dihydrolipoyllysine-residue acetyltransferase activity	1
acetyl-CoA biosynthetic process	1
pyruvate metabolic process	1
primary metabolic process	1
oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor	1
cation binding	1
binding	1
catalytic activity	1
oxidoreductase activity, acting on the aldehyde or oxo group of donors	1
nuclear lumen	1
intracellular membraneless organelle	1
cytoplasm	1
mitochondrion	1
intracellular organelle lumen	1
alpha-ketoacid dehydrogenase complex	1
acetyltransferase complex	1
intracellular anatomical structure	1
membrane-bounded organelle	1
intracellular organelle	1

Protein interactions and networks

STRING

2407 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PDHA2	PDHB	P11177	913
PDHA2	DLAT	P10515	861
PDHA2	PGK2	P07205	820
PDHA2	DLD	P09622	798
PDHA2	GLUD1	P00367	769
PDHA2	ASPM	Q8IZT6	761
PDHA2	GLUD2	P49448	739
PDHA2	PDHX	O00330	738
PDHA2	MCPH1	Q8NEM0	684
PDHA2	PGK1	P00558	618
PDHA2	APRT	P07741	572
PDHA2	GARIN5A	Q6IPT2	542
PDHA2	WDR25	Q64LD2	499
PDHA2	LDHC	P07864	490
PDHA2	OGDH	Q02218	480

IntAct

19 interactions, top by confidence:

A	B	Type	Score
PDHA2	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
PDHA2		psi-mi:“MI:0915”(physical association)	0.560
APBA3	DUSP11	psi-mi:“MI:0914”(association)	0.530
PDK3	PDHX	psi-mi:“MI:0914”(association)	0.530
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
CAND1	GTPBP10	psi-mi:“MI:0914”(association)	0.350
COPS5	FBLL1	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
PDK3		psi-mi:“MI:0914”(association)	0.350
MYC		psi-mi:“MI:0914”(association)	0.350
PATE1	MANBA	psi-mi:“MI:0914”(association)	0.350
C1orf54	AGRN	psi-mi:“MI:0914”(association)	0.350
PDHA2	MEOX2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (25): PDHA2 (Co-fractionation), PDHA2 (Co-fractionation), PDHA2 (Affinity Capture-MS), PDHA2 (Affinity Capture-MS), PDHA2 (Affinity Capture-MS), PDHA2 (Affinity Capture-MS), PDHA2 (Affinity Capture-MS), PDHA2 (Two-hybrid), PDHA2 (Affinity Capture-MS), PDHA2 (Affinity Capture-MS), PDHA2 (Co-purification), PDHA2 (Affinity Capture-MS), PDHA2 (Affinity Capture-MS), PDHA2 (Affinity Capture-MS), PDHA2 (Affinity Capture-MS)

ESM2 similar proteins: A0A2I2F2I5, A5A6L0, A7MB35, G0SHF3, O13366, O24457, P07342, P08559, P14874, P16387, P21839, P21953, P26267, P26268, P26284, P28838, P28839, P29803, P29804, P34385, P35486, P35487, P35738, P52899, P52900, P52901, P52902, P52903, Q06437, Q10489, Q2NL26, Q3ZC84, Q41768, Q41769, Q54C70, Q5R432, Q5R490, Q654V6, Q6K2E8, Q6P3A8

Diamond homologs: A5A6L0, A7MB35, G0SHF3, O13366, O24457, O31404, O66112, P08559, P09060, P16387, P21881, P26267, P26268, P26284, P27745, P29803, P29804, P35485, P35486, P35487, P37940, P51267, P52899, P52900, P52901, P52902, P52903, P60089, P60090, P9WIS2, P9WIS3, Q06437, Q10489, Q1RJX4, Q1XDM0, Q4MTG0, Q4UKQ6, Q54C70, Q5HGZ1, Q5R490

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
PDK4	down-regulates	PDHA2	phosphorylation
PDK1	down-regulates	PDHA2	phosphorylation
PDK2	down-regulates	PDHA2	phosphorylation
PDK3	down-regulates	PDHA2	phosphorylation
PDHA2	“form complex”	PDH	binding
ACAT1	“down-regulates activity”	PDHA2	acetylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	60
Likely benign	0
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
446251	NM_005390.5(PDHA2):c.679A>G (p.Met227Val)	Likely pathogenic

SpliceAI

219 predictions. Top by Δscore:

Variant	Effect	Δscore
4:95840436:G:GT	donor_gain	0.6000
4:95840184:C:T	donor_gain	0.5700
4:95840806:T:G	acceptor_gain	0.5700
4:95840810:TG:T	acceptor_gain	0.5600
4:95840811:G:GC	acceptor_gain	0.5400
4:95840808:TGTG:T	acceptor_gain	0.5000
4:95841154:A:T	donor_gain	0.5000
4:95841174:A:T	donor_gain	0.4900
4:95841072:G:GG	donor_gain	0.4800
4:95840810:T:TA	acceptor_gain	0.4600
4:95841087:G:T	donor_gain	0.4600
4:95841163:CTGAG:C	donor_loss	0.4600
4:95841164:TGAGG:T	donor_loss	0.4600
4:95841165:GAGG:G	donor_loss	0.4600
4:95841166:AGGTG:A	donor_loss	0.4600
4:95841167:GGTGA:G	donor_loss	0.4600
4:95841168:GTGA:G	donor_loss	0.4600
4:95841256:G:GG	donor_gain	0.4600
4:95840725:AT:A	acceptor_gain	0.4500
4:95840805:ATCT:A	acceptor_gain	0.4500
4:95841069:G:T	donor_gain	0.4500
4:95841169:T:A	donor_loss	0.4500
4:95841253:GCA:G	donor_gain	0.4500
4:95841255:A:AG	donor_gain	0.4500
4:95840813:GAA:G	donor_gain	0.4400
4:95841170:GAG:G	donor_loss	0.4400
4:95841069:G:GT	donor_gain	0.4300
4:95841069:GAA:G	donor_gain	0.4300
4:95841076:GAA:G	donor_gain	0.4300
4:95841153:G:GT	donor_gain	0.4300

AlphaMissense

2533 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:95840412:T:C	F88L	0.999
4:95840414:C:A	F88L	0.999
4:95840414:C:G	F88L	0.999
4:95840418:C:G	H90D	0.998
4:95840500:G:T	R117M	0.998
4:95841020:C:A	H290Q	0.998
4:95841020:C:G	H290Q	0.998
4:95841021:A:C	S291R	0.998
4:95841023:T:A	S291R	0.998
4:95841023:T:G	S291R	0.998
4:95840629:G:A	G160E	0.997
4:95840819:C:A	N223K	0.997
4:95840819:C:G	N223K	0.997
4:95841016:G:A	G289E	0.997
4:95841048:C:A	R300S	0.997
4:95841049:G:C	R300P	0.997
4:95840359:G:C	R70P	0.996
4:95840376:G:C	A76P	0.996
4:95840417:T:G	C89W	0.996
4:95840420:C:A	H90Q	0.996
4:95840420:C:G	H90Q	0.996
4:95840500:G:C	R117T	0.996
4:95840557:T:C	L136P	0.996
4:95840638:G:A	G163D	0.996
4:95840671:G:A	G174D	0.996
4:95840728:G:A	G193E	0.996
4:95840832:G:A	G228R	0.996
4:95840832:G:C	G228R	0.996
4:95840833:G:A	G228E	0.996
4:95841006:C:A	R286S	0.996

dbSNP variants (sampled 300 via entrez): RS1001688894 (4:95838999 C>A), RS1002249809 (4:95838184 T>C), RS1002858207 (4:95839613 G>T), RS1003299971 (4:95839313 A>C), RS1004212949 (4:95841427 C>A), RS1004263615 (4:95841679 A>G), RS1004549521 (4:95840153 G>T), RS1005051902 (4:95838698 T>C,G), RS1005074070 (4:95838980 T>C), RS1005740022 (4:95841435 G>A,C), RS1006225852 (4:95838796 G>C), RS1006643 (4:95839426 G>C,T), RS1006993839 (4:95839933 G>A,T), RS1007329414 (4:95838470 C>T), RS1009547278 (4:95838199 G>A)

Disease associations

OMIM: gene MIM:179061 | disease phenotypes: MIM:258150, MIM:619828

GenCC curated gene-disease

Disease	Classification	Inheritance
spermatogenic failure 70	Limited	Unknown

Mondo (3): spermatogenic failure 1 (MONDO:0009776), spermatogenic failure 70 (MONDO:0030733), azoospermia (MONDO:0100459)

Orphanet (0):

HPO phenotypes

12 total (12 of 12 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000027	Azoospermia
HP:0000118	Phenotypic abnormality
HP:0000798	Oligozoospermia
HP:0000837	Increased circulating gonadotropin level
HP:0003251	Male infertility
HP:0008669	Abnormal spermatogenesis
HP:0008734	Decreased testicular size
HP:0011462	Young adult onset
HP:0011961	Non-obstructive azoospermia
HP:0011962	Obstructive azoospermia
HP:0012207	Reduced sperm motility

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST008922_16	Triacylglyceride levels	4.000000e-08
GCST009144_27	Disease progression in age-related macular degeneration (adjusted for baseline)	6.000000e-06
GCST009391_899	Metabolite levels	5.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0008336	disease progression measurement
EFO:0010441	triacylglycerol 58:7 measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D053713	Azoospermia	C12.100.500.430.380; C12.100.750.700.380; C12.200.294.430.380
C562902	Oligosynaptic Infertility (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4500 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.33	Kd	4724	nM	CHEMBL5653589
5.33	ED50	4724	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148960: Binding affinity to human PDHA2 incubated for 45 mins by Kinobead based pull down assay	kd	4.7236	uM

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation	1
CGP 52608	affects binding, increases reaction	1
Benzo(a)pyrene	increases methylation	1
Mustard Gas	increases phosphorylation	1
Permethrin	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652002	Binding	Binding affinity to human PDHA2 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02307994	PHASE4	UNKNOWN	Clinical Research on Effectiveness and Safety of Treatment of Severe Oligospermia or Azoospermia With uFSH
NCT02275169	PHASE3	UNKNOWN	FSH Treatment for Non-obstructive Azoospermic Patients
NCT02544191	PHASE2	UNKNOWN	GnRHa Combined With hCG and hMG for Treatment of Patients With Non-obstructive Azoospermia
NCT03762967	PHASE2	UNKNOWN	Autologous Adipose-Derived Adult Stromal Vascular Cell Administration for Male Patients With Infertility
NCT02041910	PHASE1/PHASE2	UNKNOWN	Testicular Injection of Autologous Stem Cells for Treatment of Patients With Azoospermia
NCT00282477	Not specified	UNKNOWN	Trial to Evaluate Erectile Function, Fertility and Sperm Count in Male Cyclists Compared to Age Matched Controls
NCT00484081	Not specified	COMPLETED	Microdissection Testicular Sperm Extraction (MicroTESE) and IVF-ICSI Outcome in Non-Obstructive Azoospermia (NOA)
NCT00548977	Not specified	COMPLETED	Genetic Studies Spermatogenic Failure
NCT01375062	Not specified	COMPLETED	Obtaining Undifferentiated Cells From Testis Biopsy
NCT01509482	Not specified	COMPLETED	Insulin Resistance in Idiopathic Oligospermia and Azoospermia
NCT02008799	Not specified	UNKNOWN	Intra Testicular Artery Injection of Bone Marrow Stem Cell in Management of Azoospermia
NCT02339272	Not specified	COMPLETED	Study of Synapsis and Recombination in Male Meiosis and the Implications in Infertility
NCT02414295	Not specified	COMPLETED	Sperm Production in Kleinfelter Syndrome Patients After Mesenchymal Stem Cell Injection
NCT02418832	Not specified	RECRUITING	Testis Needle Aspiration of Sperm in Men With Azoospermia
NCT02617173	Not specified	UNKNOWN	The Effect of Low Electrical Current on Testicular Spermatocyte Count
NCT02773498	Not specified	TERMINATED	Comparison of Medical Results of Testicular Sperm Extraction by Conventional Surgery and Microsurgical Track
NCT03497728	Not specified	TERMINATED	Detection of Microdeletions in the Azoospermia Factor (AZF) Regions in Infertile Male Patients
NCT04675164	Not specified	COMPLETED	Laser Assisted Sperm Selection of Viable Immotile Testicular Sperm in Azoospermic Infertile Men
NCT05479474	Not specified	RECRUITING	Platelet Rich Plasma Testis Treatment for Infertile Men
NCT05628987	Not specified	RECRUITING	The Association of Gut Microbiota and Spermatogenic Dysfunction
NCT05866484	Not specified	COMPLETED	Testicular Sperm Aspiration (TESA) vs. Microfluidic Sperm Separation (MSS)
NCT06524258	Not specified	COMPLETED	Testicular Elastography for Microscopic Testicular Sperm Extraction
NCT06841328	Not specified	RECRUITING	Fertility Enhancement Through Regenerative Treatment in Ovaries and Testes
NCT06941922	Not specified	RECRUITING	Testicular Evaluation of Azoospermia Using Micro-Ultrasound
NCT07074015	Not specified	RECRUITING	IntelliWell: An AI-Assisted Imaging Platform for Detection and Location of Ultra-Rare Testicular Sperm in Surgical Specimens
NCT07357701	Not specified	RECRUITING	Identifying Genome Variants in Non-Obstructive Azoospermia (NOA) or Primary Ovarian Insufficiency (POI)
NCT07542626	Not specified	RECRUITING	Fertility Restoration With Autografting of Cryopreserved Immature Testicular Tissue