PDHB

Summary

PDHB (pyruvate dehydrogenase E1 subunit beta, HGNC:8808) is a protein-coding gene on chromosome 3p14.3, encoding Pyruvate dehydrogenase E1 component subunit beta, mitochondrial (P11177). Together with PDHA1 forms the heterotetrameric E1 subunit of the pyruvate dehydrogenase (PDH) complex.

The pyruvate dehydrogenase (PDH) complex is a nuclear-encoded mitochondrial multienzyme complex that catalyzes the overall conversion of pyruvate to acetyl-CoA and carbon dioxide, and provides the primary link between glycolysis and the tricarboxylic acid (TCA) cycle. The PDH complex is composed of multiple copies of three enzymatic components: pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2) and lipoamide dehydrogenase (E3). The E1 enzyme is a heterotetramer of two alpha and two beta subunits. This gene encodes the E1 beta subunit. Mutations in this gene are associated with pyruvate dehydrogenase E1-beta deficiency. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 5162 — RefSeq curated summary.

At a glance

• Gene–disease (curated): pyruvate dehydrogenase E1-beta deficiency (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 12
• Clinical variants (ClinVar): 400 total — 16 pathogenic, 20 likely-pathogenic (top 8% of genes corpus-wide)
• GTEx eGene: eQTL in 47 tissues, sQTL in 15 (q < 0.05)
• Phenotypes (HPO): 28
• Constraint (gnomAD): pLI 0.79 (intermediate), LOEUF 0.59 (moderately constrained)
• MANE Select transcript: NM_000925
• Interaction hub: 2,486 STRING partners (top 4% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8808
Approved symbol	PDHB
Name	pyruvate dehydrogenase E1 subunit beta
Location	3p14.3
Locus type	gene with protein product
Status	Approved
Aliases	PDHE1B, E1beta
Ensembl gene	ENSG00000168291
Ensembl biotype	protein_coding
OMIM	179060
Entrez	5162

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 17 protein_coding, 10 nonsense_mediated_decay, 5 retained_intron

MANE Select: ENST00000302746

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 4, TSL 3: 1, TSL 5: 2

ENST00000302746, ENST00000383714, ENST00000461692, ENST00000469364, ENST00000469827, ENST00000474765, ENST00000479945, ENST00000480626, ENST00000482894, ENST00000485460, ENST00000909150, ENST00000909152, ENST00000909153, ENST00000909154, ENST00000909155, ENST00000909156, ENST00000909157, ENST00000962538, ENST00000962539, ENST00000978823, ENST00001041297, ENST00001041298, ENST00001041299, ENST00001041300, ENST00001041302, ENST00001041303, ENST00001062180, ENST00001062182, ENST00001062183, ENST00001062184, ENST00001062186, ENST00001138545

RefSeq mRNA: 3 — MANE Select: NM_000925 NM_000925, NM_001173468, NM_001315536

CCDS: CCDS2890, CCDS54602, CCDS82795

Canonical transcript exons

ENST00000302746 — 10 exons

Exon	Start	End
ENSE00001835890	58427630	58428179
ENSE00001931564	58433768	58433832
ENSE00003484528	58430657	58430942
ENSE00003520071	58430128	58430238
ENSE00003562164	58428473	58428614
ENSE00003574534	58429708	58429799
ENSE00003579089	58431731	58431793
ENSE00003670871	58431877	58431984
ENSE00003672873	58431593	58431628
ENSE00003690105	58433631	58433684

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 99.46.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 73.8955 / max 1218.7888, expressed in 1826 samples.

Highest expression (Bgee): endothelial cell, heart right ventricle, biceps brachii, skeletal muscle tissue of rectus abdominis, skeletal muscle tissue of biceps brachii.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PDHB is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 47 tissues and its splicing (sQTL) in 15 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 62 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Muscle Skeletal	eqtl	5.0e-50	+0.26	3:58387440:G:C
Cells Cultured fibroblasts	eqtl	1.1e-42	+0.34	3:58384450:G:T
Artery Tibial	eqtl	9.0e-32	+0.29	3:58387158:T:C
Skin Sun Exposed Lower leg	eqtl	9.9e-26	+0.31	3:58384487:GT:G
Testis	eqtl	4.1e-23	+0.41	3:58449242:T:C
Brain Cortex	eqtl	5.1e-22	+0.52	3:58448437:A:G
Skin Not Sun Exposed Suprapubic	eqtl	6.8e-22	+0.30	3:58387440:G:C
Lung	eqtl	8.0e-20	+0.24	3:58372775:T:C
Whole Blood	eqtl	7.7e-19	+0.19	3:58399467:T:C
Colon Transverse	eqtl	2.6e-18	-0.28	3:58346769:C:T
Colon Sigmoid	eqtl	1.3e-16	+0.23	3:58397447:A:T
Nerve Tibial	eqtl	7.6e-16	+0.22	3:58469050:G:GAC
Brain Cerebellar Hemisphere	eqtl	9.6e-16	+0.29	3:58346781:C:T
Adipose Subcutaneous	eqtl	5.2e-14	+0.21	3:58384450:G:T
Esophagus Mucosa	eqtl	2.1e-13	-0.21	3:58355841:C:T
Brain Spinal cord cervical c-1	eqtl	6.6e-13	+0.30	3:58394738:A:T
Brain Frontal Cortex BA9	eqtl	1.1e-12	+0.35	3:58346781:C:T
Adipose Subcutaneous	sqtl	7.5e-12	-0.42	3:58399467:T:C
Pituitary	eqtl	8.9e-12	+0.24	3:58394738:A:T
Esophagus Muscularis	eqtl	1.2e-11	+0.15	3:58384450:G:T

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
42689	73.8955	1826

Top tissues by expression

showing 100 of 300 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	99.46	gold quality
heart right ventricle	UBERON:0002080	99.32	gold quality
biceps brachii	UBERON:0001507	98.85	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.71	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.70	gold quality
left ventricle myocardium	UBERON:0006566	98.69	gold quality
body of tongue	UBERON:0011876	98.61	gold quality
deltoid	UBERON:0001476	98.60	gold quality
myocardium	UBERON:0002349	98.52	gold quality
choroid plexus epithelium	UBERON:0003911	98.47	gold quality
vastus lateralis	UBERON:0001379	98.41	gold quality
tibialis anterior	UBERON:0001385	98.40	gold quality
quadriceps femoris	UBERON:0001377	98.36	gold quality
cardiac ventricle	UBERON:0002082	98.23	gold quality
adrenal tissue	UBERON:0018303	98.21	gold quality
heart left ventricle	UBERON:0002084	98.20	gold quality
triceps brachii	UBERON:0001509	98.13	gold quality
skeletal muscle tissue	UBERON:0001134	98.00	gold quality
muscle organ	UBERON:0001630	97.94	gold quality
skeletal muscle organ	UBERON:0014892	97.94	gold quality
gastrocnemius	UBERON:0001388	97.84	gold quality
muscle tissue	UBERON:0002385	97.83	gold quality
muscle of leg	UBERON:0001383	97.82	gold quality
heart	UBERON:0000948	97.79	gold quality
gluteal muscle	UBERON:0002000	97.77	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.77	gold quality
diaphragm	UBERON:0001103	97.74	gold quality
apex of heart	UBERON:0002098	97.74	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	97.73	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.69	gold quality
upper leg skin	UBERON:0004262	97.64	gold quality
cardiac atrium	UBERON:0002081	97.56	gold quality
right atrium auricular region	UBERON:0006631	97.52	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.47	gold quality
tongue	UBERON:0001723	97.43	gold quality
right adrenal gland	UBERON:0001233	97.41	gold quality
vena cava	UBERON:0004087	97.41	gold quality
right adrenal gland cortex	UBERON:0035827	97.35	gold quality
pons	UBERON:0000988	97.34	gold quality
renal medulla	UBERON:0000362	97.28	gold quality
colonic mucosa	UBERON:0000317	97.18	gold quality
nephron tubule	UBERON:0001231	97.12	gold quality
skin of hip	UBERON:0001554	96.84	gold quality
left adrenal gland	UBERON:0001234	96.80	gold quality
adrenal cortex	UBERON:0001235	96.72	gold quality
mammalian vulva	UBERON:0000997	96.70	gold quality
lower esophagus	UBERON:0013473	96.70	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.70	gold quality
renal glomerulus	UBERON:0000074	96.67	gold quality
gingiva	UBERON:0001828	96.67	gold quality
parotid gland	UBERON:0001831	96.64	gold quality
pharyngeal mucosa	UBERON:0000355	96.63	gold quality
gingival epithelium	UBERON:0001949	96.62	gold quality
postcentral gyrus	UBERON:0002581	96.62	gold quality
adrenal gland	UBERON:0002369	96.59	gold quality
left adrenal gland cortex	UBERON:0035825	96.58	gold quality
cervix squamous epithelium	UBERON:0006922	96.57	gold quality
metanephric glomerulus	UBERON:0004736	96.55	gold quality
kidney epithelium	UBERON:0004819	96.55	gold quality
entorhinal cortex	UBERON:0002728	96.54	gold quality
metanephros	UBERON:0000081	96.47	gold quality
epithelium of nasopharynx	UBERON:0001951	96.45	gold quality
esophagus squamous epithelium	UBERON:0006920	96.44	gold quality
nasopharynx	UBERON:0001728	96.43	gold quality
squamous epithelium	UBERON:0006914	96.42	gold quality
kidney	UBERON:0002113	96.41	gold quality
superior surface of tongue	UBERON:0007371	96.41	gold quality
germinal epithelium of ovary	UBERON:0001304	96.39	gold quality
superior frontal gyrus	UBERON:0002661	96.37	gold quality
prefrontal cortex	UBERON:0000451	96.36	gold quality
rectum	UBERON:0001052	96.36	gold quality
adult mammalian kidney	UBERON:0000082	96.31	gold quality
pigmented layer of retina	UBERON:0001782	96.31	gold quality
parietal lobe	UBERON:0001872	96.31	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.30	gold quality
retina	UBERON:0000966	96.28	gold quality
middle temporal gyrus	UBERON:0002771	96.26	gold quality
epithelium of esophagus	UBERON:0001976	96.13	gold quality
parietal pleura	UBERON:0002400	96.12	gold quality
cortex of kidney	UBERON:0001225	96.07	gold quality
islet of Langerhans	UBERON:0000006	96.03	gold quality
smooth muscle tissue	UBERON:0001135	96.01	gold quality
adult organism	UBERON:0007023	96.00	gold quality
bronchial epithelial cell	CL:0002328	95.98	gold quality
left coronary artery	UBERON:0001626	95.97	gold quality
sigmoid colon	UBERON:0001159	95.94	gold quality
superior vestibular nucleus	UBERON:0007227	95.93	gold quality
cardia of stomach	UBERON:0001162	95.88	gold quality
penis	UBERON:0000989	95.86	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.86	gold quality
Brodmann (1909) area 46	UBERON:0006483	95.85	gold quality
esophagus	UBERON:0001043	95.82	gold quality
popliteal artery	UBERON:0002250	95.77	gold quality
tibial artery	UBERON:0007610	95.77	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.77	gold quality
eye	UBERON:0000970	95.76	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.74	gold quality
coronary artery	UBERON:0001621	95.71	gold quality
right coronary artery	UBERON:0001625	95.71	gold quality
Ammon’s horn	UBERON:0001954	95.69	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 78 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Tongue	tissue	279.4
Skeletal muscle	tissue	255.4	medium
Heart muscle	tissue	163.8	high
Caudate putamen	tissue	163.2
Frontal cortex	tissue	161.2
Liver	tissue	103.5	not detected
Kidney	tissue	94.1	high
Parathyroid gland	tissue	83.4	high
Choroid plexus	tissue	61.6
Adrenal gland	tissue	61.4	medium
Smooth muscle	tissue	59.6	medium
Rectum	tissue	56.7	medium
Adipose tissue	tissue	56.2	medium
Thalamus	tissue	54.0
Esophagus	tissue	53.9	medium
Placenta	tissue	53.5	medium
Pons	tissue	53.4
Colon	tissue	53.3	high
Superior colliculi	tissue	53.2
Tonsil	tissue	52.5	medium
Medulla oblongata	tissue	50.3
Lymph node	tissue	49.6	medium
Thymus	tissue	49.5
Seminal vesicle	tissue	49.1	high
Cerebral cortex	tissue	48.7	medium
Somatosensory cortex	tissue	48.7
Stomach 1	tissue	48.0	high
Midbrain	tissue	48.0
Spinal cord	tissue	47.6
Urinary bladder	tissue	46.5	medium
Prostate	tissue	45.5	medium
Substantia nigra	tissue	44.1
Hippocampal formation	tissue	43.7
Pituitary gland	tissue	43.3
Salivary gland	tissue	43.3	medium
Occipital cortex	tissue	42.3
Epididymis	tissue	42.2	medium
Hypothalamus	tissue	41.1
Putamen	tissue	41.0
Septum	tissue	40.8
Cervix	tissue	40.7	low
Periaqueductal gray	tissue	40.6
Spleen	tissue	40.4	medium
Breast	tissue	40.2	medium
Ovary	tissue	40.0	not detected
Duodenum	tissue	40.0	medium
Motor cortex	tissue	39.9
Appendix	tissue	39.9	medium
Testis	tissue	39.6	medium
Cerebellum	tissue	38.8	high
Thyroid gland	tissue	38.2	medium
Ventral forebrain	tissue	37.8
Corpus callosum	tissue	37.4
Prefrontal cortex	tissue	37.2
Retrosplenial and cingulate cortex	tissue	36.5
Postcentral gyrus	tissue	36.2
Entorhinal cortex	tissue	36.1
Temporal cortex	tissue	35.9
Fallopian tube	tissue	35.4	low
Basal ganglia	tissue	34.9	medium

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Blood vessel (58.2), Ventral spinal cord (47.6), Dorsal hippocampus (43.7), Dorsal spinal cord (43.6), Lateral funiculus (white matter) (41.1).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting PDHB by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 38 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4775	99.98	75.00	6394
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-3606-3P	99.11	69.84	3254
HSA-MIR-194-5P	99.01	69.65	1465
HSA-MIR-942-3P	98.81	69.04	876
HSA-MIR-6893-3P	97.79	64.91	1238

Functional genomics

gnomAD constraint: pLI 0.787, LOEUF 0.586, missense Z 2.22 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000302746 splits into 3 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
3:58,428,037–58,430,857	208 / 285.0	0.73	no
3:58,430,858–58,433,633	56 / 124.2	0.45	no
3:58,433,634–58,433,809	58 / 42.1	1.38	no

Literature-anchored findings (GeneRIF, showing 10)

• Data indicate that PDH deficiency in our patient involves a post-translational modification in which EGFR-PTK-mediated tyrosine phosphorylation of the E1beta protein leads to enhanced ubiquitination followed by proteasome-mediated degradation. (PMID:17923481)
• clinical findings are similar to those of PDHA1 deficiency, except that ataxia was more frequent in PDHA1 cases and consanguinity was found only in PDHB families. (PMID:18164639)
• Species specificity in the interaction between hE1beta and hE2 in pyruvate dehydrogenase complex. (PMID:18206651)
• Sequencing of PDHB reveals a homozygous point mutation (c.302T>C), causing a predicted amino acid change in patient 1. Patient 2 is compound heterozygote for mutations c.301A>G (p.M101V) and c.313G>A (p.R105Q). (PMID:19924563)
• PHD3 depletion did not affect the expression of the PDH-E1alpha, E1beta, and E2 subunits, or the phosphorylation status of E1alpha, but destabilized the PDH complex (PDC), resulting in less functional PDC. (PMID:25088999)
• Data indicate that (pro)renin receptor ATP6PA2 interacts with the E1 beta subunit of pyruvate dehydrogenase and controlling its protein stability (PMID:25720494)
• PDHB was downregulated in nasopharyngeal carcinoma cells. Forced expression of PDHB in NPC cells inhibited cell growth and migration, while knocking down the expression of PDHB promoted the growth, migration, and tumorigenesis of NPC cells. PDHB inhibited ERK signaling and cell growth driven by RasV12. (PMID:26857147)
• Building on evidence that PDH activity depends on the stability of a multi-protein PDH complex, the authors found that the PDH-E1beta subunit of the PDH complex is downregulated to inhibit PDH activity under conditions of prolonged hypoxia which establishs the specific mechanism through which PDH acts as an oncogenic factor by tuning glycolytic metabolism in cancer cells. (PMID:29436427)
• Pyruvate dehydrogenase B regulates myogenic differentiation via the FoxP1-Arih2 axis. (PMID:36564038)
• Integrated single-cell and bulk characterization of cuproptosis key regulator PDHB and association with tumor microenvironment infiltration in clear cell renal cell carcinoma. (PMID:37350959)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pdhb	ENSDARG00000021346
mus_musculus	Pdhb	ENSMUSG00000021748
rattus_norvegicus	Pdhb	ENSRNOG00000007895
drosophila_melanogaster	Pdhb	FBGN0039635
caenorhabditis_elegans		WBGENE00015413

Paralogs (4): TKTL1 (ENSG00000007350), BCKDHB (ENSG00000083123), TKTL2 (ENSG00000151005), TKT (ENSG00000163931)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1915513) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 11 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal somite shape	1
abnormal embryo size	1
abnormal embryo turning	1
abnormal neural tube morphology	1
abnormal pharyngeal arch morphology	1
abnormal forebrain development	1
embryonic growth retardation	1
abnormal retina blood vessel morphology	1
preweaning lethality, complete penetrance	1
preweaning lethality, incomplete penetrance	1
embryonic lethality prior to tooth bud stage	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Staphylococcus aureus subsp. aureus Mu50	P0A0A1	100.0%	Diamond
Staphylococcus aureus subsp. aureus MW2	P0A0A2	100.0%	Diamond
Staphylococcus aureus	P0A0A3	100.0%	Diamond
Staphylococcus aureus subsp. aureus N315	P99063	100.0%	Diamond
Mycobacterium tuberculosis CDC1551	P9WIS0	100.0%	Diamond
Mycobacterium tuberculosis H37Rv	P9WIS1	100.0%	Diamond
Staphylococcus epidermidis RP62A	Q5HQ75	100.0%	Diamond
Staphylococcus aureus subsp. aureus MSSA476	Q6GAC0	100.0%	Diamond
Staphylococcus aureus subsp. aureus MRSA252	Q6GHZ1	100.0%	Diamond
Staphylococcus epidermidis ATCC 12228	Q8CPN2	100.0%	Diamond
Staphylococcus aureus subsp. aureus COL	Q5HGZ0	99.7%	Diamond
Pongo abelii	Q5RE79	99.7%	Diamond
Thermus thermophilus HB8	Q5SLR3	99.7%	Diamond
Thermus thermophilus HB27	Q72GU2	99.7%	Diamond
Rickettsia typhi str. Wilmington	Q68XA8	98.8%	Diamond
Rickettsia prowazekii str. Madrid E	Q9ZDR3	98.8%	Diamond
Mesocricetus auratus	P86222	96.9%	Diamond
Rickettsia felis Marseille-URRWFXCal2	Q4UKQ7	96.0%	Diamond
Rickettsia conorii str. Malish 7	Q92IS2	96.0%	Diamond
Oryza sativa Japonica Group	Q10G39	95.3%	Diamond
Bos taurus	P11966	94.2%	Diamond
Arabidopsis thaliana	O64688	91.7%	Diamond
Porphyra purpurea	P51266	91.5%	Diamond
Pyropia yezoensis	Q1XDM1	91.5%	Diamond
Rickettsia bellii RML369-C	Q1RJX3	91.0%	Diamond
Zygnema circumcarinatum	Q32RM2	89.2%	Diamond
Staurastrum punctulatum	Q32RS0	89.2%	Diamond
Mycoplasmoides genitalium G37	P47515	89.0%	Diamond
Mycoplasmoides pneumoniae M129	P75391	89.0%	Diamond
Pseudomonas putida	P09061	88.1%	Diamond
Pseudomonas aeruginosa PAO1	Q9I1M1	88.1%	Diamond
Chaetosphaeridium globosum	Q8MA03	87.7%	Diamond
Geobacillus stearothermophilus	P21874	86.8%	Diamond
Bacillus subtilis subsp. subtilis str. 168	P21882	86.8%	Diamond
Lathyrus oleraceus	P52904	83.4%	Diamond
Gracilaria tenuistipitata var. liui	Q6B8T1	83.0%	Diamond
Chlorokybus atmophyticus	A2CI50	82.5%	Diamond
Mesostigma viride	Q9MUR4	82.5%	Diamond
Chara vulgaris	Q1ACL0	80.1%	Diamond
Sinorhizobium meliloti 1021	Q9R9N4	76.8%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
FAM3D-AS1	ncRNA	105377108
FAM107A	protein-coding	11170
FAM3D	protein-coding	131177
KCTD6	protein-coding	200845
ACOX2	protein-coding	8309
HTD2	protein-coding	109703458
RPP14	protein-coding	11102
PXK	protein-coding	54899
ABHD6	protein-coding	57406

Protein

Protein identifiers

Pyruvate dehydrogenase E1 component subunit beta, mitochondrial — P11177 (reviewed: P11177)

All UniProt accessions (4): P11177, A0A384MDR8, C9J634, F8WF02

UniProt curated annotations — full annotation on UniProt →

Function. Together with PDHA1 forms the heterotetrameric E1 subunit of the pyruvate dehydrogenase (PDH) complex. 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 PDHA1 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. Interacts with DLAT.

Subcellular location. Mitochondrion matrix.

Disease relevance. Pyruvate dehydrogenase E1-beta deficiency (PDHBD) [MIM:614111] An enzymatic defect causing primary lactic acidosis in children. It is associated with a broad clinical spectrum ranging from fatal lactic acidosis in the newborn to chronic neurologic dysfunction with structural abnormalities in the central nervous system without systemic acidosis. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (3)

UniProt ID	Names	Canonical?
P11177-1	1	yes
P11177-2	2
P11177-3	3

RefSeq proteins (3): NP_000916, NP_001166939, NP_001302465 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005475	Transketolase-like_Pyr-bd	Domain
IPR009014	Transketo_C/PFOR_II	Homologous_superfamily
IPR027110	PDHB_mito-type	Family
IPR029061	THDP-binding	Homologous_superfamily
IPR033248	Transketolase_C	Domain

Pfam: PF02779, PF02780

Enzyme classification (BRENDA)

• EC 1.2.1.104 — pyruvate dehydrogenase system (BRENDA: 46 organisms, 32 substrates, 100 inhibitors, 83 Km, 12 kcat entries)
• EC 1.2.4.1 — pyruvate dehydrogenase (acetyl-transferring) (BRENDA: 29 organisms, 58 substrates, 114 inhibitors, 56 Km, 45 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
PYRUVATE	0.0002–1	44
PYRUVATE	0.0011–1.7	32
NAD+	0.01–0.27	14
THIAMINE DIPHOSPHATE	0.0006–0.065	14
COA	0.0005–0.61	12
THIAMINE DIPHOSPHATE	0.0016–0.05	3
LIPOYL DOMAIN	0.024–0.027	2
2-OXOBUTANOATE	1.35	1
2-OXOBUTYRATE	1.66	1
2-OXOISOVALERATE	1.27	1
COENZYME A	0.003	1
HYDROXYETHYL THIAMINE DIPHOSPHATE	0.0082	1
LIPOYL DOMAIN	0.02	1
N-ACETYL-GDLLAEIETDK(LIPOYL)-ATIG-AMIDE	15	1
N-TERMINAL LIPOYL DOMAIN	0.052	1

Catalyzed reactions (Rhea)

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

UniProt features (65 total): helix 18, strand 15, mutagenesis site 7, binding site 6, turn 5, sequence conflict 4, sequence variant 3, modified residue 2, splice variant 2, transit peptide 1, chain 1, site 1

Structure

Experimental structures (PDB)

9 structures by resolution:

PDB	Title	Method	Resolution (Å)
2OZL	Human pyruvate dehydrogenase S264E variant	X-RAY DIFFRACTION	1.9
1NI4	HUMAN PYRUVATE DEHYDROGENASE	X-RAY DIFFRACTION	1.95
3EXE	Crystal structure of the pyruvate dehydrogenase (E1p) component of human pyruvate …	X-RAY DIFFRACTION	1.98
3EXI	Crystal structure of the pyruvate dehydrogenase (E1p) component of human pyruvate …	X-RAY DIFFRACTION	2.2
3EXH	Crystal structure of the pyruvate dehydrogenase (E1p) component of human pyruvate …	X-RAY DIFFRACTION	2.44
6CER	Human pyruvate dehydrogenase complex E1 component V138M mutation	X-RAY DIFFRACTION	2.69
6CFO	HUMAN PYRUVATE DEHYDROGENASE E1 COMPONENT COMPLEX WITH COVALENT TDP ADDUCT ACETYL …	X-RAY DIFFRACTION	2.7
3EXF	Crystal structure of the pyruvate dehydrogenase (E1p) component of human pyruvate …	X-RAY DIFFRACTION	3
3EXG	Crystal structure of the pyruvate dehydrogenase (E1p) component of human pyruvate …	X-RAY DIFFRACTION	3.01

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P11177-F1	94.18	0.91

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Oxidoreductases, Metabolic proteins, Predicted intracellular proteins, Citric acid cycle related proteins, Disease related genes, Potential drug targets, Human disease related genes, Congenital disorders of metabolism, Congenital disorders of carbohydrate metabolism

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): mitochondria; cell junctions; nucleoplasm

Antibody reliability (HPA): IH enhanced · IF supported

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 (1)

Position	Role
319	important for interaction with dlat

Ligand- & substrate-binding residues (6)

Position	Role
89	thiamine diphosphate
142	K(+)
190	K(+)
191	K(+)
193	K(+)
195	K(+)

Post-translational modifications (2)

Type	Positions
N6-acetyllysine	354
Phosphotyrosine	67

Mutagenesis-validated functional residues (7)

Position	Phenotype
259	does not affect interaction with dlat.
262	does not affect interaction with dlat.
264	does not affect interaction with dlat.
319	inhibits interaction with dlat. does not affect pyruvate decarboxylase activity. loss of multienzyme pyruvate dehydrogenase complex …
319	reduces interaction with dlat. reduces multienzyme pyruvate dehydrogenase complex activity. does not affect pyruvate decarboxylase activity.
359	reduces pyruvate decarboxylase and multienzyme pyruvate dehydrogenase complex activity. does not affect interaction with dlat.

Function

Pathways and Gene Ontology

Reactome pathways

4 curated (TAS) of 11; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

11 pathways:

ID	Pathway	Evidence
R-HSA-9837999	Mitochondrial protein degradation	curated
R-HSA-9861559	PDH complex synthesizes acetyl-CoA from PYR	curated
R-HSA-204174	Regulation of pyruvate dehydrogenase (PDH) complex	curated
R-HSA-5362517	Signaling by Retinoic Acid	curated
R-HSA-1428517	Aerobic respiration and respiratory electron transport	—
R-HSA-1430728	Metabolism	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-70268	Pyruvate metabolism	—
R-HSA-9861718	Regulation of pyruvate metabolism	—
R-HSA-162582	Signal Transduction	—
R-HSA-9006931	Signaling by Nuclear Receptors	—

MSigDB gene sets: 220 (showing top): STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, MORF_HDAC1, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, MORF_HDAC2, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, KEGG_GLYCOLYSIS_GLUCONEOGENESIS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ACETYL_COA_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_SULFUR_COMPOUND_BIOSYNTHETIC_PROCESS, WATANABE_RECTAL_CANCER_RADIOTHERAPY_RESPONSIVE_UP, GOBP_AMIDE_METABOLIC_PROCESS

GO Biological Process (6): glucose metabolic process (GO:0006006), pyruvate decarboxylation to acetyl-CoA (GO:0006086), tricarboxylic acid cycle (GO:0006099), aerobic respiration (GO:0009060), sulfur compound biosynthetic process (GO:0044272), purine-containing compound biosynthetic process (GO:0072522)

GO Molecular Function (4): pyruvate dehydrogenase (acetyl-transferring) activity (GO:0004739), metal ion binding (GO:0046872), protein binding (GO:0005515), oxidoreductase activity (GO:0016491)

GO Cellular Component (4): nucleus (GO:0005634), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), pyruvate dehydrogenase complex (GO:0045254)

Reactome top-level categories

7 top-level categories:

Category	Pathways
Pyruvate metabolism	2
Regulation of pyruvate metabolism	1
Signaling by Nuclear Receptors	1
Metabolism of proteins	1
Metabolism	1
Aerobic respiration and respiratory electron transport	1
Signal Transduction	1

GO top-level categories

22 GO namespaces:

Category	Terms
aerobic respiration	2
biosynthetic process	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
cellular respiration	1
sulfur compound metabolic process	1
purine-containing compound 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
cytoplasm	1
mitochondrion	1
intracellular organelle lumen	1
alpha-ketoacid dehydrogenase complex	1
acetyltransferase complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 5 of 14 annotations. The rest are phylogenetic / computational / electronic (IEA).

5 experimentally-supported GO terms:

GO term	NS	Evidence
pyruvate decarboxylation to acetyl-CoA	BP	direct assay
mitochondrion	CC	direct assay
nucleus	CC	high-throughput assay
pyruvate dehydrogenase complex	CC	direct assay
pyruvate dehydrogenase (acetyl-transferring) activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 2,486 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PDHB	PDHA1	P08559	989
PDHB	DLAT	P10515	977
PDHB	PDHX	O00330	973
PDHB	LIPT1	Q9Y234	895
PDHB	LIAS	O43766	889
PDHB	PDP2	Q9P2J9	886
PDHB	DLD	P09622	877
PDHB	FDX1	P10109	857
PDHB	PDHA2	P29803	826
PDHB	PDP1	Q9P0J1	810
PDHB	GCSH	P23434	757
PDHB	SLC31A1	O15431	745
PDHB	LIPT2	A6NK58	722
PDHB	GLS	O94925	720
PDHB	GLS2	Q9UI32	719

IntAct

Human interaction partners of PDHB in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

25 partners by confidence:

Partner	Interaction type	MIscore	Records
PDHA1	direct interaction	0.690	1
DLAT	direct interaction	0.670	7
SHANK3	physical association	0.550	1
DLD	association	0.530	1
DUSP29	association	0.420	2
ADORA2A	physical association	0.370	1
AKT1	physical association	0.370	1
ANXA7	physical association	0.370	1
CDKN1A	physical association	0.370	1
FCER1A	physical association	0.370	1
GNB2	physical association	0.370	1
GRB7	physical association	0.370	1
ITGB1	physical association	0.370	1
PFDN1	physical association	0.370	1
RAP1B	physical association	0.370	1
RCC1	physical association	0.370	1
TSC22D1	physical association	0.370	1
PDHX	association	0.350	1
BRF2	physical association	0.000	1
CFAP20	physical association	0.000	1
GH1	physical association	0.000	1
IKBKE	physical association	0.000	1
MCC	physical association	0.000	1
RBM11	physical association	0.000	1
WRAP73	physical association	0.000	1

BioGRID (440 interactions; top human partners by supporting records): PDHA1 (Affinity Capture-MS; 11 records), DLAT (Affinity Capture-MS; 8 records), PDHX (Affinity Capture-MS; 6 records), DLD (Affinity Capture-MS; 5 records), PDK1 (Affinity Capture-MS; 4 records), PPP3CA (Affinity Capture-MS; 4 records), BANP (Affinity Capture-MS; 3 records), DUPD1 (Affinity Capture-MS; 3 records), FHL2 (Affinity Capture-MS; 3 records), PDK2 (Affinity Capture-MS; 3 records), PDK3 (Affinity Capture-MS; 3 records), PPP3CB (Affinity Capture-MS; 3 records), PPP3CC (Affinity Capture-MS; 3 records), PPP3R1 (Affinity Capture-MS; 3 records), STAT5A (Affinity Capture-MS; 3 records)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
PDHB	“form complex”	PDH	binding

Disease & clinical

Genetic variants

Variant evidence for PDHB: 400 ClinVar records (36 pathogenic / likely pathogenic); 12 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	16
Likely pathogenic	20
Uncertain significance	96
Likely benign	215
Benign	24

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 36 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
839569	NM_000925.4(PDHB):c.301A>G (p.Met101Val)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
2677597	NM_000925.4(PDHB):c.352C>T (p.Gln118Ter)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
2677599	NM_000925.4(PDHB):c.934+1G>A	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
217513	NM_000925.4(PDHB):c.300_303+7del	Pathogenic	criteria provided, single submitter	1
2501782	NM_000925.4(PDHB):c.1A>G (p.Met1Val)	Pathogenic	criteria provided, single submitter	1
2760571	NM_000925.4(PDHB):c.714dup (p.Val239fs)	Pathogenic	criteria provided, single submitter	1
2799883	NM_000925.4(PDHB):c.495G>A (p.Trp165Ter)	Pathogenic	criteria provided, single submitter	1
2834403	NM_000925.4(PDHB):c.803del (p.Met268fs)	Pathogenic	criteria provided, single submitter	1
2853430	NM_000925.4(PDHB):c.231T>G (p.Tyr77Ter)	Pathogenic	criteria provided, single submitter	1
2859779	NM_000925.4(PDHB):c.639_655del (p.Pro214fs)	Pathogenic	criteria provided, single submitter	1
2961156	NM_000925.4(PDHB):c.478_479del (p.Gln160fs)	Pathogenic	criteria provided, single submitter	1
3003908	NM_000925.4(PDHB):c.533_534delinsAA (p.Trp178Ter)	Pathogenic	criteria provided, single submitter	1
3014800	NM_000925.4(PDHB):c.578del (p.Asp193fs)	Pathogenic	criteria provided, single submitter	1
4721142	NM_000925.4(PDHB):c.650dup (p.Ser218fs)	Pathogenic	criteria provided, single submitter	1
4725125	NM_000925.4(PDHB):c.461dup (p.Ala155fs)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore PDHB’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 28 predictions of 534):

Position(s)	Effect	Δscore	Sites
3:58428475	donor_gain	1.0000
3:58429706–58429707	donor_loss	1.0000	3
3:58430126–58430127	donor_loss	1.0000	4
3:58430131	donor_gain	1.0000
3:58430239–58430240	acceptor_loss	1.0000	4
3:58430248	acceptor_gain	1.0000
3:58431875–58431876	donor_loss	1.0000	4
3:58431985–58431986	acceptor_loss	1.0000	6
3:58431996	acceptor_gain	1.0000
3:58433629–58433630	donor_loss	1.0000	3

AlphaMissense

1,299 missense substitutions predicted likely pathogenic (of 2,344 scored), across 288 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M111	9	0.991	1.000
M133	9	0.959	0.995
H158	8	0.998	0.999
D84	8	0.996	0.999
F115	8	0.996	1.000
D121	8	0.995	0.999
D182	8	0.983	0.996
F92	8	0.976	0.999
F144	8	0.971	0.999
N125	8	0.953	0.999
F110	8	0.951	0.998
N114	8	0.934	1.000
D275	8	0.925	0.975
D329	8	0.874	0.969
D193	8	0.819	0.942
E58	7	0.998	0.999
E59	7	0.998	1.000
E89	7	0.997	0.999
E203	7	0.993	0.997
E201	7	0.991	0.998

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	5.19e-07
Kidney Renal Papillary Cell Carcinoma (TCGA)	favorable	0.000152

Disease associations

OMIM: gene MIM:179060 | disease phenotypes: MIM:614111, MIM:608782

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
pyruvate dehydrogenase E1-beta deficiency	Definitive	Autosomal recessive	6

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
Leigh syndrome	Moderate	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (11 panels, 11 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

11 panels:

Panel	Rating
Fetal anomalies	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Likely inborn error of metabolism	green
Mitochondrial disorders	green
Paediatric disorders	green
Possible mitochondrial disorder, nuclear genes	green
Pyruvate dehydrogenase (PDH) deficiency	green
Undiagnosed metabolic disorders	green
Unexplained death in infancy and sudden unexplained death in childhood	green

Mondo (2): pyruvate dehydrogenase E1-beta deficiency (MONDO:0013580), pyruvate dehydrogenase phosphatase deficiency (MONDO:0012120)

Orphanet (3): Pyruvate dehydrogenase E1-beta deficiency (Orphanet:255138), Pyruvate dehydrogenase deficiency (Orphanet:765), Pyruvate dehydrogenase phosphatase deficiency (Orphanet:79246)

HPO phenotypes

28 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001274	Agenesis of corpus callosum
HP:0001290	Generalized hypotonia
HP:0001302	Pachygyria
HP:0001315	Diminished deep tendon reflex
HP:0001321	Cerebellar hypoplasia
HP:0001511	Intrauterine growth retardation
HP:0001987	Hyperammonemia
HP:0001999	Abnormal facial shape
HP:0002079	Hypoplasia of the corpus callosum
HP:0002119	Ventriculomegaly
HP:0002365	Hypoplasia of the brainstem
HP:0002683	Abnormal calvaria morphology
HP:0002928	Decreased activity of the pyruvate dehydrogenase complex
HP:0003128	Lactic acidosis
HP:0004325	Decreased body weight
HP:0006970	Periventricular leukomalacia
HP:0007016	Corticospinal tract hypoplasia
HP:0007109	Periventricular cysts
HP:0007165	Periventricular heterotopia
HP:0007772	Impaired smooth pursuit
HP:0012758	Neurodevelopmental delay
HP:0200012	Short corpus callosum

GWAS associations

12 associations:

Study	Trait	p-value
GCST003155_43	Systemic lupus erythematosus	3e-14
GCST010002_426	Refractive error	5e-14
GCST010245_229	LDL cholesterol levels	7e-14
GCST010243_60	Apolipoprotein B levels	3e-12
GCST007446_8	vWF levels	5e-9
GCST007446_51	vWF levels	6e-9
GCST007446_52	vWF levels	9e-9
GCST005752_45	Systemic lupus erythematosus	2e-8
GCST007446_7	vWF levels	3e-8
GCST008570_5	Composite immunoglobulin trait (IgA x IgG/IgM)	3e-8
GCST008576_6	IgG levels	7e-7
GCST006197_6	Type 1 diabetes autoantibodies in high risk HLA genotype individuals (time to event)	9e-6

EFO canonical traits (from GWAS)

4 canonical traits:

EFO ID	Trait name
EFO:0000482	event free survival time
EFO:0004866	autoantibody measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004611	low density lipoprotein cholesterol measurement

MeSH disease descriptors

2 disease descriptors:

Descriptor	Name	Tree numbers
C566729	Pyruvate Dehydrogenase E1-Beta Deficiency *(supp.)*
C536258	Pyruvate dehydrogenase phosphatase deficiency *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4882 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (2 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.53	Kd	2944	nM	CHEMBL3752910
5.48	ED50	3326	nM	CHEMBL3752910
5.20	Kd	6356	nM	CHEMBL5653589
5.14	ED50	7182	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 6 total; 2 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-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148961: Binding affinity to human PDHB incubated for 45 mins by Kinobead based pull down assay	kd	2.9436	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148961: Binding affinity to human PDHB incubated for 45 mins by Kinobead based pull down assay	kd	6.3559	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	3
sodium arsenite	increases expression, affects expression, decreases expression	3
Tobacco Smoke Pollution	decreases expression	2
Valproic Acid	affects expression, decreases expression	2
Cyclosporine	decreases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
sodium arsenate	decreases expression	1
ferric ammonium citrate	decreases reaction, increases expression	1
arsenite	increases reaction, affects binding	1
cobaltous chloride	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
azaspiracid	increases expression	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
UCF 101	increases expression	1
2-amino-14,16-dimethyloctadecan-3-ol	decreases expression	1
tetraarsenic tetrasulfide	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Imatinib Mesylate	affects cotreatment, decreases expression	1
Zoledronic Acid	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Ethanol	decreases expression, increases abundance, affects cotreatment	1
Cadmium	increases abundance, increases expression	1
Deferoxamine	increases expression, decreases reaction	1
Dimethyl Sulfoxide	increases expression	1
Dinitrochlorobenzene	affects binding	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118619	Binding	Binding affinity to PDHB in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — *Bioorg Med Chem*

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1PM	Abcam K-562 PDHB KO	Cancer cell line	Female
CVCL_D2L8	Abcam Raji PDHB KO	Cancer cell line	Male
CVCL_WQ23	Abcam Jurkat PDHB KO	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

5 trials:

NCT	Phase	Status	Title
NCT02616484	Phase 3	ACTIVE_NOT_RECRUITING	Trial of Dichloroacetate in Pyruvate Dehydrogenase Complex Deficiency:
NCT03734263	Phase 2	COMPLETED	Use of Phenylbutyrate Therapy for Patients With Pyruvate Dehydrogenase Complex Deficiency.
NCT06340685	Phase 1	RECRUITING	Triheptanoin for Children With Primary-Specific Pyruvate Dehydrogenase Complex (PDC) Deficiency
NCT05257005	Not specified	UNKNOWN	Natural History Study of Pyruvate Dehydrogenase Deficiency
NCT06931262	Not specified	AVAILABLE	Expanded Access Treatment Protocol With DCA for Patients With PDCD

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for PDHB across ~30M SureChEMBL compounds — explore on Sugi Predict.