PDP1

Summary

PDP1 (pyruvate dehydrogenase phosphatase catalytic subunit 1, HGNC:9279) is a protein-coding gene on chromosome 8q22.1, encoding [Pyruvate dehydrogenase [acetyl-transferring]]-phosphatase 1, mitochondrial (Q9P0J1). Mitochondrial enzyme that catalyzes the dephosphorylation and concomitant reactivation of the alpha subunit of the E1 component of the pyruvate dehydrogenase complex (PDC), thereby stimulating the conversion of pyruvate into acetyl-CoA.

Pyruvate dehydrogenase (E1) is one of the three components (E1, E2, and E3) of the large pyruvate dehydrogenase complex. Pyruvate dehydrogenase kinases catalyze phosphorylation of serine residues of E1 to inactivate the E1 component and inhibit the complex. Pyruvate dehydrogenase phosphatases catalyze the dephosphorylation and activation of the E1 component to reverse the effects of pyruvate dehydrogenase kinases. Pyruvate dehydrogenase phosphatase is a heterodimer consisting of catalytic and regulatory subunits. Two catalytic subunits have been reported; one is predominantly expressed in skeletal muscle and another one is is much more abundant in the liver. The catalytic subunit, encoded by this gene, is the former, and belongs to the protein phosphatase 2C (PP2C) superfamily. Along with the pyruvate dehydrogenase complex and pyruvate dehydrogenase kinases, this enzyme is located in the mitochondrial matrix. Mutation in this gene causes pyruvate dehydrogenase phosphatase deficiency. Multiple alternatively spliced transcript variants encoding different isoforms have been identified.

Source: NCBI Gene 54704 — RefSeq curated summary.

At a glance

• Gene–disease (curated): pyruvate dehydrogenase phosphatase deficiency (Strong, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 199 total — 3 pathogenic, 4 likely-pathogenic
• MANE Select transcript: NM_018444

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9279
Approved symbol	PDP1
Name	pyruvate dehydrogenase phosphatase catalytic subunit 1
Location	8q22.1
Locus type	gene with protein product
Status	Approved
Aliases	PDP, PDH, PPM2A
Ensembl gene	ENSG00000164951
Ensembl biotype	protein_coding
OMIM	605993
Entrez	54704

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 27 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000297598, ENST00000396200, ENST00000517764, ENST00000518107, ENST00000518573, ENST00000518827, ENST00000520614, ENST00000520728, ENST00000521144, ENST00000523021, ENST00000885462, ENST00000885463, ENST00000885464, ENST00000885465, ENST00000885466, ENST00000885467, ENST00000885468, ENST00000885469, ENST00000940302, ENST00000942001, ENST00000942002, ENST00000942003, ENST00000942004, ENST00000942005, ENST00000942006, ENST00000942007, ENST00000942008, ENST00000942009

RefSeq mRNA: 4 — MANE Select: NM_018444 NM_001161779, NM_001161780, NM_001161781, NM_018444

CCDS: CCDS55262, CCDS6259

Canonical transcript exons

ENST00000297598 — 2 exons

Exon	Start	End
ENSE00001668709	93922016	93926068
ENSE00002114476	93916923	93917079

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 98.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.7685 / max 442.9826, expressed in 1728 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
89765	7.5953	1578
89772	6.6672	798
89764	6.0113	1654
89763	1.4969	773
89773	0.6305	219
89768	0.2865	140
89771	0.1881	91
89766	0.1824	66
89762	0.1599	67
89770	0.1482	56

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lateral nuclear group of thalamus	UBERON:0002736	98.44	gold quality
buccal mucosa cell	CL:0002336	97.77	gold quality
biceps brachii	UBERON:0001507	97.72	gold quality
parietal lobe	UBERON:0001872	97.51	gold quality
postcentral gyrus	UBERON:0002581	97.44	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.42	gold quality
heart right ventricle	UBERON:0002080	97.40	gold quality
superior frontal gyrus	UBERON:0002661	97.30	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.24	gold quality
primary visual cortex	UBERON:0002436	97.04	gold quality
occipital lobe	UBERON:0002021	96.76	gold quality
adrenal tissue	UBERON:0018303	96.48	gold quality
middle temporal gyrus	UBERON:0002771	96.43	gold quality
adult organism	UBERON:0007023	96.11	gold quality
corpus epididymis	UBERON:0004359	95.64	gold quality
dorsal root ganglion	UBERON:0000044	94.85	gold quality
trigeminal ganglion	UBERON:0001675	94.77	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.77	gold quality
entorhinal cortex	UBERON:0002728	94.69	gold quality
vastus lateralis	UBERON:0001379	94.67	gold quality
mucosa of paranasal sinus	UBERON:0005030	94.56	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.50	gold quality
sperm	CL:0000019	94.38	gold quality
prefrontal cortex	UBERON:0000451	93.96	gold quality
oral cavity	UBERON:0000167	93.93	gold quality
lateral globus pallidus	UBERON:0002476	93.87	gold quality
right adrenal gland cortex	UBERON:0035827	93.78	gold quality
adrenal cortex	UBERON:0001235	93.76	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.73	gold quality
frontal cortex	UBERON:0001870	93.68	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8530	yes	562.41
E-ANND-3	yes	5.44

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1I2, NR1I3, TBPL1, TBX2, TBXT, TP53, ZNF699

miRNA regulators (miRDB)

90 targeting PDP1, 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-8485	100.00	77.57	4731
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-8084	99.73	69.57	1760

Literature-anchored findings (GeneRIF, showing 15)

• In cultured skin fibroblasts from three patients with congenital lactic acidemia due to a defect in activation of the pyruvate dehydrogenase complex, the PDP-activity was significantly reduced to 50.7%, 64.6% and 63.1% of that of control fibroblasts. (PMID:1327585)
• pyruvate dehydrogenase phosphatase PDP1 is down-regulated in circulating lymphocytes of obese subjects because it is poorly sensitive to magnesium/calcium; this defect is attenuated when plasma insulin is greatly enhanced (PMID:15897476)
• Lower accumulation of free ADP and AMP after the FAT-adapt trial may be responsible for the decreased glycogenolysis and PDH activation during sprinting. (PMID:16188909)
• In postmortem tissue samples, from male child with metabolic acidosis, PDK normally reduced PDH-activity in ATP-presence. Addition of Ca++ and Mg++ did not restored PDH-activity. The defect was attributed to a markedly reduced PDP-activity. (PMID:172850)
• catalytic subunit of PDP1 crystals belonged to space group P4(1)2(1)2 or P4(3)2(1)2, with unit-cell parameters a = b = 65.1, c = 216.1 A. (PMID:20208177)
• Although 7 days of bed rest induced whole body glucose intolerance, exercise-induced PDH regulation in skeletal muscle was not changed, suggesting that exercise-induced PDH regulation in skeletal muscle is maintained in glucose-intolerant individuals. (PMID:21680880)
• the pyruvate dehydrogenase complex is regulated by Tyr phosphorylation of PDP1, which toggles recruitment between ACAT1 and SIRT3 (PMID:24486017)
• YB-1 phosphorylation at Ser-102 is an important prerequisite for CCL5 promoter activation during macrophage differentiation (PMID:24962578)
• High PDH expression is associated with glucose intolerance. (PMID:28148899)
• Mitochondrial dysfunction induces radioresistance in colorectal cancer by activating [Ca(2+)]m-PDP1-PDH-histone acetylation retrograde signaling. (PMID:34489398)
• PDP1 is a key metabolic gatekeeper and modulator of drug resistance in FLT3-ITD-positive acute myeloid leukemia. (PMID:37935978)
• PDP1 promotes the progression of breast cancer through STAT3 pathway. (PMID:38566355)
• PDP1 promotes KRAS mutant colorectal cancer progression by serving as a scaffold for BRAF and MEK1. (PMID:38849010)
• Functional characterization of the bovine counterpart. (PMID:8396421)
• Functional characterization of the rat counterpart. (PMID:9651365)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	pdp1	ENSDARG00000076308
mus_musculus	Pdp1	ENSMUSG00000049225
rattus_norvegicus	Pdp1	ENSRNOG00000016180
drosophila_melanogaster	Pdp	FBGN0029958
drosophila_melanogaster	CG10376	FBGN0032702
caenorhabditis_elegans	pdp-1	WBGENE00022832

Paralogs (16): PPM1F (ENSG00000100034), TAB1 (ENSG00000100324), PPM1A (ENSG00000100614), PPM1H (ENSG00000111110), PPM1G (ENSG00000115241), ILKAP (ENSG00000132323), PPM1B (ENSG00000138032), PPM1J (ENSG00000155367), PPM1L (ENSG00000163590), PPM1K (ENSG00000163644), PPM1M (ENSG00000164088), PPM1D (ENSG00000170836), PDP2 (ENSG00000172840), PPM1E (ENSG00000175175), PP2D1 (ENSG00000183977), PPM1N (ENSG00000213889)

Protein

Protein identifiers

[Pyruvate dehydrogenase [acetyl-transferring]]-phosphatase 1, mitochondrial — Q9P0J1 (reviewed: Q9P0J1)

Alternative names: Protein phosphatase 2C, Pyruvate dehydrogenase phosphatase catalytic subunit 1

All UniProt accessions (6): E5RFL8, E5RHB9, E5RI96, E5RIE5, E5RIV4, Q9P0J1

UniProt curated annotations — full annotation on UniProt →

Function. Mitochondrial enzyme that catalyzes the dephosphorylation and concomitant reactivation of the alpha subunit of the E1 component of the pyruvate dehydrogenase complex (PDC), thereby stimulating the conversion of pyruvate into acetyl-CoA.

Subunit / interactions. Heterodimer of a catalytic (PDP1) and a regulatory (PDPR) subunit.

Subcellular location. Mitochondrion.

Disease relevance. Pyruvate dehydrogenase phosphatase deficiency (PDP deficiency) [MIM:608782] Results in lactic acidosis leading to neurological dysfunction. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Magnesium-dependent and calcium-stimulated. PDP1 activity strongly depends on its Ca(2+)-dependent binding to the lipoyl domain of E2 subunit of component of the pyruvate dehydrogenase complex.

Cofactor. Binds 2 Mn2(+) per subunit. Binds 2 Mg(2+) ions per subunit. Mn(2+) can substitute Mg2(+) for catalytic activity.

Similarity. Belongs to the PP2C family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9P0J1-1	1	yes
Q9P0J1-2	2

RefSeq proteins (4): NP_001155251, NP_001155252, NP_001155253, NP_060914* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000222	PP2C_BS	Binding_site
IPR001932	PPM-type_phosphatase-like_dom	Domain
IPR015655	PP2C	Family
IPR036457	PPM-type-like_dom_sf	Homologous_superfamily

Pfam: PF00481

Enzyme classification (BRENDA):

• EC 3.1.3.43 — [pyruvate dehydrogenase (acetyl-transferring)]-phosphatase (BRENDA: 11 organisms, 19 substrates, 32 inhibitors, 15 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

7 substrates with measured Km, best-characterized 7. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
[PYRUVATE DEHYDROGENASE (LIPOAMIDE)]-PHOSPHATE	0.0029–0.058	7
P-NITROPHENYL PHOSPHATE	29.3–55.1	3
PEPTIDE T-1	0.625	1
PEPTIDE T-2	0.22	1
PEPTIDE T-3	0.106	1
RRAS(P)VA	0.053	1
RRAT(P)VA	0.018	1

Catalyzed reactions (Rhea), 1 shown:

• O-phospho-L-seryl-[pyruvate dehydrogenase E1 alpha subunit] + H2O = L-seryl-[pyruvate dehydrogenase E1 alpha subunit] + phosphate (RHEA:12669)

UniProt features (17 total): sequence conflict 5, binding site 5, sequence variant 2, transit peptide 1, chain 1, domain 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P0J1-F1	83.41	0.68

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 (5): 144; 144; 145; 418; 516

Post-translational modifications (1): 202

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-204174	Regulation of pyruvate dehydrogenase (PDH) complex

MSigDB gene sets: 305 (showing top): ATF_B, AHRARNT_01, GOBP_POSITIVE_REGULATION_OF_AMIDE_METABOLIC_PROCESS, CREBP1_Q2, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ACETYL_COA_METABOLIC_PROCESS, GOBP_KETONE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_REGULATION_OF_FATTY_ACID_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, CREB_Q4, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_REGULATION_OF_LIPID_METABOLIC_PROCESS

GO Biological Process (4): peptidyl-threonine dephosphorylation (GO:0035970), positive regulation of pyruvate decarboxylation to acetyl-CoA (GO:0140176), protein dephosphorylation (GO:0006470), regulation of pyruvate decarboxylation to acetyl-CoA (GO:0010510)

GO Molecular Function (7): protein serine/threonine phosphatase activity (GO:0004722), [pyruvate dehydrogenase (acetyl-transferring)]-phosphatase activity (GO:0004741), metal ion binding (GO:0046872), phosphoprotein phosphatase activity (GO:0004721), protein binding (GO:0005515), hydrolase activity (GO:0016787), cation binding (GO:0043169)

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), pyruvate dehydrogenase (lipoamide) phosphatase complex (GO:0045253)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Regulation of pyruvate metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
pyruvate decarboxylation to acetyl-CoA	2
cytoplasm	2
protein dephosphorylation	1
regulation of pyruvate decarboxylation to acetyl-CoA	1
positive regulation of acetyl-CoA biosynthesis	1
dephosphorylation	1
protein modification process	1
regulation of acyl-CoA biosynthetic process	1
phosphoprotein phosphatase activity	1
protein serine/threonine phosphatase activity	1
cation binding	1
phosphatase activity	1
catalytic activity, acting on a protein	1
binding	1
catalytic activity	1
ion binding	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1
protein serine/threonine phosphatase complex	1

Protein interactions and networks

STRING

1751 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PDP1	PDHX	O00330	937
PDP1	PPTC7	Q8NI37	894
PDP1	PDHB	P11177	852
PDP1	SFRP4	Q6FHJ7	837
PDP1	DLAT	P10515	798
PDP1	PHLPP1	O60346	770
PDP1	DLD	P09622	757
PDP1	PPM1A	P35813	740
PDP1	PDHA1	P08559	732
PDP1	DECR1	Q16698	721
PDP1	CNGB3	Q9NQW8	686
PDP1	PDK4	Q16654	576
PDP1	PDK2	Q15119	570
PDP1	PDK3	Q15120	547
PDP1	PHLPP2	Q6ZVD8	547

IntAct

70 interactions, top by confidence:

A	B	Type	Score
SAMD4B	YWHAQ	psi-mi:“MI:0914”(association)	0.850
PCGF2	CBX4	psi-mi:“MI:0914”(association)	0.840
SDHA	SDHB	psi-mi:“MI:0914”(association)	0.820
PSMD10	PSMD11	psi-mi:“MI:0914”(association)	0.800
LATS2	MOB1A	psi-mi:“MI:0914”(association)	0.740
MRPL37	HSPD1	psi-mi:“MI:0914”(association)	0.710
NDUFA9	NDUFS4	psi-mi:“MI:0914”(association)	0.640
CBFA2T2	PDP1	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	PDP1	psi-mi:“MI:0915”(physical association)	0.560
KRTAP6-2	PDP1	psi-mi:“MI:0915”(physical association)	0.560
INCA1	PDP1	psi-mi:“MI:0915”(physical association)	0.560
SNUPN	TOE1	psi-mi:“MI:0914”(association)	0.530
PNOC	CETN3	psi-mi:“MI:0914”(association)	0.530
ADIPOQ	C1QL1	psi-mi:“MI:0914”(association)	0.530
SNUPN	HSPA2	psi-mi:“MI:0914”(association)	0.530
BMP4	UBE2O	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
TSSC4	SNRNP200	psi-mi:“MI:0914”(association)	0.530
PDP1	PDHA1	psi-mi:“MI:0203”(dephosphorylation reaction)	0.440
PKP3	PDP1	psi-mi:“MI:0915”(physical association)	0.400
SIRT4	VWA8	psi-mi:“MI:0914”(association)	0.350
SAMD4A	INPPL1	psi-mi:“MI:0914”(association)	0.350
TRMT1	HDAC3	psi-mi:“MI:0914”(association)	0.350
WDR44	ASMTL	psi-mi:“MI:0914”(association)	0.350
BMP4	PROS1	psi-mi:“MI:0914”(association)	0.350
SPRED2	STOM	psi-mi:“MI:0914”(association)	0.350

BioGRID (131): PDP1 (Two-hybrid), PDP1 (Affinity Capture-MS), PDP1 (Affinity Capture-MS), PDP1 (Affinity Capture-MS), PDHA1 (Biochemical Activity), PDHA1 (Reconstituted Complex), PDP1 (Biochemical Activity), PDP1 (Biochemical Activity), ACAT1 (Affinity Capture-Western), SIRT3 (Affinity Capture-Western), PDP1 (Affinity Capture-Western), PDP1 (Affinity Capture-Western), ACAT1 (Reconstituted Complex), FGFR1 (Reconstituted Complex), SIRT3 (Reconstituted Complex)

ESM2 similar proteins: A0A3L7I2I8, A3A8W2, A4IF63, A6K136, D2GXS7, D3ZQG6, F7H9X2, O60733, O62829, O62830, O75688, O88483, P20650, P35813, P35814, P35816, P42694, P49443, P93006, P97570, P97819, Q05AL2, Q15750, Q28DF4, Q2PC20, Q3UV70, Q5F361, Q5R522, Q5RA52, Q5SMK6, Q69QZ0, Q69VD9, Q6ING9, Q6NYU2, Q6ZHC8, Q7XJ53, Q7XUC5, Q84JD5, Q8AYC9, Q8BXN7

Diamond homologs: A0A7U2MSD6, A0BLX0, A0BQL0, A0CUB5, A0DSB3, A0DTY1, A3A8W2, A3A8W6, A3CCP9, A5PJZ2, A6K136, B8NLZ3, G0RT93, O04719, O62829, O62830, O75688, O81716, O88483, P20650, P34221, P35813, P35814, P35815, P35816, P36982, P36993, P39966, P49443, P49444, P49595, P49596, P49597, P49598, P93006, Q09172, Q09173, Q0DBU3, Q0IIF0, Q0JL75

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
PDP1	down-regulates	SMAD1	dephosphorylation
PDP1	“up-regulates activity”	PDHA1	dephosphorylation
FGFR1	“down-regulates activity”	PDP1	phosphorylation
ABL1	“down-regulates activity”	PDP1	phosphorylation
JAK2	“down-regulates activity”	PDP1	phosphorylation
ACAT1	“down-regulates activity”	PDP1	acetylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 91 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
RHO GTPases activate PKNs	6	27.2×	4e-05
Aerobic respiration and respiratory electron transport	6	7.6×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	4
Uncertain significance	103
Likely benign	73
Benign	1

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
2427439	NC_000008.10:g.(?94767143)(94935901_?)del	Pathogenic
4663	NM_018444.4(PDP1):c.851_853del (p.Leu284del)	Pathogenic
4664	NM_018444.4(PDP1):c.277G>T (p.Glu93Ter)	Pathogenic
3596009	NM_018444.4(PDP1):c.48dup (p.Leu17fs)	Likely pathogenic
391847	NM_018444.4(PDP1):c.1263G>A (p.Trp421Ter)	Likely pathogenic
422914	NM_018444.4(PDP1):c.467_547delinsCT (p.Ser156fs)	Likely pathogenic
982568	NM_018444.4(PDP1):c.500dup (p.Leu167fs)	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000433468 (8:93919051 G>A), RS1000487025 (8:93923877 A>G), RS1000809204 (8:93924789 G>A), RS1000839362 (8:93923612 T>C), RS1001038662 (8:93917524 G>A), RS1001222329 (8:93921889 G>A,T), RS1001284826 (8:93916816 G>A,C,T), RS1001324533 (8:93923467 T>A,C), RS1001491146 (8:93917070 G>A), RS1001704519 (8:93920591 C>G,T), RS1001751458 (8:93920318 T>C), RS1002960195 (8:93915860 G>C), RS1003006269 (8:93916840 T>C,G), RS1003012204 (8:93916189 T>G), RS1003409409 (8:93921663 C>T)

Disease associations

OMIM: gene MIM:605993 | disease phenotypes: MIM:608782, MIM:213300, MIM:249000

GenCC curated gene-disease

Disease	Classification	Inheritance
pyruvate dehydrogenase phosphatase deficiency	Strong	Autosomal recessive
Tourette syndrome	No Known Disease Relationship	Unknown

Mondo (4): pyruvate dehydrogenase phosphatase deficiency (MONDO:0012120), Joubert syndrome (MONDO:0018772), Meckel syndrome (MONDO:0018921), Tourette syndrome (MONDO:0007661)

Orphanet (3): Pyruvate dehydrogenase phosphatase deficiency (Orphanet:79246), Isolated Joubert syndrome (Orphanet:475), Meckel syndrome (Orphanet:564)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D005879	Tourette Syndrome	C10.228.140.079.898; C10.228.662.825.800; C10.574.500.850; C16.320.400.820; F03.625.992.850
C536258	Pyruvate dehydrogenase phosphatase deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects expression, affects cotreatment, decreases expression	4
Valproic Acid	affects expression, decreases methylation, increases expression	3
Cyclosporine	decreases expression, increases expression	3
Tetrachlorodibenzodioxin	increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, affects expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
dicrotophos	decreases expression	1
testosterone enanthate	affects expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
bisphenol A	decreases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
torcetrapib	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
NSC 689534	affects binding, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Calcitriol	decreases expression	1
Carbamazepine	affects expression	1
Copper	affects binding, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TC84	HAP1 PDP1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00152750	PHASE4	UNKNOWN	Study of Clonidine on Sleep Architecture in Children With Tourette’s Syndrome (TS) and Comorbid ADHD
NCT00226824	PHASE4	TERMINATED	Safety Study of Galantamine in Tic Disorders
NCT00241176	PHASE4	COMPLETED	Open Label Trial of Aripiprazole in Children and Adolescents With Tourette’s Disorder
NCT00370838	PHASE4	COMPLETED	Comparison of Keppra and Clonidine in the Treatment of Tics
NCT01018056	PHASE4	COMPLETED	Developing New Treatments for Tourette Syndrome: Therapeutic Trials With Modulators of Glutamatergic Neurotransmission
NCT01547000	PHASE4	COMPLETED	Guanfacine in Children With Tic Disorders
NCT03239210	PHASE4	COMPLETED	Effects of Ondansetron in Obsessive-compulsive and Tic Disorders
NCT00004376	PHASE3	COMPLETED	Phase III Randomized, Double-Blind, Placebo-Controlled Study of Guanfacine for Tourette Syndrome and Attention Deficit Hyperactivity Disorder
NCT00206323	PHASE3	COMPLETED	A Randomized, Placebo-controlled, Tourette Syndrome Study.
NCT00206336	PHASE3	COMPLETED	An Open-label Study to Determine the Efficacy and Safety of Topiramate in the Treatment of Tourette Syndrome.
NCT00478842	PHASE3	COMPLETED	Pallidal Stimulation and Gilles de la Tourette Syndrome
NCT00681863	PHASE3	TERMINATED	Open-label Extension Study of Pramipexole in the Treatment of Children and Adolescents With Tourette Syndrome
NCT01501695	PHASE3	COMPLETED	Phase III Study of 5LGr to Treat Tic Disorder
NCT03087201	PHASE3	COMPLETED	CANNAbinoids in the Treatment of TICS (CANNA-TICS)
NCT03487783	PHASE3	COMPLETED	Aripiprazole Oral Solution in the Treatment of Children and Adolescents With Tourette’s Syndrome
NCT03567291	PHASE3	TERMINATED	Evaluation of Safety and Tolerability of Long-term TEV-50717 (Deutetrabenazine) for Treatment of Tourette Syndrome in Children and Adolescents
NCT03571256	PHASE3	COMPLETED	A Study to Test if TEV-50717 is Effective in Relieving Tics Associated With Tourette Syndrome (TS)
NCT06021522	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate Long-term Safety of Ecopipam Tablets in Children, Adolescents and Adults With Tourette’s Disorder
NCT00004393	PHASE2	COMPLETED	Phase II Double Blind Placebo Controlled Trial of Risperidone in Tourette Syndrome
NCT00004652	PHASE2	COMPLETED	Phase II Pilot Controlled Study of Short Vs Longer Term Pimozide (Orap) Therapy in Tourette Syndrome
NCT00231985	PHASE2	COMPLETED	Effectiveness of Behavior Therapy and Psychosocial Therapy for the Treatment of Tourette Syndrome and Chronic Tic Disorder
NCT00311909	PHASE2	COMPLETED	Thalamic Deep Brain Stimulation for Tourette Syndrome
NCT00529308	PHASE2	COMPLETED	Transcranial Magnetic Stimulation (TMS) for Individuals With Tourette’s Syndrome
NCT00558467	PHASE2	COMPLETED	Pramipexole Pilot Phase II Study in Children and Adolescents With Tourette Disorder According to DSM-IV Criteria
NCT01043549	PHASE2	TERMINATED	Repetitive Transcranial Magnetic Stimulation of the Posterior Parietal Cortex in Patients Suffering From Gilles de la Tourette Syndrome
NCT01133353	PHASE2	WITHDRAWN	A Study of the Effectiveness and Safety of Tetrabenazine MR in Pediatric Subjects With Tourette’s Syndrome
NCT01475383	PHASE2	WITHDRAWN	Study Evaluating The Safety And Efficacy Of PF-03654746 In Adult Subjects With Tourette’s Syndrome
NCT01647269	PHASE2	COMPLETED	A Trial of Bilateral Deep Brain Stimulation to the Globus Pallidus Internum in Tourette Syndrome
NCT01904773	PHASE2	COMPLETED	Safety, Tolerability, Pharmacokinetic, and Efficacy Study of AZD5213 in Adolescents With Tourette’s Disorder
NCT02102698	PHASE2	COMPLETED	Ecopipam Treatment of Tourette’s Syndrome in Subjects 7-17 Years
NCT02217007	PHASE2	WITHDRAWN	A Trial Evaluating the Efficacy, Safety, and Pharmacokinetics of SNC-102 in Subjects With Tourette Syndrome
NCT02247206	PHASE2	COMPLETED	VoIP Delivered Behavior Therapy for Tourette Syndrome
NCT02581865	PHASE2	COMPLETED	Safety and Efficacy Study of NBI-98854 in Adults With Tourette Syndrome
NCT02619084	PHASE2	COMPLETED	Subthalamic Stimulation in Tourette’s Syndrome
NCT02679079	PHASE2	COMPLETED	Safety and Efficacy Study of NBI-98854 in Children and Adolescents With Tourette Syndrome
NCT02879578	PHASE2	COMPLETED	Safety and Tolerability Study of NBI-98854 for the Treatment of Subjects With Tourette Syndrome
NCT03066193	PHASE2	COMPLETED	Efficacy of a Therapeutic Combination of Dronabinol and PEA for Tourette Syndrome
NCT03247244	PHASE2	TERMINATED	Safety and Efficacy of Cannabis in Tourette Syndrome
NCT03325010	PHASE2	COMPLETED	Safety, Tolerability, and Efficacy of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome
NCT03444038	PHASE2	COMPLETED	Open-Label Safety and Tolerability Study of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome