PDP1

pyruvate dehydrogenase phosphatase catalytic subunit 1, the group of Protein phosphatases, Mg2+/Mn2+ dependent

Basic information

Region (hg38): 8:93857807-93926068

Previous symbols: [ "PPM2C" ]

Links

ENSG00000164951 ∙ NCBI:54704 ∙ OMIM:605993 ∙ HGNC:9279 ∙ Uniprot:Q9P0J1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Tourette syndrome (No Known Disease Relationship), mode of inheritance: Unknown
• pyruvate dehydrogenase phosphatase deficiency (Strong), mode of inheritance: AR
• pyruvate dehydrogenase phosphatase deficiency (Moderate), mode of inheritance: AR
• pyruvate dehydrogenase phosphatase deficiency (Supportive), mode of inheritance: AR
• pyruvate dehydrogenase phosphatase deficiency (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pyruvate dehydrogenase phosphatase deficiency	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Neurologic	15855260; 19184109; 31392110
As with other conditions that involve seizures, optimal seizure control is important, and may be influenced by knowing the molecular cause

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PDP1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PDP1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	54	2	57
missense			63	1		64
nonsense		1	3			4
start loss						0
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			6	7	3	16
Total	0	2	73	62	5

Variants in PDP1

This is a list of pathogenic ClinVar variants found in the PDP1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-93916851-T-A		Pyruvate dehydrogenase phosphatase deficiency	Benign (Jun 29, 2018)
8-93917044-C-T			Likely benign (Mar 19, 2018)
8-93917186-G-T			Benign (Mar 03, 2015)
8-93917234-C-T		not specified	Likely benign (Aug 02, 2017)
8-93917366-G-C			Likely benign (Dec 01, 2021)
8-93917437-G-A			Likely benign (Jun 16, 2018)
8-93917718-C-G			Likely benign (Aug 03, 2018)
8-93917734-C-T			Benign (Jul 09, 2018)
8-93917811-T-TGCCGCCGCCTCCTC		not specified	Uncertain significance (Jun 19, 2013)
8-93921902-A-G			Likely benign (Jun 14, 2018)
8-93922057-G-A			Uncertain significance (Apr 20, 2022)
8-93922071-A-G			Likely benign (Jul 11, 2022)
8-93922080-G-C			Likely benign (May 04, 2023)
8-93922089-T-C			Likely benign (May 04, 2022)
8-93922115-G-C			Uncertain significance (Mar 13, 2022)
8-93922116-G-A			Likely benign (Dec 02, 2021)
8-93922146-C-T		not specified	Likely benign (Feb 01, 2023)
8-93922169-C-T			Uncertain significance (Jul 17, 2022)
8-93922170-G-A			Likely benign (Jun 10, 2022)
8-93922170-G-T			Likely benign (Aug 20, 2022)
8-93922182-G-T			Uncertain significance (May 25, 2022)
8-93922187-G-A		not specified	Conflicting classifications of pathogenicity (Aug 31, 2022)
8-93922213-T-C			Likely benign (Oct 03, 2023)
8-93922214-A-G		Inborn genetic diseases	Uncertain significance (Dec 01, 2022)
8-93922230-G-A			Likely benign (Aug 28, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PDP1	protein_coding	protein_coding	ENST00000396200	2	68260

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.451	0.549	125734	0	14	125748	0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.62	220	299	0.736	0.0000159	3710
Missense in Polyphen		63	122.48	0.51437		1508
Synonymous	-0.767	126	116	1.09	0.00000636	1115
Loss of Function	3.15	4	18.7	0.214	0.00000111	213

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000152	0.000152
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000939	0.0000924
European (Non-Finnish)	0.0000809	0.0000791
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the dephosphorylation and concomitant reactivation of the alpha subunit of the E1 component of the pyruvate dehydrogenase complex. {ECO:0000250}.
• Disease: DISEASE: Pyruvate dehydrogenase phosphatase deficiency (PDP deficiency) [MIM:608782]: Results in lactic acidosis leading to neurological dysfunction. {ECO:0000269|PubMed:15855260}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Regulation of pyruvate dehydrogenase (PDH) complex;Pyruvate metabolism;Pyruvate metabolism and Citric Acid (TCA) cycle;The citric acid (TCA) cycle and respiratory electron transport;Metabolism (Consensus)

Recessive Scores

• pRec: 0.475

Intolerance Scores

• loftool: 0.631
• rvis_EVS: -0.76
• rvis_percentile_EVS: 13.33

Haploinsufficiency Scores

• pHI: 0.120
• hipred: Y
• hipred_score: 0.654
• ghis: 0.590

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.499

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Pdp1

Gene ontology

• Biological process: regulation of acetyl-CoA biosynthetic process from pyruvate;peptidyl-threonine dephosphorylation;positive regulation of pyruvate dehydrogenase activity
• Cellular component: mitochondrion;mitochondrial matrix
• Molecular function: protein serine/threonine phosphatase activity;magnesium-dependent protein serine/threonine phosphatase activity;[pyruvate dehydrogenase (lipoamide)] phosphatase activity;protein binding;metal ion binding