PDHX

pyruvate dehydrogenase complex component X, the group of Pyruvate dehydrogenase complex|MicroRNA protein coding host genes

Basic information

Region (hg38): 11:34915829-35020591

Links

ENSG00000110435

∙ NCBI:8050 ∙ OMIM:608769 ∙ HGNC:21350 ∙ Uniprot:O00330 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

pyruvate dehydrogenase E3-binding protein deficiency (Definitive), mode of inheritance: AR
pyruvate dehydrogenase E3-binding protein deficiency (Strong), mode of inheritance: AR
pyruvate dehydrogenase E3-binding protein deficiency (Strong), mode of inheritance: AR
pyruvate dehydrogenase E3-binding protein deficiency (Strong), mode of inheritance: AR
pyruvate dehydrogenase E3-binding protein deficiency (Supportive), mode of inheritance: AR
Leigh syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pyruvate dehydrogenase E3-binding protein deficiency	AR	Biochemical	Medical and dietary treatment (eg, ketogenic diet) may be beneficial	Biochemical; Neurologic	2112155; 8229524; 8584393; 9399911; 9501264; 10590436; 11935326; 12208141; 12557299; 15303005; 16566017; 16843025; 17152059; 20002125; 21914562; 21937992; 22766002; 25087164

ClinVar

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

not_provided (230 variants)
Pyruvate_dehydrogenase_E3-binding_protein_deficiency (82 variants)
Inborn_genetic_diseases (80 variants)
not_specified (40 variants)
PDHX-related_disorder (11 variants)
Mitochondrial_disease (2 variants)
Pyruvate_dehydrogenase_E1-alpha_deficiency (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PDHX gene is commonly pathogenic or not. These statistics are base on transcript: NM_000003477.3. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous		1 clinvar	2 clinvar	41 clinvar	7 clinvar	51
missense		2 clinvar	154 clinvar	15 clinvar	2 clinvar	173
nonsense	5 clinvar	6 clinvar	1 clinvar			12
start loss						0
frameshift	6 clinvar	10 clinvar	1 clinvar			17
splice donor/acceptor (+/-2bp)	5 clinvar	3 clinvar				8
Total	16	22	158	56	9

Highest pathogenic variant AF is 0.000050409577

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PDHX	protein_coding	protein_coding	ENST00000227868	11	104763

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000972	0.997	125699	1	48	125748	0.000195

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.203	289	279	1.03	0.0000147	3194
Missense in Polyphen		101	97.361	1.0374		1217
Synonymous	-0.152	101	99.1	1.02	0.00000513	1047
Loss of Function	2.64	11	25.4	0.434	0.00000130	292

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000210	0.000210
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000109	0.000109
Finnish	0.000231	0.000231
European (Non-Finnish)	0.000194	0.000193
Middle Eastern	0.000109	0.000109
South Asian	0.000491	0.000457
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Required for anchoring dihydrolipoamide dehydrogenase (E3) to the dihydrolipoamide transacetylase (E2) core of the pyruvate dehydrogenase complexes of eukaryotes. This specific binding is essential for a functional PDH complex.;
Disease: DISEASE: Pyruvate dehydrogenase E3-binding protein deficiency (PDHXD) [MIM:245349]: A metabolic disorder characterized by decreased activity of the pyruvate dehydrogenase complex without observable reduction in the activities of enzymes E1, E2, or E3. Clinical features include hypotonia and psychomotor retardation. {ECO:0000269|PubMed:9399911}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Amino Acid metabolism;Glycolysis and Gluconeogenesis;Signal Transduction;Regulation of pyruvate dehydrogenase (PDH) complex;Pyruvate metabolism;Pyruvate metabolism and Citric Acid (TCA) cycle;Metabolism of amino acids and derivatives;The citric acid (TCA) cycle and respiratory electron transport;Glycolysis and Gluconeogenesis;Metabolism;Glyoxylate metabolism and glycine degradation;Signaling by Retinoic Acid;Signaling by Nuclear Receptors (Consensus)

Recessive Scores

pRec: 0.419

Intolerance Scores

loftool: 0.901
rvis_EVS: 0.25
rvis_percentile_EVS: 69.57

Haploinsufficiency Scores

pHI: 0.0480
hipred: Y
hipred_score: 0.704
ghis: 0.547

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.949

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Pdhx
Phenotype

Gene ontology

Biological process: mitochondrial acetyl-CoA biosynthetic process from pyruvate
Cellular component: mitochondrial matrix;pyruvate dehydrogenase complex
Molecular function: protein binding;transferase activity, transferring acyl groups;pyruvate dehydrogenase (NAD+) activity