PDHA1 (pyruvate dehydrogenase E1 subunit alpha 1)

Gene

• Entrez ID: 5160
• Gene name: Pyruvate dehydrogenase E1 subunit alpha 1
• Gene symbol: PDHA1
• Synonyms: PDHA, PDHAD, PDHCE1A, PHE1A
• Chromosome: X
• Chromosome location: Xp22.12
• Summary: The pyruvate dehydrogenase (PDH) complex is a nuclear-encoded mitochondrial multienzyme complex that catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), 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 alpha 1 subunit containing the E1 active site, and plays a key role in the function of the PDH complex. Mutations in this gene are associated with pyruvate dehydrogenase E1-alpha deficiency and X-linked Leigh syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2010]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs2229137	A>C	Pathogenic, benign	Coding sequence variant, missense variant
rs121917898	A>C	Pathogenic	Coding sequence variant, missense variant
rs137853251	AGA>-,AGAAAGA	Pathogenic	Coding sequence variant, frameshift variant, inframe deletion
rs137853252	C>T	Pathogenic	Coding sequence variant, missense variant
rs137853253	A>C	Pathogenic	Coding sequence variant, missense variant
rs137853254	C>G,T	Pathogenic	Coding sequence variant, synonymous variant, missense variant
rs137853255	T>A	Pathogenic	Coding sequence variant, missense variant
rs137853256	G>A	Pathogenic	Coding sequence variant, missense variant
rs137853257	G>C	Pathogenic	Coding sequence variant, missense variant
rs137853258	G>A	Pathogenic	Coding sequence variant, missense variant
rs137853259	C>G	Pathogenic	Coding sequence variant, missense variant
rs138727886	G>A	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant
rs141862527	G>A	Likely-benign, conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant
rs398123300	C>T	Pathogenic	Synonymous variant, coding sequence variant
rs606231185	AGTAAGA>-	Pathogenic	Frameshift variant, coding sequence variant
rs606231188	->TAGTTACCGTACACGAGAAGA	Pathogenic	Splice acceptor variant, intron variant, coding sequence variant
rs606231190	->T	Pathogenic	Frameshift variant, coding sequence variant
rs757654963	A>C	Likely-benign, conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs794727621	T>C	Conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs794729213	G>A	Pathogenic	Missense variant, coding sequence variant
rs863224145	C>A,T	Uncertain-significance, likely-pathogenic	Missense variant, coding sequence variant
rs863224148	C>T	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant
rs863224149	G>A	Pathogenic	Synonymous variant, splice acceptor variant, coding sequence variant
rs863224150	C>T	Pathogenic	Missense variant, coding sequence variant
rs863224153	TAAG>-	Pathogenic	Frameshift variant, coding sequence variant
rs863224155	GTACAGTCACTTGTTCATGGTGGTTTG>-	Pathogenic	Intron variant, splice donor variant, coding sequence variant
rs863224157	->CTTGCCAGTGTGGA	Pathogenic	Frameshift variant, coding sequence variant
rs886039690	G>T	Pathogenic	Splice acceptor variant
rs886041793	->G	Pathogenic	Frameshift variant, coding sequence variant
rs886042089	T>C	Likely-pathogenic	Missense variant, coding sequence variant
rs1057518173	->TCAGGAAGTAAG	Pathogenic	Coding sequence variant, inframe insertion
rs1057518702	A>G	Pathogenic	Splice acceptor variant, intron variant
rs1057521993	G>A	Likely-pathogenic	Missense variant, coding sequence variant
rs1057523018	T>G	Likely-pathogenic	Missense variant, coding sequence variant
rs1064793225	T>G	Likely-pathogenic	Missense variant, coding sequence variant
rs1064794149	G>A	Pathogenic	Missense variant, coding sequence variant
rs1131691792	C>T	Pathogenic	Missense variant, coding sequence variant
rs1131691952	C>T	Likely-pathogenic	Missense variant, coding sequence variant
rs1131692230	A>G	Likely-pathogenic	Missense variant, coding sequence variant
rs1157736285	A>C,G	Likely-pathogenic	Coding sequence variant, missense variant
rs1272572107	C>G,T	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant
rs1555933643	G>A	Likely-pathogenic	Missense variant, coding sequence variant
rs1555933663	G>A	Likely-pathogenic	Missense variant, coding sequence variant
rs1555933954	C>T	Likely-pathogenic	Missense variant, coding sequence variant
rs1555933963	A>G	Pathogenic	Missense variant, coding sequence variant
rs1555934165	T>G	Likely-pathogenic	Intron variant, missense variant, coding sequence variant
rs1555934376	A>C	Pathogenic	Missense variant, coding sequence variant
rs1555934379	C>T	Pathogenic, likely-pathogenic	Synonymous variant, coding sequence variant
rs1555934383	C>G	Likely-pathogenic	Missense variant, coding sequence variant
rs1555934843	G>A	Pathogenic	Splice acceptor variant
rs1555934859	->TTAC	Pathogenic	Frameshift variant, coding sequence variant
rs1555935197	A>G	Pathogenic	Splice acceptor variant
rs1555935216	TAAG>-	Pathogenic	Frameshift variant, coding sequence variant
rs1555935223	AAG>-	Pathogenic	Inframe deletion, coding sequence variant
rs1555935473	->AGAT	Pathogenic	Frameshift variant, coding sequence variant
rs1569189834	G>A	Pathogenic	Splice acceptor variant
rs1569190079	G>T	Pathogenic	Coding sequence variant, missense variant
rs1569190422	->CT	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1569190962	A>G	Pathogenic	Coding sequence variant, missense variant
rs1569191372	G>A	Pathogenic	Coding sequence variant, missense variant, intron variant
rs1569191659	G>A,T	Pathogenic, likely-pathogenic	Coding sequence variant, stop gained, missense variant
rs1569191879	AG>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1569194036	GAGGAAGGAGATTG>-	Pathogenic	Coding sequence variant, frameshift variant
rs1602227631	->AGCCAGCACTGATTACTACAAGAGAGGC	Pathogenic	Coding sequence variant, inframe indel, stop gained
rs1602227643	->TACT	Pathogenic	Coding sequence variant, frameshift variant
rs1602227679	C>T	Likely-pathogenic	Coding sequence variant, missense variant
rs1602228017	->ATCTG	Pathogenic	Coding sequence variant, frameshift variant
rs1602231539	->AGTAAGAGTGACCCTATTATGCTTCTCAAGGACAGGATGGTGAACAGCAATCTTGCCAG	Pathogenic	Coding sequence variant, inframe indel, stop gained

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT030647	hsa-miR-22-3p	Sequencing	20371350
MIRT037151	hsa-miR-877-3p	CLASH	23622248
MIRT038319	hsa-miR-130b-5p	CLASH	23622248
MIRT043636	hsa-miR-326	CLASH	23622248
MIRT045791	hsa-miR-191-5p	CLASH	23622248
MIRT443188	hsa-miR-6739-5p	PAR-CLIP	22100165
MIRT443189	hsa-miR-498	PAR-CLIP	22100165
MIRT443190	hsa-miR-6733-5p	PAR-CLIP	22100165
MIRT443191	hsa-miR-3153	PAR-CLIP	22100165
MIRT443192	hsa-miR-4668-5p	PAR-CLIP	22100165
MIRT443193	hsa-miR-3148	PAR-CLIP	22100165
MIRT443194	hsa-miR-4646-5p	PAR-CLIP	22100165
MIRT443195	hsa-miR-204-3p	PAR-CLIP	22100165
MIRT443196	hsa-miR-4761-5p	PAR-CLIP	22100165
MIRT443198	hsa-miR-320e	PAR-CLIP	22100165
MIRT732913	hsa-miR-96-3p	Immunoprecipitaion, Luciferase reporter assay, qRT-PCR, Western blot	26309161

Transcription factors

Transcription factor	Regulation	Reference
FOS	Unknown	8476854
JUN	Unknown	8476854
SP1	Unknown	8476854

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004739	Function	Pyruvate dehydrogenase (acetyl-transferring) activity	IBA	21873635
GO:0004739	Function	Pyruvate dehydrogenase (acetyl-transferring) activity	IDA	19081061
GO:0005515	Function	Protein binding	IPI	7782287, 12651851, 29128334, 29568061
GO:0005634	Component	Nucleus	HDA	21630459
GO:0005730	Component	Nucleolus	IDA
GO:0005739	Component	Mitochondrion	HDA	20833797
GO:0005739	Component	Mitochondrion	IDA
GO:0005759	Component	Mitochondrial matrix	TAS
GO:0005967	Component	Mitochondrial pyruvate dehydrogenase complex	IBA	21873635
GO:0006006	Process	Glucose metabolic process	IEA
GO:0006086	Process	Acetyl-CoA biosynthetic process from pyruvate	IBA	21873635
GO:0006086	Process	Acetyl-CoA biosynthetic process from pyruvate	IDA	19081061
GO:0006090	Process	Pyruvate metabolic process	TAS
GO:0006099	Process	Tricarboxylic acid cycle	IEA
GO:0034604	Function	Pyruvate dehydrogenase (NAD+) activity	IEA
GO:0045254	Component	Pyruvate dehydrogenase complex	IDA	19081061
GO:0061732	Process	Mitochondrial acetyl-CoA biosynthetic process from pyruvate	IEA

Other IDs

• MIM: 300502
• HGNC: 8806
• e!Ensembl: ENSG00000131828

Protein

• UniProt ID: P08559
• Protein name: Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial (EC 1.2.4.1) (PDHE1-A type I)
• Protein function: The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.
• PDB: 1NI4, 2OZL, 3EXE, 3EXF, 3EXG, 3EXH, 3EXI, 6CER, 6CFO
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00676	E1_dh	66 → 362	Dehydrogenase E1 component	Family

• Sequence:

  MRKMLAAVSRVLSGASQKPASRVLVASRNFANDATFEIKKCDLHRLEEGPPVTTVLTRED
  GLKYYRMMQTVRRMELKADQLYKQKIIRGFCHLCDGQEACCVGLEAGINPTDHLITAYRA
  HGFTFTRGLSVREILAELTGRKGGCAKGKGGSMHMYAKNFYGGNGIVGAQVPLGAGIALA
  CKYNGKDEVCLTLYGDGAANQGQIFEAYNMAALWKLPCIFICENNRYGMGTSVERAAAST
  DYYKRGDFIPGLRVDGMDILCVREATRFAAAYCRSGKGPILMELQTYRYHGHSMSDPGVS
  YRTREEIQEVRSKSDPIMLLKDRMVNSNLASVEELKEIDVEVRKEIEDAAQFATADPEPP
  LEELGYHIYSSDPPFEVRGANQWIKFKSVS

• Sequence length: 390