ALDH4A1 (aldehyde dehydrogenase 4 family member A1)

Gene

• Entrez ID: 8659
• Gene name: Aldehyde dehydrogenase 4 family member A1
• Gene symbol: ALDH4A1
• Synonyms: ALDH4, P5CD, P5CDh
• Chromosome: 1
• Chromosome location: 1p36.13
• Summary: This protein belongs to the aldehyde dehydrogenase family of proteins. This enzyme is a mitochondrial matrix NAD-dependent dehydrogenase which catalyzes the second step of the proline degradation pathway, converting pyrroline-5-carboxylate to glutamate. Deficiency of this enzyme is associated with type II hyperprolinemia, an autosomal recessive disorder characterized by accumulation of delta-1-pyrroline-5-carboxylate (P5C) and proline. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jun 2009]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs78532707	C>A,G,T	Conflicting-interpretations-of-pathogenicity	Splice donor variant, intron variant
rs137852937	G>A,C	Pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs149414160	A>G	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Intron variant, missense variant, coding sequence variant, non coding transcript variant
rs387906314	C>-	Likely-pathogenic	Genic upstream transcript variant, frameshift variant, coding sequence variant, non coding transcript variant
rs779536510	->A	Pathogenic	Coding sequence variant, frameshift variant, non coding transcript variant
rs1557620472	C>G	Likely-pathogenic	Splice acceptor variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT022075	hsa-miR-128-3p	Microarray	17612493
MIRT740952	hsa-miR-3190-3p	PAR-CLIP	26701625
MIRT741496	hsa-miR-3529-5p	PAR-CLIP	26701625
MIRT742778	hsa-miR-379-5p	PAR-CLIP	26701625
MIRT742877	hsa-miR-3915	PAR-CLIP	26701625
MIRT743020	hsa-miR-3927-3p	PAR-CLIP	26701625
MIRT743032	hsa-miR-3928-3p	PAR-CLIP	26701625
MIRT745024	hsa-miR-4476	PAR-CLIP	26701625
MIRT745872	hsa-miR-4524b-3p	PAR-CLIP	26701625
MIRT747048	hsa-miR-4690-3p	PAR-CLIP	26701625
MIRT751176	hsa-miR-5685	PAR-CLIP	26701625
MIRT757127	hsa-miR-6831-5p	PAR-CLIP	26701625
MIRT757695	hsa-miR-6856-3p	PAR-CLIP	26701625
MIRT758134	hsa-miR-6876-5p	PAR-CLIP	26701625

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0003842	Function	1-pyrroline-5-carboxylate dehydrogenase activity	IBA	21873635
GO:0004029	Function	Aldehyde dehydrogenase (NAD+) activity	IDA	4015840
GO:0005515	Function	Protein binding	IPI	32814053
GO:0005739	Component	Mitochondrion	IDA
GO:0005759	Component	Mitochondrial matrix	TAS
GO:0005829	Component	Cytosol	IDA
GO:0006560	Process	Proline metabolic process	TAS	8621661
GO:0006562	Process	Proline catabolic process	TAS
GO:0009055	Function	Electron transfer activity	TAS	8621661
GO:0010133	Process	Proline catabolic process to glutamate	IEA
GO:0019470	Process	4-hydroxyproline catabolic process	TAS	21998747
GO:0022900	Process	Electron transport chain	IEA
GO:0042802	Function	Identical protein binding	IPI	22516612
GO:0046487	Process	Glyoxylate metabolic process	TAS

Other IDs

• MIM: 606811
• HGNC: 406
• e!Ensembl: ENSG00000159423

Protein

• UniProt ID: P30038
• Protein name: Delta-1-pyrroline-5-carboxylate dehydrogenase, mitochondrial (P5C dehydrogenase) (EC 1.2.1.88) (Aldehyde dehydrogenase family 4 member A1) (L-glutamate gamma-semialdehyde dehydrogenase)
• Protein function: Irreversible conversion of delta-1-pyrroline-5-carboxylate (P5C), derived either from proline or ornithine, to glutamate. This is a necessary step in the pathway interconnecting the urea and tricarboxylic acid cycles. The preferred substrate is glutamic gamma-semialdehyde, other substrates include succinic, glutaric and adipic semialdehydes.
• PDB: 3V9G, 3V9H, 3V9I, 4OE5
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00171	Aldedh	74 → 547	Aldehyde dehydrogenase family	Family

• Sequence:

  MLLPAPALRRALLSRPWTGAGLRWKHTSSLKVANEPVLAFTQGSPERDALQKALKDLKGR
  MEAIPCVVGDEEVWTSDVQYQVSPFNHGHKVAKFCYADKSLLNKAIEAALAARKEWDLKP
  IADRAQIFLKAADMLSGPRRAEILAKTMVGQGKTVIQAEIDAAAELIDFFRFNAKYAVEL
  EGQQPISVPPSTNSTVYRGLEGFVAAISPFNFTAIGGNLAGAPALMGNVVLWKPSDTAML
  ASYAVYRILREAGLPPNIIQFVPADGPLFGDTVTSSEHLCGINFTGSVPTFKHLWKQVAQ
  NLDRFHTFPRLAGECGGKNFHFVHRSADVESVVSGTLRSAFEYGGQKCSACSRLYVPHSL
  WPQIKGRLLEEHSRIKVGDPAEDFGTFFSAVIDAKSFARIKKWLEHARSSPSLTILAGGK
  CDDSVGYFVEPCIVESKDPQEPIMKEEIFGPVLSVYVYPDDKYKETLQLVDSTTSYGLTG
  AVFSQDKDVVQEATKVLRNAAGNFYINDKSTGSIVGQQPFGGARASGTNDKPGGPHYILR
  WTSPQVIKETHKPLGDWSYAYMQ

• Sequence length: 563