ALDH5A1 (aldehyde dehydrogenase 5 family member A1)

Gene

• Entrez ID: 7915
• Gene name: Aldehyde dehydrogenase 5 family member A1
• Gene symbol: ALDH5A1
• Synonyms: SSADH, SSDH
• Chromosome: 6
• Chromosome location: 6p22.3
• Summary: This protein belongs to the aldehyde dehydrogenase family of proteins. This gene encodes a mitochondrial NAD(+)-dependent succinic semialdehyde dehydrogenase. A deficiency of this enzyme, known as 4-hydroxybutyricaciduria, is a rare inborn error in the metabolism of the neurotransmitter 4-aminobutyric acid (GABA). In response to the defect, physiologic fluids from patients accumulate GHB, a compound with numerous neuromodulatory properties. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs72552281	G>A	Pathogenic	Coding sequence variant, missense variant
rs72552282	G>A	Likely-pathogenic	Coding sequence variant, missense variant
rs72552284	G>A,C	Likely-pathogenic	Coding sequence variant, missense variant
rs115784602	G>A	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Missense variant, coding sequence variant
rs118203982	G>A	Pathogenic	Stop gained, coding sequence variant
rs118203983	C>T	Pathogenic	Stop gained, coding sequence variant
rs118203984	G>A	Pathogenic	Missense variant, coding sequence variant
rs142482046	A>C	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Missense variant, coding sequence variant
rs144177566	G>A,C,T	Uncertain-significance, benign-likely-benign, conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant
rs145208127	C>A,T	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant
rs147358733	G>A	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant
rs148188703	C>A,T	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant
rs375628463	G>A	Pathogenic-likely-pathogenic, pathogenic	Missense variant, coding sequence variant, intron variant
rs755029414	->TTGCCCT	Pathogenic	Coding sequence variant, frameshift variant
rs778127154	T>-	Pathogenic	Intron variant, frameshift variant, coding sequence variant
rs875989801	GTA>TT	Pathogenic	Intron variant, splice donor variant
rs1301821497	A>G	Pathogenic	Splice acceptor variant
rs1306678453	C>-	Pathogenic	Coding sequence variant, frameshift variant
rs1561872640	G>A	Pathogenic	Splice donor variant, intron variant
rs1561879345	->G	Pathogenic-likely-pathogenic	Coding sequence variant, frameshift variant
rs1561879380	G>A,T	Pathogenic	Splice donor variant
rs1581807379	G>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1581815207	T>-	Likely-pathogenic	Coding sequence variant, frameshift variant, intron variant
rs1581819950	C>T	Likely-pathogenic	Stop gained, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT020822	hsa-miR-155-5p	Proteomics	18668040
MIRT024624	hsa-miR-215-5p	Microarray	19074876
MIRT026627	hsa-miR-192-5p	Microarray	19074876
MIRT030518	hsa-miR-24-3p	Microarray	19748357
MIRT047973	hsa-miR-30c-5p	CLASH	23622248
MIRT054203	hsa-miR-210-3p	Luciferase reporter assay, Microarray, qRT-PCR, Western blot	23028679
MIRT054214	hsa-miR-147b	Luciferase reporter assay, Microarray, qRT-PCR, Western blot	23028679
MIRT646558	hsa-miR-4279	HITS-CLIP	23824327
MIRT646559	hsa-miR-6783-3p	HITS-CLIP	23824327
MIRT646560	hsa-miR-1343-3p	HITS-CLIP	23824327
MIRT646561	hsa-miR-525-5p	HITS-CLIP	23824327
MIRT646562	hsa-miR-520a-5p	HITS-CLIP	23824327
MIRT646563	hsa-miR-23b-5p	HITS-CLIP	23824327
MIRT646564	hsa-miR-23a-5p	HITS-CLIP	23824327
MIRT646565	hsa-miR-1976	HITS-CLIP	23824327
MIRT646566	hsa-miR-3653-5p	HITS-CLIP	23824327
MIRT646567	hsa-miR-6742-3p	HITS-CLIP	23824327
MIRT646568	hsa-miR-6852-5p	HITS-CLIP	23824327
MIRT646569	hsa-miR-939-3p	HITS-CLIP	23824327
MIRT646570	hsa-miR-6727-3p	HITS-CLIP	23824327
MIRT646571	hsa-miR-4722-3p	HITS-CLIP	23824327
MIRT646572	hsa-miR-122-3p	HITS-CLIP	23824327
MIRT680046	hsa-miR-365b-5p	HITS-CLIP	23824327
MIRT680047	hsa-miR-365a-5p	HITS-CLIP	23824327
MIRT680048	hsa-miR-8052	HITS-CLIP	23824327
MIRT680049	hsa-miR-3199	HITS-CLIP	23824327
MIRT680050	hsa-miR-6747-3p	HITS-CLIP	23824327
MIRT717841	hsa-miR-561-5p	HITS-CLIP	19536157
MIRT717842	hsa-miR-524-5p	HITS-CLIP	19536157
MIRT717843	hsa-miR-520d-5p	HITS-CLIP	19536157
MIRT717844	hsa-miR-4437	HITS-CLIP	19536157
MIRT717845	hsa-miR-6847-3p	HITS-CLIP	19536157
MIRT717846	hsa-miR-6781-3p	HITS-CLIP	19536157
MIRT717847	hsa-miR-2682-3p	HITS-CLIP	19536157
MIRT717848	hsa-miR-1283	HITS-CLIP	19536157
MIRT717849	hsa-miR-877-3p	HITS-CLIP	19536157
MIRT717850	hsa-miR-5088-5p	HITS-CLIP	19536157
MIRT717851	hsa-miR-5581-5p	HITS-CLIP	19536157
MIRT717852	hsa-miR-4297	HITS-CLIP	19536157
MIRT717853	hsa-miR-4252	HITS-CLIP	19536157
MIRT717854	hsa-miR-4520-5p	HITS-CLIP	19536157
MIRT717855	hsa-miR-1273g-3p	HITS-CLIP	19536157
MIRT732682	hsa-miR-29a-3p	EMSA, Luciferase reporter assay, qRT-PCR, Western blot	26428001

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004777	Function	Succinate-semialdehyde dehydrogenase (NAD+) activity	IBA	21873635
GO:0004777	Function	Succinate-semialdehyde dehydrogenase (NAD+) activity	IDA	9683595, 16199352
GO:0004777	Function	Succinate-semialdehyde dehydrogenase (NAD+) activity	ISS	7814412
GO:0004777	Function	Succinate-semialdehyde dehydrogenase (NAD+) activity	TAS
GO:0005739	Component	Mitochondrion	HDA	20833797
GO:0005739	Component	Mitochondrion	IDA
GO:0005739	Component	Mitochondrion	ISS
GO:0005759	Component	Mitochondrial matrix	TAS
GO:0006105	Process	Succinate metabolic process	ISS
GO:0006536	Process	Glutamate metabolic process	ISS
GO:0007417	Process	Central nervous system development	IMP	9683595
GO:0009450	Process	Gamma-aminobutyric acid catabolic process	IDA	9683595
GO:0009450	Process	Gamma-aminobutyric acid catabolic process	IEA
GO:0009450	Process	Gamma-aminobutyric acid catabolic process	IMP	15037717
GO:0009791	Process	Post-embryonic development	IEA
GO:0042135	Process	Neurotransmitter catabolic process	ISS
GO:0042802	Function	Identical protein binding	IPI	16199352

Other IDs

• MIM: 610045
• HGNC: 408
• e!Ensembl: ENSG00000112294

Protein

• UniProt ID: P51649
• Protein name: Succinate-semialdehyde dehydrogenase, mitochondrial (EC 1.2.1.24) (Aldehyde dehydrogenase family 5 member A1) (NAD(+)-dependent succinic semialdehyde dehydrogenase)
• Protein function: Catalyzes one step in the degradation of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA).
• PDB: 2W8N, 2W8O, 2W8P, 2W8Q, 2W8R
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00171	Aldedh	69 → 530	Aldehyde dehydrogenase family	Family

• Sequence:

  MATCIWLRSCGARRLGSTFPGCRLRPRAGGLVPASGPAPGPAQLRCYAGRLAGLSAALLR
  TDSFVGGRWLPAAATFPVQDPASGAALGMVADCGVREARAAVRAAYEAFCRWREVSAKER
  SSLLRKWYNLMIQNKDDLARIITAESGKPLKEAHGEILYSAFFLEWFSEEARRVYGDIIH
  TPAKDRRALVLKQPIGVAAVITPWNFPSAMITRKVGAALAAGCTVVVKPAEDTPFSALAL
  AELASQAGIPSGVYNVIPCSRKNAKEVGEAICTDPLVSKISFTGSTTTGKILLHHAANSV
  KRVSMELGGLAPFIVFDSANVDQAVAGAMASKFRNTGQTCVCSNQFLVQRGIHDAFVKAF
  AEAMKKNLRVGNGFEEGTTQGPLINEKAVEKVEKQVNDAVSKGATVVTGGKRHQLGKNFF
  EPTLLCNVTQDMLCTHEETFGPLAPVIKFDTEEEAIAIANAADVGLAGYFYSQDPAQIWR
  VAEQLEVGMVGVNEGLISSVECPFGGVKQSGLGREGSKYGIDEYLELKYVCYGGL

• Sequence length: 535