ADSL (adenylosuccinate lyase)

Gene

• Entrez ID: 158
• Gene name: Adenylosuccinate lyase
• Gene symbol: ADSL
• Synonyms: AMPS, ASASE, ASL
• Chromosome: 22
• Chromosome location: 22q13.1
• Summary: The protein encoded by this gene belongs to the lyase 1 family. It is an essential enzyme involved in purine metabolism, and catalyzes two non-sequential reactions in the de novo purine biosynthetic pathway: the conversion of succinylaminoimidazole carboxamide ribotide (SAICAR) to aminoimidazole carboxamide ribotide (AICAR) and the conversion of adenylosuccinate (S-AMP) to adenosine monophosphate (AMP). Mutations in this gene are associated with adenylosuccinase deficiency (ADSLD), a disorder marked with psychomotor retardation, epilepsy or autistic features. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2015]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs28941471	G>A	Uncertain-significance, likely-pathogenic	Upstream transcript variant, coding sequence variant, non coding transcript variant, genic upstream transcript variant, missense variant
rs34396910	A>G	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, non coding transcript variant, missense variant
rs119450940	T>C	Pathogenic	Intron variant, non coding transcript variant, genic downstream transcript variant, missense variant, coding sequence variant
rs119450941	G>A	Pathogenic, likely-pathogenic	Intron variant, non coding transcript variant, genic downstream transcript variant, missense variant, coding sequence variant
rs119450942	C>G	Pathogenic	5 prime UTR variant, non coding transcript variant, genic upstream transcript variant, missense variant, coding sequence variant
rs119450944	A>G	Likely-pathogenic	Coding sequence variant, 5 prime UTR variant, non coding transcript variant, missense variant
rs119450945	T>C	Pathogenic	Coding sequence variant, 5 prime UTR variant, non coding transcript variant, missense variant
rs143083947	C>A,G,T	Pathogenic	5 prime UTR variant, non coding transcript variant, genic upstream transcript variant, missense variant, coding sequence variant
rs143275316	T>C	Likely-benign, conflicting-interpretations-of-pathogenicity	5 prime UTR variant, synonymous variant, non coding transcript variant, genic upstream transcript variant, coding sequence variant
rs143977255	A>T	Conflicting-interpretations-of-pathogenicity, benign	Coding sequence variant, 5 prime UTR variant, non coding transcript variant, synonymous variant
rs148411623	G>A,T	Likely-benign, conflicting-interpretations-of-pathogenicity	Coding sequence variant, 5 prime UTR variant, non coding transcript variant, missense variant
rs181628906	C>T	Uncertain-significance, conflicting-interpretations-of-pathogenicity, benign	Intron variant, genic upstream transcript variant
rs199993991	G>A,T	Uncertain-significance, conflicting-interpretations-of-pathogenicity, benign	Intron variant, genic upstream transcript variant
rs200814886	G>A	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Intron variant, non coding transcript variant, genic downstream transcript variant, missense variant, coding sequence variant
rs201509960	T>C	Conflicting-interpretations-of-pathogenicity, benign	Intron variant
rs202064195	C>T	Conflicting-interpretations-of-pathogenicity, likely-pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs372895468	C>G,T	Pathogenic	Non coding transcript variant, genic downstream transcript variant, missense variant, intron variant, coding sequence variant
rs373458753	C>T	Pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs374259530	T>C	Pathogenic	Non coding transcript variant, genic upstream transcript variant, 5 prime UTR variant, missense variant, coding sequence variant
rs750614500	C>T	Pathogenic	Non coding transcript variant, upstream transcript variant, genic upstream transcript variant, coding sequence variant, stop gained
rs751928831	G>C	Conflicting-interpretations-of-pathogenicity	Synonymous variant, non coding transcript variant, upstream transcript variant, genic upstream transcript variant, coding sequence variant
rs756210458	C>G,T	Pathogenic	Non coding transcript variant, intron variant, genic upstream transcript variant, coding sequence variant, missense variant
rs761493155	C>T	Pathogenic	Coding sequence variant, non coding transcript variant, stop gained
rs761551284	G>T	Likely-pathogenic	Intron variant, genic upstream transcript variant, splice donor variant
rs763542069	G>A	Pathogenic, likely-pathogenic	Missense variant, coding sequence variant, non coding transcript variant, genic downstream transcript variant
rs771121666	T>C	Uncertain-significance, pathogenic-likely-pathogenic	Non coding transcript variant, intron variant, genic downstream transcript variant, missense variant, coding sequence variant
rs776496275	G>C	Likely-pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs777821034	T>C	Pathogenic	Non coding transcript variant, intron variant, genic downstream transcript variant, missense variant, coding sequence variant
rs796052244	G>T	Likely-pathogenic	Missense variant, non coding transcript variant, coding sequence variant, 5 prime UTR variant
rs796052246	C>G,T	Pathogenic	Missense variant, non coding transcript variant, coding sequence variant, stop gained
rs796052247	G>C	Pathogenic	Missense variant, non coding transcript variant, coding sequence variant, genic downstream transcript variant
rs796052248	C>T	Pathogenic	Non coding transcript variant, intron variant, genic downstream transcript variant, missense variant, coding sequence variant
rs879257322	C>A,T	Likely-pathogenic	Synonymous variant, non coding transcript variant, coding sequence variant, stop gained
rs1036185928	C>T	Likely-pathogenic, pathogenic	5 prime UTR variant, coding sequence variant, stop gained, non coding transcript variant, genic upstream transcript variant
rs1057521071	C>G	Likely-pathogenic, uncertain-significance	Genic downstream transcript variant, coding sequence variant, non coding transcript variant, missense variant
rs1057521795	T>C	Likely-pathogenic	Genic downstream transcript variant, coding sequence variant, non coding transcript variant, missense variant
rs1555903969	G>T	Pathogenic, uncertain-significance	Genic upstream transcript variant, intron variant, splice donor variant
rs1555908924	C>T	Likely-pathogenic	Non coding transcript variant, genic downstream transcript variant, coding sequence variant, stop gained
rs1569096551	C>T	Pathogenic	Genic upstream transcript variant, non coding transcript variant, coding sequence variant, stop gained, upstream transcript variant
rs1601552154	G>A	Pathogenic	5 prime UTR variant, genic upstream transcript variant, non coding transcript variant, coding sequence variant, missense variant
rs1601586359	C>T	Pathogenic	Non coding transcript variant, 5 prime UTR variant, missense variant, coding sequence variant
rs1601596522	CAT>-	Likely-pathogenic	Non coding transcript variant, genic downstream transcript variant, coding sequence variant, inframe deletion

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT038883	hsa-miR-93-3p	CLASH	23622248
MIRT052539	hsa-let-7a-5p	CLASH	23622248
MIRT764201	hsa-miR-25-5p	PAR-CLIP	27292025
MIRT767351	hsa-miR-377-5p	PAR-CLIP	27292025
MIRT768611	hsa-miR-4324	PAR-CLIP	27292025
MIRT770257	hsa-miR-455-3p	PAR-CLIP	27292025
MIRT775482	hsa-miR-6086	PAR-CLIP	27292025
MIRT775641	hsa-miR-6087	PAR-CLIP	27292025
MIRT776186	hsa-miR-6499-3p	PAR-CLIP	27292025
MIRT777052	hsa-miR-6516-5p	PAR-CLIP	27292025
MIRT777322	hsa-miR-658	PAR-CLIP	27292025
MIRT778464	hsa-miR-6761-5p	PAR-CLIP	27292025
MIRT779545	hsa-miR-6807-5p	PAR-CLIP	27292025

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004018	Function	N6-(1,2-dicarboxyethyl)AMP AMP-lyase (fumarate-forming) activity	IBA	21873635
GO:0004018	Function	N6-(1,2-dicarboxyethyl)AMP AMP-lyase (fumarate-forming) activity	IDA	16973378
GO:0005829	Component	Cytosol	IBA	21873635
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	TAS
GO:0006164	Process	Purine nucleotide biosynthetic process	IC	10888601
GO:0006167	Process	AMP biosynthetic process	IDA	11428554
GO:0006189	Process	'de novo' IMP biosynthetic process	IEA
GO:0009168	Process	Purine ribonucleoside monophosphate biosynthetic process	TAS
GO:0032991	Component	Protein-containing complex	IDA	16973378
GO:0042802	Function	Identical protein binding	IDA	16973378
GO:0044208	Process	'de novo' AMP biosynthetic process	IBA	21873635
GO:0044208	Process	'de novo' AMP biosynthetic process	IEA
GO:0070626	Function	(S)-2-(5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido)succinate AMP-lyase (fumarate-forming) activity	IBA	21873635

Other IDs

• MIM: 608222
• HGNC: 291
• e!Ensembl: ENSG00000239900

Protein

• UniProt ID: P30566
• Protein name: Adenylosuccinate lyase (ADSL) (ASL) (EC 4.3.2.2) (Adenylosuccinase) (ASase)
• Protein function: Catalyzes two non-sequential steps in de novo AMP synthesis: converts (S)-2-(5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido)succinate (SAICAR) to fumarate plus 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide, and thereby also contributes to de novo IMP synthesis, and converts succinyladenosine monophosphate (SAMP) to AMP and fumarate.
• PDB: 2J91, 2VD6, 4FFX, 4FLC
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00206	Lyase_1	24 → 313	Lyase	Domain
  PF10397	ADSL_C	378 → 460	Adenylosuccinate lyase C-terminus	Domain

• Sequence:

  MAAGGDHGSPDSYRSPLASRYASPEMCFVFSDRYKFRTWRQLWLWLAEAEQTLGLPITDE
  QIQEMKSNLENIDFKMAAEEEKRLRHDVMAHVHTFGHCCPKAAGIIHLGATSCYVGDNTD
  LIILRNALDLLLPKLARVISRLADFAKERASLPTLGFTHFQPAQLTTVGKRCCLWIQDLC
  MDLQNLKRVRDDLRFRGVKGTTGTQASFLQLFEGDDHKVEQLDKMVTEKAGFKRAFIITG
  QTYTRKVDIEVLSVLASLGASVHKICTDIRLLANLKEMEEPFEKQQIGSSAMPYKRNPMR
  SERCCSLARHLMTLVMDPLQTASVQWFERTLDDSANRRICLAEAFLTADTILNTLQNISE
  GLVVYPKVIERRIRQELPFMATENIIMAMVKAGGSRQDCHEKIRVLSQQAASVVKQEGGD
  NDLIERIQVDAYFSPIHSQLDHLLDPSSFTGRASQQVQRFLEEEVYPLLKPYESVMKVKA
  ELCL

• Sequence length: 484