ADSL adenylosuccinate lyase [Homo sapiens (human)] - Gene

Summary

Official Symbol: ADSLprovided by HGNC
Official Full Name: adenylosuccinate lyaseprovided by HGNC
Primary source: HGNC:HGNC:291
See related: Ensembl:ENSG00000239900 MIM:608222; AllianceGenome:HGNC:291
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: ASL; AMPS; ASASE
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]
Expression: Ubiquitous expression in lymph node (RPKM 10.5), testis (RPKM 9.0) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 22q13.1

Exon count:: 14

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	22	NC_000022.11 (40346500..40387527)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	22	NC_060946.1 (40817910..40858924)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	22	NC_000022.10 (40742504..40783531)

Chromosome 22 - NC_000022.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Electroclinical features and phenotypic differences in adenylosuccinate lyase deficiency: Long-term follow-up of seven patients from four families and appraisal of the literature.
Title: Electroclinical features and phenotypic differences in adenylosuccinate lyase deficiency: Long-term follow-up of seven patients from four families and appraisal of the literature.
Adenylosuccinate lyase (ADSL) is an EglN2 hydroxylase substrate in triple negative breast cancer.
Title: Prolyl hydroxylase substrate adenylosuccinate lyase is an oncogenic driver in triple negative breast cancer.
ADSL undergoes conformational changes during catalysis which, together with the crystal structure of a hitherto undetermined product bound conformation, explains the molecular origin of disease for several modern human ADSL mutants.
Title: Molecular comparison of Neanderthal and Modern Human adenylosuccinate lyase.
involved in endometrial cancer aggressiveness by regulating expression of killer cell lectin-like receptor C3
Title: Adenylosuccinate lyase enhances aggressiveness of endometrial cancer by increasing killer cell lectin-like receptor C3 expression by fumarate.
Case Report: Malaysian patient compound heterozygous for two novel ADSL mutations giving rise to adenylosuccinate lyase deficiency.
Title: Adenylosuccinate lyase deficiency in a Malaysian patient, with novel adenylosuccinate lyase gene mutations.
Missense mutations in the adenylosuccinate lyase is associated with Adenylosuccinate lyase deficiency, an inborn error of purine metabolism characterized by neurological and physiological symptoms.
Title: Inherent properties of adenylosuccinate lyase could explain S-Ado/SAICAr ratio due to homozygous R426H and R303C mutations.
structural and biochemical characterization data of WT and mutant R303C ADSL by enzyme kinetics, product binding by isothermal titration calorimetry and X-ray crystallography to reveal the effects of the R303C mutation that results in a nonparallel reduction in enzyme activity
Title: Structural and biochemical characterization of human adenylosuccinate lyase (ADSL) and the R303C ADSL deficiency-associated mutation.
Results proved in cultured skin fibroblasts from patients with AICA-ribosiduria and ADSL deficiency that various mutations of ADSL destabilize to various degrees purinosome assembly and found that the ability to form purinosomes correlates with clinical phenotypes of individual ADSL patients.
Title: Mutations of ATIC and ADSL affect purinosome assembly in cultured skin fibroblasts from patients with AICA-ribosiduria and ADSL deficiency.
D-ribose administration in Polish patients with adenylosuccinate lyase deficiency was accompanied by neither reduction in seizure frequency nor growth enhancement.
Title: D-ribose therapy in four Polish patients with adenylosuccinate lyase deficiency: absence of positive effect.
the cases of the only three children diagnosed to date in the United Kingdom with adenylosuccinate lyase deficiency
Title: Adenylosuccinate lyase deficiency in the United Kingdom pediatric population: first three cases.

Submit: New GeneRIF Correction See all GeneRIFs (20)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Adenylosuccinate lyase deficiency MedGen: C0268126 OMIM: 103050 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
A genome-wide association study of northwestern Europeans involves the C-type natriuretic peptide signaling pathway in the etiology of human height variation. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D22S966E (e-PCR)
- UniSTS:150789

RH98333 (e-PCR)
- UniSTS:88844

RH77705 (e-PCR)
- UniSTS:78617

SHGC-84522 (e-PCR)
- UniSTS:102866

RH71398 (e-PCR)
- UniSTS:52717

RH27785 (e-PCR)
- UniSTS:84726

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables (S)-2-(5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido) succinate lyase (fumarate-forming) activity	IBA Inferred from Biological aspect of Ancestor more info
enables (S)-2-(5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido) succinate lyase (fumarate-forming) activity	IDA Inferred from Direct Assay more info	PubMed
enables N6-(1,2-dicarboxyethyl)AMP AMP-lyase (fumarate-forming) activity	IBA Inferred from Biological aspect of Ancestor more info
enables N6-(1,2-dicarboxyethyl)AMP AMP-lyase (fumarate-forming) activity	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in 'de novo' AMP biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in 'de novo' AMP biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in 'de novo' IMP biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in 'de novo' XMP biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in AMP biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in AMP salvage	IEA Inferred from Electronic Annotation more info
involved_in GMP biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in aerobic respiration	IEA Inferred from Electronic Annotation more info
involved_in purine nucleotide biosynthetic process	IC Inferred by Curator more info	PubMed
involved_in response to hypoxia	IEA Inferred from Electronic Annotation more info
involved_in response to muscle activity	IEA Inferred from Electronic Annotation more info
involved_in response to nutrient	IEA Inferred from Electronic Annotation more info
involved_in response to starvation	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: adenylosuccinate lyase

Names: adenylosuccinase

NP_000017.1

EC 4.3.2.2

NP_001116850.1

EC 4.3.2.2

NP_001304852.1

EC 4.3.2.2

NP_001350769.1

EC 4.3.2.2

NP_001397741.1

EC 4.3.2.2

NP_001397743.1

EC 4.3.2.2

NP_001397745.1

EC 4.3.2.2

XP_016884125.1

EC 4.3.2.2

XP_047297124.1

EC 4.3.2.2

XP_054181166.1

EC 4.3.2.2

XP_054181167.1

EC 4.3.2.2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_007993.2 RefSeqGene

Range

5001..27868

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000026.4 → NP_000017.1 adenylosuccinate lyase isoform a

See identical proteins and their annotated locations for NP_000017.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the predominant transcript and encodes the longest isoform (a).

Source sequence(s)

AF067853, AL022238, BG187609, BP298407

Consensus CDS

CCDS14001.1

UniProtKB/Swiss-Prot

B0QY76, O75495, P30566, Q5TI34

UniProtKB/TrEMBL

Q71UA4, X5D8S6

Related

ENSP00000485525.1, ENST00000623063.3

Conserved Domains (1) summary

cd03302
Location:17 → 452

Adenylsuccinate_lyase_2; Adenylsuccinate lyase (ASL)_subgroup 2
NM_001123378.3 → NP_001116850.1 adenylosuccinate lyase isoform b

See identical proteins and their annotated locations for NP_001116850.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks the penultimate, in-frame coding exon compared to variant 1. The resulting isoform (b) is shorter, missing an internal protein segment compared to isoform a.

Source sequence(s)

AF067854, AL022238, BG187609, BP298407

Consensus CDS

CCDS46714.1

UniProtKB/TrEMBL

A8K4X6

Related

ENSP00000341429.6, ENST00000342312.9

Conserved Domains (1) summary

cd03302
Location:17 → 397

Adenylsuccinate_lyase_2; Adenylsuccinate lyase (ASL)_subgroup 2
NM_001317923.2 → NP_001304852.1 adenylosuccinate lyase isoform c

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate donor splice site at the 5' terminal exon, which results in translation initiation from an in-frame, downstream start codon compared to variant 1. The encoded isoform (c) has a shorter N-terminus compared to isoform a.

Source sequence(s)

AF067853, AL022238, BG187609, BP298407, KJ535056

UniProtKB/TrEMBL

Q71UA4

Conserved Domains (1) summary

cd03302
Location:1 → 388

Adenylsuccinate_lyase_2; Adenylsuccinate lyase (ASL)_subgroup 2
NM_001363840.3 → NP_001350769.1 adenylosuccinate lyase isoform d

Status: REVIEWED

Source sequence(s)

AL022238

Consensus CDS

CCDS87029.1

UniProtKB/TrEMBL

A0A1B0GTJ7, A0A1B0GWJ0

Related

ENSP00000490946.1, ENST00000636714.1

Conserved Domains (1) summary

cd03302
Location:17 → 452

Adenylsuccinate_lyase_2; Adenylsuccinate lyase (ASL)_subgroup 2
NM_001410812.1 → NP_001397741.1 adenylosuccinate lyase isoform e

Status: REVIEWED

Source sequence(s)

AL022238

Consensus CDS

CCDS93169.1

UniProtKB/TrEMBL

A0A7P0Z472

Related

ENSP00000505244.1, ENST00000680978.1
NM_001410814.1 → NP_001397743.1 adenylosuccinate lyase isoform f

Status: REVIEWED

Source sequence(s)

AL022238

Consensus CDS

CCDS93171.1

UniProtKB/TrEMBL

A0A7P0T8E4

Related

ENSP00000505155.1, ENST00000679723.1
NM_001410816.1 → NP_001397745.1 adenylosuccinate lyase isoform g

Status: REVIEWED

Source sequence(s)

AL022238

Consensus CDS

CCDS93170.1

UniProtKB/TrEMBL

A0A1B0GTG9

Related

ENSP00000489696.2, ENST00000637666.2

RNA

NR_134256.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (4) uses an alternate donor splice site in the 3' region compared to variant 1. It is represented as non-coding because the use of the 5'-most translational start codon renders this transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AF067853, AL022238, BG187609, BP298407, KJ535020