ASL

Chr 7AR

argininosuccinate lyase

Also known as: ASAL, ASLD

NCBI Gene: 435ENSG00000126522UniProt: P04424

This gene encodes a member of the lyase 1 family. The encoded protein forms a cytosolic homotetramer and primarily catalyzes the reversible hydrolytic cleavage of argininosuccinate into arginine and fumarate, an essential step in the liver in detoxifying ammonia via the urea cycle. Mutations in this gene result in the autosomal recessive disorder argininosuccinic aciduria, or argininosuccinic acid lyase deficiency. A nontranscribed pseudogene is also located on the long arm of chromosome 22. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Argininosuccinic aciduriaMIM #207900
AR
992
ClinVar variants
76
Pathogenic / LP
0.00
pLI score
12
Active trials
Clinical Summary— ASL
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
76 Pathogenic / Likely Pathogenic· 82 VUS of 992 total submissions
💊
Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.94LOEUF
pLI 0.000
Z-score 1.83
OE 0.64 (0.44–0.94)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.75Z-score
OE missense 0.87 (0.79–0.97)
247 obs / 282.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.64 (0.44–0.94)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.87 (0.79–0.97)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.16
0≤1.21.6
LoF obs/exp: 19 / 29.8Missense obs/exp: 247 / 282.4Syn Z: -1.37

ClinVar Variant Classifications

992 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic59
VUS82
Likely Benign306
Benign16
Conflicting4
17
Pathogenic
59
Likely Pathogenic
82
VUS
306
Likely Benign
16
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
3
7
0
17
Likely Pathogenic
27
25
7
0
59
VUS
0
57
18
7
82
Likely Benign
0
2
158
146
306
Benign
0
0
16
0
16
Conflicting
—4
Total3487206153484

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ASL · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

ASL-related argininosuccinate lyase deficiency

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkin
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Argininosuccinic aciduria

MIM #207900

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Recommended implementation of arterial spin-labeled perfusion MRI for clinical applications: A consensus of the ISMRM perfusion study group and the European consortium for ASL in dementia.
Alsop DC et al.·Magn Reson Med
2015Review
Acute subglottic laryngitis. Etiology, epidemiology, pathogenesis and clinical picture.
Mazurek H et al.·Adv Respir Med
2019Guideline
Current state and guidance on arterial spin labeling perfusion MRI in clinical neuroimaging.
Lindner T et al.·Magn Reson Med
2023
Argininosuccinate lyase deficiency.
Nagamani SC et al.·Genet Med
2012Review
Myocardial arterial spin labeling.
Kober F et al.·J Cardiovasc Magn Reson
2016Review
Renal perfusion imaging by MRI.
Zhang JL et al.·J Magn Reson Imaging
2020Review
MRI of Cerebellar Infarction.
De Cocker LJ et al.·Eur Neurol
2017Review
Consensus-based technical recommendations for clinical translation of renal ASL MRI.
Nery F et al.·MAGMA
2020
Arterial Spin Labeling Perfusion Imaging.
Taso M et al.·Magn Reson Imaging Clin N Am
2024Review
mRNA therapy corrects defective glutathione metabolism and restores ureagenesis in preclinical argininosuccinic aciduria.
Gurung S et al.·Sci Transl Med
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Taurine is a natural suppressor of urea cycle via targeting ASL.
Rao K et al.·Cell Death Discov
2026🔓 Open Access
Similarity of Biological Information Captured by [68]Ga-PSMA-11 PET and ASL Perfusion MRI in Glioblastoma.
Han Y et al.·AJNR Am J Neuroradiol
2026
Multimodal imaging and machine learning for diagnosis of Parkinson's disease with cognitive impairment: ASL and QSM as potential biomarkers.
Qi W et al.·Front Aging Neurosci
2026🔓 Open Access
Effect of acupuncture Baihui acupoint-Yintang acupoint-Neiguan acupoint combined with conventional Western medicine treatment on cerebral blood flow in insomnia patients: a 3D-ASL functional magnetic resonance imaging study.
Wang W et al.·Front Neurol
2026🔓 Open AccessCohort
Time-intensity Profiles and T1-corrected Arterial Transit Time from Multi-delay Pseudo-continuous ASL with a Variable-TR Scheme for the Characterization of Adult-type Diffuse Glioma.
Yamashita K et al.·Clin Neuroradiol
2026
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
CadasilBlood Brain Barrier Defect

MRI Study of Blood-brain Barrier Function in CADASIL

RECRUITING
NCT05902039Peking University First HospitalStarted 2021-04-01
MRI
Chronic Kidney Diseases

Dapagliflozin on Renal Morphology and Renal Perfusion in Patients One Year After Kidney Transplantation

RECRUITING
NCT06560801Phase PHASE4University of Erlangen-Nürnberg Medical SchoolStarted 2023-07-28
Dapagliflozin 10mg Tab
BRCA1 MutationBRCA2 Mutation

BRCA Mutation Carriers' Platform a Multicenter Study

RECRUITING
NCT07253051Fondazione Policlinico Universitario Agostino Gemelli IRCCSStarted 2025-04-05
Registration of clinical datas in the platform
Leiomyosarcoma of OvarySoft Tissue Sarcoma

Trial in Patients With Metastatic or Locally Advanced Leiomyosarcoma

RECRUITING
NCT04383119Phase PHASE2Italian Sarcoma GroupStarted 2021-10-29
TrabectedinGemcitabineNo Intervention: Observational Cohort
Trigeminal Neuralgia (TN)

Magnetic Resonance Imaging in Patients with Trigeminal Neuralgia

NOT YET RECRUITING
NCT06853119Tongji HospitalStarted 2025-03-10
Bariatric Surgery and Physical ActivityObesity/TherapyBariatric Surgery Complications

Impact of a Perioperative Physical Exercise and Respiratory Physiotherapy Program on the Patient Undergoing Bariatric Surgery

RECRUITING
NCT06987903Phase NAFundacin Biomedica Galicia SurStarted 2025-05-07
Pre- and post-operative physical exercise programmePre- and post-operative respiratory physiotherapy
Metastatic Castration-sensitive Prostate Cancer

A Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for the Treatment of Participants With Deleterious Germline or Somatic Homologous Recombination Repair (HRR) Gene-Mutated Metastatic Castration-Sensitive Prostate Cancer (mCSPC)

ACTIVE NOT RECRUITING
NCT04497844Phase PHASE3Janssen Research & Development, LLCStarted 2020-09-23
NiraparibAbiraterone acetate (AA)Prednisone
Migraine

Dietary Intervention for Migraine Relief

NOT YET RECRUITING
NCT07360405Phase NAAmerican UniversityStarted 2026-01
Dietary training
Carcinoma, Non-Small-Cell Lung

A Study of Clinical Outcomes in Participants With EGFR Mutated Advanced Non-Small Cell Lung Cancer (NSCLC) in a Real-World Setting

RECRUITING
NCT07230691Janssen Research & Development, LLCStarted 2025-12-03
Obesity, ChildhoodChild Development

El Sendero: Pathways to Health Study

ENROLLING BY INVITATION
NCT05551650University of Southern CaliforniaStarted 2021-09-01
Glioma

Clinical Study for the Safety and Therapeutic Efficacy of the AI-QMMM Designed TamavaqTM Personalised Vaccine in Patients With Newly Diagnosed Glioma.

RECRUITING
NCT07077616Phase EARLY_PHASE1Biogenea Pharmaceuticals Ltd.Started 2025-07-01
Biological: personalized vaccine Based on genetic and transcriptional sequencing information, personalized peptide vaccines would be designed and produced;
Cancer RiskBreast Cancer RiskLung Cancer (NSCLC)

Development of New Methodologies and Innovative Tools for the diagnoSi and Therapeutic Treatment of uMAni Epithelial Tumors

RECRUITING
NCT06939049ASL LecceStarted 2017-05-02

External Resources

Links to major genomics databases and tools