ASL

Chr 7AR

argininosuccinate lyase

Also known as: ASAL, ASLD

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]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Argininosuccinic aciduriaMIM #207900
AR

Clinical highlights

Gene-disease validity (ClinGen)
argininosuccinic aciduria · ARDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
12
Active trials
804
Pubs (1 yr)
P/LP submissions
P/LP missense
0.94
LOEUF
LOF
Mechanism· G2P
📖
GeneReview available — ASL
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.94LOEUF
pLI 0.000
Z-score 1.83
OE 0.64 (0.440.94)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
0.75Z-score
OE missense 0.87 (0.790.97)
247 obs / 282.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.64 (0.440.94)
00.351.4
Missense OE?0.87 (0.790.97)
00.61.4
Synonymous OE?1.16
01.21.6
LoF obs/exp: 19 / 29.8Missense obs/exp: 247 / 282.4Syn Z: -1.37

ClinVar Variant Classifications

0 submitted variants 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.

VCEP specificationsUrea Cycle DisordersReleased
Panel ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

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
Niraparib+ Abiraterone acetate fixed dose combination (FDC)Abiraterone acetate (AA)Prednisone
AMDnAMDWet Age-related Macular Degeneration

Pivotal 2 Study of RGX-314 Gene Therapy in Participants With nAMD

ACTIVE NOT RECRUITING
NCT05407636Phase PHASE3AbbVieStarted 2022-01-13
ABBV-RGX-314 Dose 1ABBV-RGX-314 Dose 2Aflibercept (EYLEA®)
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
Healthy AgingMiddle-aged and Older Adults

Peanut Butter and Brain Health

NOT YET RECRUITING
NCT07774546Phase NAPenn State UniversityStarted 2026-09
Peanut butter
Alzheimer DiseaseDementia

Apolipoprotein E (APOE) Genotype Effects on Triglycerides and Blood Flow in the Human Brain

ACTIVE NOT RECRUITING
NCT04692441Phase NAUniversity of WashingtonStarted 2021-05-01
Heavy Cream
Trigeminal Neuralgia (TN)

Magnetic Resonance Imaging in Patients with Trigeminal Neuralgia

NOT YET RECRUITING
NCT06853119Tongji HospitalStarted 2025-03-10
Urothelial Cancer

A Study of Erdafitinib Compared With Vinflunine or Docetaxel or Pembrolizumab in Participants With Advanced Urothelial Cancer and Selected Fibroblast Growth Factor Receptor (FGFR) Gene Aberrations

ACTIVE NOT RECRUITING
NCT03390504Phase PHASE3Janssen Research & Development, LLCStarted 2018-03-23
ErdafitinibVinflunineDocetaxel
Homeostatic Iron Regulator Gene-related Hereditary Hemochromatosis

Efficacy and Safety of Vamifeport in Adult Participants With Homeostatic Iron Regulator Gene (HFE)-Related Hereditary Hemochromatosis

RECRUITING
NCT07332091Phase PHASE2CSL BehringStarted 2026-01-22
VamifeportPlacebo
B-Cell Non-Hodgkin Lymphoma (NHL)

Biological Analysis of MABs in NHL in a Translational Prospective Observational Study Within Italian Clinical Practice

NOT YET RECRUITING
NCT07767799Fondazione Italiana Linfomi - ETSStarted 2026-10
WP1 - Task 1 - Liquid analysesWP1 - Task 2 - Immunological analysesWP1 - Task 3 - Tumor tissue analyses
Duchenne Muscular Dystrophy

Development of a Registry to Assess Natural History in Duchenne Muscular Dystrophy

NOT YET RECRUITING
NCT06579859Fondazione Policlinico Universitario Agostino Gemelli IRCCSStarted 2024-11-01
Urea Cycle DisordersCarbamoyl-Phosphate Synthase I Deficiency

Study of LNP.UCD.ABE in Patients With Urea Cycle Disorders

RECRUITING
NCT07667387Phase PHASE1, PHASE2Rebecca Ahrens-NicklasStarted 2026-08-07
LNP.UCD.ABE
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