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…
LOFmechanismARLOEUF 0.941 OMIM phenotype
VCEP Guidelines: Urea Cycle DisordersReleased
ClinGen Panel
Clinical SummaryASL
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Gene-Disease Validity (ClinGen)
argininosuccinic aciduria · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
44 unique Pathogenic / Likely Pathogenic· 62 VUS of 197 total submissions
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Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available
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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
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveASL-related argininosuccinate lyase deficiencyLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.74top 25%
GOF
0.6150th %ile
LOF
0.3358th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

197 submitted variants in ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic34
VUS62
Likely Benign72
Benign3
10
Pathogenic
34
Likely Pathogenic
62
VUS
72
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
2
3
0
10
Likely Pathogenic
16
18
0
0
34
VUS
0
45
11
6
62
Likely Benign
0
0
57
15
72
Benign
0
0
3
0
3
Total21657421181

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

View in ClinVar →

3 pathogenic / likely-pathogenic (of 3) ClinVar copy-number / structural variants overlap ASL — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

ASL · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Low-grade NMIBCFGFR Gene AmplificationFGFR Gene Alterations

Efficacy and Safety of TYRA-300 in Participants With FGFR3 Altered Low Grade, Intermediate Risk Non-Muscle Invasive Bladder Cancer

RECRUITING
NCT06995677Phase PHASE2Tyra Biosciences, IncStarted 2025-06-27
TYRA-300 60mgTYRA-300 50mgTYRA-300 Dose TBD
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
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
Brain Insulin-sensitivityBrain Vascular FunctionCerebral Blood Flow

Effects of Wild Blueberry Consumption on Brain Function in Elderly

RECRUITING
NCT07177781Phase NAMaastricht University Medical CenterStarted 2024-12-05
Wild blueberry powder
Urea Cycle DisordersCarbamoyl-Phosphate Synthase I Deficiency

A Phase I/II Open-label Safety and Efficacy Study of LNP.UCD.ABE in Patients With Urea Cycle Disorders.

NOT YET RECRUITING
NCT07667387Phase PHASE1, PHASE2Rebecca Ahrens-NicklasStarted 2026-07
LNP.UCD.ABE
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
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
Carcinoma, Intraductal, NoninfiltratingRecurrence, Local NeoplasmBreast Neoplasms

Trial of Low Dose Tamoxifen in Women With Breast Intraepithelial Neoplasia - Long Term Follow-up

ACTIVE NOT RECRUITING
NCT01357772Phase PHASE3Andrea DeCensiStarted 2008-11-12
Tamoxifenplacebo
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
Non-Small Cell Lung Cancer

Double Blind Placebo Controlled Controlled Study of Adjuvant MEDI4736 In Completely Resected NSCLC

ACTIVE NOT RECRUITING
NCT02273375Phase PHASE3Canadian Cancer Trials GroupStarted 2015-02-24
MEDI4736Placebo
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