ASL

Chr 7AR

argininosuccinate lyase

Also known as: ASAL, ASLD

The protein catalyzes the reversible hydrolytic cleavage of argininosuccinate into arginine and fumarate as an essential step in the urea cycle for ammonia detoxification. Mutations cause argininosuccinic aciduria, an autosomal recessive disorder resulting from argininosuccinic acid lyase deficiency.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, Mechanism
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
24 unique Pathogenic / Likely Pathogenic· 22 VUS of 200 total submissions
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Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available
📖
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 OE0.64 (0.440.94)
00.351.4
Missense OE0.87 (0.790.97)
00.61.4
Synonymous OE1.16
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

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

200 submitted variants in ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic19
VUS22
Likely Benign140
Benign13
Conflicting1
5
Pathogenic
19
Likely Pathogenic
22
VUS
140
Likely Benign
13
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
1
3
0
5
Likely Pathogenic
10
8
1
0
19
VUS
0
17
4
1
22
Likely Benign
0
0
72
68
140
Benign
0
0
13
0
13
Conflicting
1
Total11269369200

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

AMDnAMDWet Age-related Macular Degeneration

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

RECRUITING
NCT05407636Phase PHASE3AbbVieStarted 2022-01-13
ABBV-RGX-314 Dose 1ABBV-RGX-314 Dose 2Aflibercept (EYLEA®)
Migraine

Dietary Intervention for Migraine Relief

NOT YET RECRUITING
NCT07360405Phase NAAmerican UniversityStarted 2026-01
Dietary training
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
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
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
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
Alzheimer DiseaseDementia

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

RECRUITING
NCT04692441Phase NAUniversity of WashingtonStarted 2021-05-01
Heavy Cream
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
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
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
Obesity, ChildhoodChild Development

El Sendero: Pathways to Health Study

ENROLLING BY INVITATION
NCT05551650University of Southern CaliforniaStarted 2021-09-01
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
Clinical Literature
Open Research Assistant →