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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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ASRGL1
asparaginase and isoaspartyl peptidase 1
Chromosome 11 · 11q12.3
NCBI Gene: 80150Ensembl: ENSG00000162174.13HGNC: HGNC:16448UniProt: A0A024R573
40PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Protease
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
N4-(beta-N-acetylglucosaminyl)-L-asparaginase activityasparaginase activitybeta-aspartyl-peptidase activitycytoplasmRetinal dystrophyinherited retinal dystrophyneuroinflammatory disorderexostosis
✦AI Summary

ASRGL1 (asparaginase and isoaspartyl peptidase 1) is a dual-function enzyme that catalyzes the hydrolysis of L-asparagine to L-aspartic acid and ammonia, while also cleaving isoaspartyl dipeptides that can alter protein folding 1. The enzyme requires autocatalytic processing between G167 and T168 for activation, with oligomerization being critical for this process and enzymatic activity 1. ASRGL1 plays essential roles in neuronal function and retinal health, as it prevents TDP-43 protein aggregation by cleaving isoaspartates that make TDP-43 prone to misfolding 2. Loss of ASRGL1 function causes autosomal recessive retinal degeneration, with the G178R mutation leading to photoreceptor loss and progressive vision impairment 34. In disease contexts, ASRGL1 expression is diminished in ALS brain samples, contributing to TDP-43 proteinopathy and neurodegeneration 2. Conversely, ASRGL1 is overexpressed in various cancers including hepatocellular carcinoma, nasopharyngeal carcinoma, and endometrial cancer, where it promotes cell proliferation, invasion, and poor prognosis through cell cycle regulation and metabolic reprogramming 567. These findings highlight ASRGL1's dual role as both a neuroprotective enzyme and a potential oncogene depending on cellular context.

Sources cited
1
ASRGL1 catalyzes hydrolysis of L-asparagine and isoaspartyl dipeptides, requires autocatalytic processing for activation
PMID: 32434038
2
ASRGL1 prevents TDP-43 aggregation by cleaving isoaspartates, and is diminished in ALS brain samples
PMID: 38755145
3
G178R mutation in ASRGL1 causes autosomal recessive retinal degeneration
PMID: 27106100
4
Mouse model confirms ASRGL1 mutations cause retinal degeneration with cone and rod photoreceptor loss
PMID: 36011372
5
ASRGL1 overexpression in hepatocellular carcinoma promotes proliferation through CDK1-dependent cell cycle regulation
PMID: 36572570
6
ASRGL1 promotes nasopharyngeal carcinoma invasion and metabolic reprogramming
PMID: 40320045
7
Low ASRGL1 expression correlates with poor survival in endometrial cancer
PMID: 38972163
Disease Associationsⓘ20
Retinal dystrophyOpen Targets
0.41Moderate
inherited retinal dystrophyOpen Targets
0.37Weak
neuroinflammatory disorderOpen Targets
0.24Weak
exostosisOpen Targets
0.16Weak
hypertrophic cardiomyopathyOpen Targets
0.12Weak
cardiovascular diseaseOpen Targets
0.11Weak
hepatocellular carcinomaOpen Targets
0.11Weak
strokeOpen Targets
0.11Weak
neoplasmOpen Targets
0.10Weak
metabolic syndromeOpen Targets
0.10Suggestive
Alzheimer diseaseOpen Targets
0.10Suggestive
cancerOpen Targets
0.10Suggestive
chronic kidney diseaseOpen Targets
0.10Suggestive
osteoporosisOpen Targets
0.10Suggestive
breast cancerOpen Targets
0.09Suggestive
Parkinson diseaseOpen Targets
0.09Suggestive
infectionOpen Targets
0.09Suggestive
Marchiafava-Bignami DiseaseOpen Targets
0.09Suggestive
hypertensionOpen Targets
0.09Suggestive
periodontitisOpen Targets
0.08Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
GOT1L1Protein interaction96%IL4I1Protein interaction93%ADSS1Protein interaction93%ADSS2Protein interaction92%ASNSProtein interaction92%ASPAProtein interaction92%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
98%
Lung
31%
Liver
10%
Heart
4%
Ovary
4%
Gene Interaction Network
Click a node to explore
ASRGL1GOT1L1IL4I1ADSS1ADSS2ASNSASPA
PROTEIN STRUCTURE
Preparing viewer…
PDB4O0C · 1.50 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.12LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.74 [0.50–1.12]
RankingsWhere ASRGL1 stands among ~20K protein-coding genes
  • #10,133of 20,598
    Most Researched40
  • #11,556of 17,882
    Most Constrained (LOEUF)1.12
Genes detectedASRGL1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
TDP-43 proteinopathy in ALS is triggered by loss of ASRGL1 and associated with HML-2 expression.
PMID: 38755145
Nat Commun · 2024
1.00
2
A Mouse Model with Ablated Asparaginase and Isoaspartyl Peptidase 1 (
PMID: 36011372
Genes (Basel) · 2022
0.90
3
Single-cell transcriptomics and metabolomics reveal the potential role of ASRGL1 in metabolic reprogramming and invasion of nasopharyngeal carcinoma cells.
PMID: 40320045
Int J Biochem Cell Biol · 2025
0.80
4
Metabolic classifications of renal cell carcinoma reveal intrinsic connections with clinical and immune characteristics.
PMID: 36829161
J Transl Med · 2023
0.70
5
Asparaginase-like protein 1 as a prognostic tissue biomarker in clinicopathologically and molecularly characterized endometrial cancer.
PMID: 38972163
Eur J Obstet Gynecol Reprod Biol · 2024
0.60