ASNS

Chr 7AR

asparagine synthetase (glutamine-hydrolyzing)

Also known as: ASNSD, TS11

NCBI Gene: 440ENSG00000070669UniProt: P08243

The protein encoded by this gene is involved in the synthesis of asparagine. This gene complements a mutation in the temperature-sensitive hamster mutant ts11, which blocks progression through the G1 phase of the cell cycle at nonpermissive temperature. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, May 2010]

Primary Disease Associations & Inheritance

Asparagine synthetase deficiencyMIM #615574
AR
591
ClinVar variants
119
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ASNS
🧬
Gene-Disease Validity (ClinGen)
congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome · 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
119 Pathogenic / Likely Pathogenic· 181 VUS of 591 total submissions

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.
0.74LOEUF
pLI 0.000
Z-score 2.62
OE 0.47 (0.30–0.74)
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.
1.86Z-score
OE missense 0.70 (0.63–0.79)
220 obs / 312.4 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.0.47 (0.30–0.74)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.70 (0.63–0.79)
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.0.88
0≤1.21.6
LoF obs/exp: 13 / 27.9Missense obs/exp: 220 / 312.4Syn Z: 1.02

ClinVar Variant Classifications

591 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic61
Likely Pathogenic58
VUS181
Likely Benign277
Benign2
Conflicting12
61
Pathogenic
58
Likely Pathogenic
181
VUS
277
Likely Benign
2
Benign
12
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
39
3
19
0
61
Likely Pathogenic
35
10
13
0
58
VUS
0
156
19
6
181
Likely Benign
1
3
109
164
277
Benign
0
0
1
1
2
Conflicting
—12
Total75172161171591

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

View in ClinVar →

Protein Context — Lollipop Plot

ASNS · protein map & ClinVar variants

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

Gene2Phenotype Curations

ASNS-related asparagine synthetase deficiency

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Asparagine synthetase deficiency

MIM #615574

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — ASNS
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Asparagine synthetase chemotherapy.
Richards NG et al.·Annu Rev Biochem
2006Review
CCT196969 inhibits TNBC by targeting the HDAC5/RXRA/ASNS axis to down-regulate asparagine synthesis.
Yuan Q et al.·J Exp Clin Cancer Res
2025
Myeloid/natural killer (NK) cell precursor acute leukemia as a distinct leukemia type.
Nishimura A et al.·Sci Adv
2023
A novel variant in ASNS gene responsible for syndromic intellectual disability and microcephaly: Case report and literature review.
Jahanpanah M et al.·Mol Genet Genomic Med
2024Review
Critical assessment of variant prioritization methods for rare disease diagnosis within the rare genomes project.
Stenton SL et al.·Hum Genomics
2024
A novel compound heterozygous missense mutation in ASNS broadens the spectrum of asparagine synthetase deficiency.
Wang C et al.·Mol Genet Genomic Med
2020Review
Multi-omics analyses were combined to construct ubiquitination-related features in colon adenocarcinoma and identify ASNS as a novel biomarker.
Wang Z et al.·Front Immunol
2024
AURKA emerges as a vulnerable target for KEAP1-deficient non-small cell lung cancer by activation of asparagine synthesis.
Deng B et al.·Cell Death Dis
2024
Targeting Asparagine Synthetase in Tumorgenicity Using Patient-Derived Tumor-Initiating Cells.
Nishikawa G et al.·Cells
2022
Asparaginase pharmacology: challenges still to be faced.
Lanvers-Kaminsky C·Cancer Chemother Pharmacol
2017Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools