ASNS

Chr 7AR

asparagine synthetase (glutamine-hydrolyzing)

Also known as: ASNSD, TS11

The protein is asparagine synthetase, which synthesizes the amino acid asparagine from aspartic acid and glutamine. Mutations cause asparagine synthetase deficiency, an autosomal recessive disorder characterized by severe neurological impairment, seizures, and developmental delays typically manifesting in early infancy. The gene is not highly constrained against loss-of-function variants, consistent with the recessive inheritance pattern.

OMIMResearchSummary from RefSeq, OMIM
LOFmechanismARLOEUF 0.741 OMIM phenotype
Clinical SummaryASNS
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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.
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ClinVar Variants
27 unique Pathogenic / Likely Pathogenic· 39 VUS of 100 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.74LOEUF
pLI 0.000
Z-score 2.62
OE 0.47 (0.300.74)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.86Z-score
OE missense 0.70 (0.630.79)
220 obs / 312.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.47 (0.300.74)
00.351.4
Missense OE0.70 (0.630.79)
00.61.4
Synonymous OE0.88
01.21.6
LoF obs/exp: 13 / 27.9Missense obs/exp: 220 / 312.4Syn Z: 1.02
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveASNS-related asparagine synthetase deficiencyLOFAR

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

DN
0.7327th %ile
GOF
0.6736th %ile
LOF
0.2970th %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

100 submitted variants in ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic21
VUS39
Likely Benign25
6
Pathogenic
21
Likely Pathogenic
39
VUS
25
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
0
1
0
6
Likely Pathogenic
21
0
0
0
21
VUS
1
28
4
6
39
Likely Benign
0
2
11
12
25
Benign
0
0
0
0
0
Total2730161891

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
More from ASN high-impact trials.
Allison SJ·Nat Rev Nephrol
2022
ASN guidelines on P values
Verhoef H et al.·Am J Clin Nutr
2022
2021 ASN Virtual Meeting Abstracts
American Society of Neurochemistry·ASN Neuro
2021
Advancing Nephrology: Division Leaders Advise ASN.
Braden GL et al.·Clin J Am Soc Nephrol
2021
Top 5 full-text resultsSearch PubTator3 ↗