ASNS

Chr 7

asparagine synthetase (glutamine-hydrolyzing)

Also known as: ASNSD, TS11

NCBI Gene: 440 ENSG00000070669 UniProt: P08243

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.

GeneReviews ResearchSummary from RefSeq, OMIM

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]

GeneReviews ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.74

Clinical Summary— ASNS

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Gene-Disease Validity (ClinGen)

congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

171 unique Pathogenic / Likely Pathogenic· 233 VUS of 845 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — ASNS

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.74LOEUF

pLI 0.000

Z-score 2.62

OE 0.47 (0.30–0.74)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.86Z-score

OE missense 0.70 (0.63–0.79)

220 obs / 312.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.47 (0.30–0.74)

0≤0.351.4

Missense OE?0.70 (0.63–0.79)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 13 / 27.9Missense obs/exp: 220 / 312.4Syn Z: 1.02

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveASNS-related asparagine synthetase deficiencyLOFAR

This gene — mechanism propensity

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

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

845 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic72

Likely Pathogenic99

VUS233

Likely Benign381

Benign27

Conflicting24

Pathogenic

Likely Pathogenic

233

VUS

381

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	63	5	4	0	72
Likely Pathogenic	73	24	2	0	99
VUS	2	206	19	6	233
Likely Benign	1	4	152	224	381
Benign	0	1	24	2	27
Conflicting	—				24
Total	139	240	201	232	836

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

View in ClinVar →

15 pathogenic / likely-pathogenic (of 20) ClinVar copy-number / structural variants overlap ASNS — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →