ASRGL1

Chr 11

asparaginase and isoaspartyl peptidase 1

Also known as: ALP, ALP1, CRASH

NCBI Gene: 80150 ENSG00000162174 UniProt: Q7L266

The protein functions as an asparaginase and beta-aspartyl-peptidase that catalyzes asparagine breakdown and may contribute to L-aspartate production, which serves as an excitatory neurotransmitter in the brain. Mutations cause asparaginase deficiency, an autosomal recessive disorder presenting with developmental delay, intellectual disability, and seizures typically beginning in infancy or early childhood. The gene shows low constraint against loss-of-function variants, consistent with the recessive inheritance pattern observed clinically.

ResearchSummary from RefSeq, UniProt

Enables asparaginase activity and beta-aspartyl-peptidase activity. Involved in obsolete L-asparagine catabolic process via L-aspartate. Located in cytoplasm. [provided by Alliance of Genome Resources, Jun 2026]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.39

LOEUF

LOF

Mechanism· G2P

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?

1.39LOEUF

pLI 0.000

Z-score 0.67

OE 0.77 (0.45–1.39)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.20Z-score

OE missense 0.96 (0.85–1.08)

177 obs / 184.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.77 (0.45–1.39)

0≤0.351.4

Missense OE?0.96 (0.85–1.08)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 8 / 10.3Missense obs/exp: 177 / 184.8Syn Z: -0.39

Background carrier burden — how many people carry a rare variant somewhere in ASRGL1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

440 rare PASS variants

Rare truncating (LoF)

1 in 1,400

81 rare PASS variants

Rare synonymous (reference)

1 in 180

174 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ASRGL1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 130	1 in 1,300
South Asian	~43k	1 in 110	1 in 1,500
Remaining (unassigned)	~30k	1 in 110	1 in 780
European (Finnish)	~27k	1 in 260	1 in 1,500
Admixed American	~22k	1 in 140	1 in 4,400
African / African American	~21k	1 in 94	1 in 1,400
East Asian	~20k	1 in 170	1 in 1,300
Ashkenazi Jewish	~13k	1 in 310	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 160	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓