NAT8L

Chr 4AR

N-acetyltransferase 8 like

Also known as: CML3, NACED, NAT8-LIKE

This gene encodes the neuron-specific N-acetyltransferase that catalyzes the synthesis of N-acetylaspartate (NAA) from L-aspartate and acetyl-CoA, with NAA serving as a major storage and transport form of acetyl-CoA in the nervous system. Mutations cause N-acetylaspartate deficiency (hypoacetylaspartia) with autosomal recessive inheritance. The gene is highly constrained against loss-of-function variants (pLI 0.86, LOEUF 0.46), indicating that such mutations are likely to have significant functional consequences.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

?N-acetylaspartate deficiencyMIM #614063
AR
0
Active trials
8
Pubs (1 yr)
140
P/LP submissions
0%
P/LP missense
0.46
LOEUF
Mechanism
Clinical SummaryNAT8L
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Gene-Disease Validity (ClinGen)
N-acetylaspartate deficiency · ARLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.86) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
140 unique Pathogenic / Likely Pathogenic· 76 VUS of 233 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.46LOEUF
pLI 0.865
Z-score 2.37
OE 0.00 (0.000.46)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.15Z-score
OE missense 0.49 (0.400.60)
69 obs / 140.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.00 (0.000.46)
00.351.4
Missense OE0.49 (0.400.60)
00.61.4
Synonymous OE1.13
01.21.6
LoF obs/exp: 0 / 6.5Missense obs/exp: 69 / 140.7Syn Z: -0.81

ClinVar Variant Classifications

233 submitted variants in ClinVar

Classification Summary

Pathogenic134
Likely Pathogenic6
VUS76
Likely Benign13
Benign3
134
Pathogenic
6
Likely Pathogenic
76
VUS
13
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
134
0
134
Likely Pathogenic
0
0
6
0
6
VUS
1
61
13
1
76
Likely Benign
0
3
2
8
13
Benign
0
0
1
2
3
Total16415611232

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

View in ClinVar →

Protein Context — Lollipop Plot

NAT8L · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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