NAA15

Chr 4AD

N-alpha-acetyltransferase 15, NatA auxiliary subunit

Also known as: Ga19, MRD50, NARG1, NAT1P, NATH, TBDN, TBDN100

NCBI Gene: 80155ENSG00000164134UniProt: Q9BXJ9

N-alpha-acetylation is among the most common post-translational protein modifications in eukaryotic cells. This process involves the transfer of an acetyl group from acetyl-coenzyme A to the alpha-amino group on a nascent polypeptide and is essential for normal cell function. This gene encodes the auxillary subunit of the N-terminal acetyltransferase A (NatA) complex. [provided by RefSeq, Jan 2017]

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal dominant 50, with behavioral abnormalitiesMIM #617787
AD
1
Active trials
68
Pathogenic / LP
279
ClinVar variants
10
Pubs (1 yr)
3.8
Missense Z· constrained
0.28
LOEUF· LoF intolerant
Clinical Summary— NAA15
🧬
Gene-Disease Validity (ClinGen)
syndromic intellectual disability · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
68 Pathogenic / Likely Pathogenic· 158 VUS of 279 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.28LOEUF
pLI 0.996
Z-score 5.41
OE 0.15 (0.08–0.28)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
3.81Z-score
OE missense 0.48 (0.43–0.54)
202 obs / 422.2 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.15 (0.08–0.28)
0≤0.351.4
Missense OE0.48 (0.43–0.54)
0≤0.61.4
Synonymous OE0.93
0≤1.21.6
LoF obs/exp: 7 / 47.0Missense obs/exp: 202 / 422.2Syn Z: 0.69
LOF
DN
0.4587th %ile
GOF
0.5660th %ile
LOF
0.54top 25%

The Badonyi & Marsh model scores gain-of-function highest, but genomic evidence most strongly supports loss-of-function (haploinsufficiency) as the primary mechanism.

LOF1 literature citation · 43% of P/LP variants are LoF · LOEUF 0.28

Literature Evidence

LOFMechanisms of Congenital Heart Disease Caused by NAA15 Haploinsufficiency.PMID:33557580

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

279 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35
Likely Pathogenic33
VUS158
Likely Benign51
Benign2
35
Pathogenic
33
Likely Pathogenic
158
VUS
51
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
17
0
18
0
35
Likely Pathogenic
12
5
15
1
33
VUS
3
138
15
2
158
Likely Benign
0
1
25
25
51
Benign
0
0
1
1
2
Total321447429279

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

View in ClinVar →

NAA15 · protein map & ClinVar variants

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

Gene2Phenotype Curations

NAA15-related congenital heart disease and neurodevelopmental disorder

strong
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases.
Stessman HA et al.·Nat Genet
2017
Expanding the phenotypic spectrum of NAA10-related neurodevelopmental syndrome and NAA15-related neurodevelopmental syndrome.
Lyon GJ et al.·Eur J Hum Genet
2023
Truncating Variants in NAA15 Are Associated with Variable Levels of Intellectual Disability, Autism Spectrum Disorder, and Congenital Anomalies.
Cheng H et al.·Am J Hum Genet
2018
Possible Catch-Up Developmental Trajectories for Children with Mild Developmental Delay Caused by NAA15 Pathogenic Variants.
Tian Y et al.·Genes (Basel)
2022Review
Naa15 Haploinsufficiency and De Novo Missense Variants Associate With Neurodevelopmental Disorders and Interfere With Neurogenesis and Neuron Development.
He M et al.·Autism Res
2025
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients