NAA15

Chr 4AD

N-alpha-acetyltransferase 15, NatA auxiliary subunit

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

NCBI Gene: 80155ENSG00000164134UniProt: Q9BXJ9OMIM: 608000

The protein serves as the auxiliary subunit of the N-terminal acetyltransferase A (NatA) complex, which transfers acetyl groups from acetyl-coenzyme A to the alpha-amino group of nascent polypeptides, a modification essential for normal cell function. Mutations cause autosomal dominant intellectual developmental disorder with behavioral abnormalities through loss-of-function mechanisms. The gene is highly intolerant to loss-of-function variants, consistent with haploinsufficiency as the likely pathogenic mechanism.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.281 OMIM phenotype
Clinical Summary— NAA15
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Gene-Disease Validity (ClinGen)
syndromic intellectual disability · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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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.
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ClinVar Variants
97 unique Pathogenic / Likely Pathogenic· 198 VUS of 404 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

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
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongNAA15-related congenital heart disease and neurodevelopmental disorderLOFAD
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 · 79% 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

404 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic50
Likely Pathogenic47
VUS198
Likely Benign76
Benign8
Conflicting4
50
Pathogenic
47
Likely Pathogenic
198
VUS
76
Likely Benign
8
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
39
0
11
0
50
Likely Pathogenic
38
6
2
1
47
VUS
8
171
16
3
198
Likely Benign
0
4
33
39
76
Benign
0
0
6
2
8
Conflicting
—4
Total851816845383

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

View in ClinVar →

Protein Context — Lollipop Plot

NAA15 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
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
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