NAA15

Chr 4

N-alpha-acetyltransferase 15, NatA auxiliary subunit

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

NCBI Gene: 80155 ENSG00000164134 UniProt: Q9BXJ9

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.

ResearchSummary from RefSeq, OMIM, UniProt

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]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.28

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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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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 OE?0.15 (0.08–0.28)

0≤0.351.4

Missense OE?0.48 (0.43–0.54)

0≤0.61.4

Synonymous OE?0.93

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

This gene — mechanism propensity

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 · LOEUF 0.28 · ClinGen HI: Sufficient evidence for dosage pathogenicity

Literature Evidence

LOFMechanisms of Congenital Heart Disease Caused by NAA15 Haploinsufficiency.1

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

References