NAA10

Chr XX-linkedXLDXLR

N-alpha-acetyltransferase 10, NatA catalytic subunit

Also known as: ARD1, ARD1A, ARD1P, DXS707, LZMS, MAA, MCOPS1, NATD

NCBI Gene: 8260 ENSG00000102030 UniProt: P41227

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 an N-terminal acetyltransferase that functions as the catalytic subunit of the major amino-terminal acetyltransferase A complex. Mutations in this gene are the cause of Ogden syndrome. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2012]

Primary Disease Associations & Inheritance

Microphthalmia, syndromic 1MIM #309800

X-linked

Ogden syndromeMIM #300855

XLDXLR

UniProtN-terminal acetyltransferase deficiency

523

ClinVar variants

183

Pathogenic / LP

0.76

pLI score

Active trials

Clinical Summary— NAA10

⚡

Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.76) — some intolerance to loss-of-function variants.

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ClinVar Variants

183 Pathogenic / Likely Pathogenic· 81 VUS of 523 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

0.52LOEUF

pLI 0.762

Z-score 2.49

OE 0.11 (0.04–0.52)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

2.41Z-score

OE missense 0.33 (0.25–0.44)

33 obs / 101.2 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.11 (0.04–0.52)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.33 (0.25–0.44)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.06

0≤1.21.6

LoF obs/exp: 1 / 9.1Missense obs/exp: 33 / 101.2Syn Z: -0.31

ClinVar Variant Classifications

523 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic158

Likely Pathogenic25

VUS81

Likely Benign48

Benign30

Conflicting16

158

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	8	148	0	158
Likely Pathogenic	1	18	6	0	25
VUS	1	52	28	0	81
Likely Benign	1	3	24	20	48
Benign	0	1	22	7	30
Conflicting	—				16
Total	5	82	228	27	358

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

View in ClinVar →

Protein Context — Lollipop Plot

NAA10 · protein map & ClinVar variants

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

Gene2Phenotype Curations

NAA10-related syndromic developmental disorder

definitive

Monoallelic XLoss Of FunctionAltered Gene Product Structure

Dev. DisordersEye

G2P ↗

missense variantinframe deletion3 prime UTR variantinframe insertionsplice acceptor variant NMD escapingsplice donor variant NMD escapingframeshift variant NMD escaping

NAA10-related syndromic microphthalmia

moderate

Monoallelic X HemizygousLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure, Decreased Gene Product Level

Dev. DisordersEye

G2P ↗

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