NAA60

Chr 16AR

N-alpha-acetyltransferase 60, NatF catalytic subunit

Also known as: HAT4, IBGC9, NAT15, NatF, hNaa60

NCBI Gene: 79903 ENSG00000122390 UniProt: Q9H7X0 OMIM: 614246

The protein is an N-alpha-acetyltransferase that acetylates N-terminal residues of transmembrane proteins and is required for normal chromosomal segregation during cell division. Biallelic mutations cause basal ganglia calcification, idiopathic, 9, an autosomal recessive disorder affecting the brain's basal ganglia structures. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.596), suggesting some tolerance to inactivating mutations.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes an enzyme that localizes to the Golgi apparatus, where it transfers an acetyl group to the N-terminus of free proteins. This enzyme acts on histones, and its activity is important for chromatin assembly and chromosome integrity. Alternative splicing and the use of alternative promoters results in multiple transcript variants. The upstream promoter is located in a differentially methylated region (DMR) and undergoes imprinting; transcript variants originating from this position are expressed from the maternal allele. [provided by RefSeq, Nov 2015]

GeneReviews OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 0.601 OMIM phenotype

Clinical Summary— NAA60

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.52) — some intolerance to loss-of-function variants.

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ClinVar Variants

6 unique Pathogenic / Likely Pathogenic· 25 VUS of 51 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — NAA60

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.60LOEUF

pLI 0.517

Z-score 2.44

OE 0.19 (0.08–0.60)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.93Z-score

OE missense 0.78 (0.67–0.91)

111 obs / 142.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.19 (0.08–0.60)

0≤0.351.4

Missense OE?0.78 (0.67–0.91)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 2 / 10.6Missense obs/exp: 111 / 142.2Syn Z: 0.06

This gene — mechanism propensity

0.6356th %ile

GOF

0.5268th %ile

LOF

0.4037th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

LOF33% of P/LP variants are LoF

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

51 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6

VUS25

Likely Benign5

Benign2

Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	2	4	0	6
Likely Pathogenic	0	0	0	0
VUS	0	25	0	25
Likely Benign	0	2	3	5
Benign	0	2	0	2
Total	2	33	3	38

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

View in ClinVar →

35 pathogenic / likely-pathogenic (of 51) ClinVar copy-number / structural variants overlap NAA60 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →