NAA60

Chr 16AR

N-alpha-acetyltransferase 60, NatF catalytic subunit

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

NCBI Gene: 79903ENSG00000122390UniProt: Q9H7X0

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]

Primary Disease Associations & Inheritance

Basal ganglia calcification, idiopathic, 9, autosomal recessiveMIM #620786
AR
102
ClinVar variants
41
Pathogenic / LP
0.52
pLI score
0
Active trials
Clinical Summary— NAA60
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.52) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
41 Pathogenic / Likely Pathogenic· 41 VUS of 102 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.
0.60LOEUF
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?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.
0.93Z-score
OE missense 0.78 (0.67–0.91)
111 obs / 142.2 exp
Tolerant

Mild missense constraint

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.0.19 (0.08–0.60)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.78 (0.67–0.91)
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.0.99
0≤1.21.6
LoF obs/exp: 2 / 10.6Missense obs/exp: 111 / 142.2Syn Z: 0.06

ClinVar Variant Classifications

102 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic40
Likely Pathogenic1
VUS41
Likely Benign5
Benign2
40
Pathogenic
1
Likely Pathogenic
41
VUS
5
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
4
34
0
40
Likely Pathogenic
0
0
1
0
1
VUS
0
25
16
0
41
Likely Benign
0
2
0
3
5
Benign
0
2
0
0
2
Total23351389

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

View in ClinVar →

Protein Context — Lollipop Plot

NAA60 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Basal ganglia calcification, idiopathic, 9, autosomal recessive

MIM #620786

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Basal ganglia calcification: 'Fahr's disease'.
Magrinelli F et al.·Pract Neurol
2025Review
NAA60 (HAT4): the newly discovered bi-functional Golgi member of the acetyltransferase family.
Donnarumma F et al.·Clin Epigenetics
2022Review
A Homozygous Variant in NAA60 Is Associated with Primary Familial Brain Calcification.
Chen X et al.·Mov Disord
2024Case report
Understanding brain calcification via N-terminal acetylation at the Golgi apparatus.
Siggervåg A et al.·Brain
2025Review
The Genetic and Phenotypic Spectrum of Primary Brain Calcification in a Large Cohort from China.
Lin Z et al.·Mov Disord
2025Cohort
White matter disorders with cerebral calcification in adulthood.
Chelban V et al.·Handb Clin Neurol
2024Review
Gene Variants Related to Primary Familial Brain Calcification: Perspectives from Bibliometrics and Meta-Analysis.
Yang D et al.·eNeuro
2025Meta-analysis
Microscopy-based Saccharomyces cerevisiae complementation model reveals functional conservation and redundancy of N-terminal acetyltransferases.
Osberg C et al.·Sci Rep
2016Functional
Mutation spectrum and clinical features of MYORG in Iranian patients with Primary Familial Brain Calcification (PFBC).
Soleimani P et al.·Neurol Sci
2025Cohort
Allelic expression patterns of imprinted and non-imprinted genes in cancer cell lines from multiple histologies.
Krushkal J et al.·Clin Epigenetics
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools