NAA60

protein-coding

N-alpha-acetyltransferase 60, NatF catalytic subunit, the group of GCN5 related N-acetyltransferases|N-alpha-acetyltransferase subunits

Gene summary

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]

Previous symbols:

NAT15

MANE transcript

NM_001083601.3

Inheritance

ClinVar variants

P:6U:28B:6

Top phenotype

Basal ganglia calcification, idiopathic, 9, autosomal recessive

gnomAD constraint

pLI —, LoF o/e 0.19

Max pathogenic AF

—

Genomic locus

chr16:3,443,649-3,486,953

External References & Databases

Ensembl (ENSG00000122390)

Transcript & Mutation Effects

hg38 • Region Span ~43.3 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

basal ganglia calcification, idiopathic, 9, autosomal recessiveMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0968977

Submitter: Ambry Genetics

basal ganglia calcification, idiopathic, 9, autosomal recessiveSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0968977

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Basal ganglia calcification, idiopathic, 9, autosomal recessiveAR

Manifestation: Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 38480682

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NAA60 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 26

Basal ganglia calcification, idiopathic, 9, autosomal recessiveTotal: 6

not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001083601.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	3 clinvar	1 clinvar	6
missense	4 clinvar		26 clinvar	1 clinvar	1 clinvar	32
nonsense						0
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)	1 clinvar					1
Total	6	0	28	4	2	40

Highest pathogenic variant AF is 0.000020447667

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 47 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001083601.3	RefSeq	NP_001077070.1	5	MANE Select
ENST00000407558.9	Ensembl	ENSP00000385903.4	5	MANE Select
NM_001083600.3	RefSeq	NP_001077069.1	5	Standard
NM_001317093.1	RefSeq	NP_001304022.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

nucleosome assembly
N-terminal protein amino acid acetylation
chromosome segregation
cell population proliferation
N-terminal peptidyl-methionine acetylation

Molecular Function

peptide alpha-N-acetyltransferase activity
H4 histone acetyltransferase activity
protein homodimerization activity

Cellular Component

Golgi membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000407558
Coding exons: 5
Length: 43353
Individuals with no LoFs: 124630
Homozygous LoFs: 0
Heterozygous LoFs: 9
Defined: 124639
p: 0.0000361

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.929	111	142	0.781	0.00000813	1577
Missense (PolyPhen)		13	39.609	0.32821		458
Synonymous	0.0606	59	59.6	0.990	0.00000400	452
Loss of Function	2.44	2	10.6	0.189	5.12e-7	127

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000065	0.000065	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000095	0.000093	rare
European (Non-Finnish)	0.000037	0.000035	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: N-alpha-acetyltransferase that specifically mediates the acetylation of N-terminal residues of the transmembrane proteins, with a strong preference for N-termini facing the cytosol (PubMed:25732826). Displays N-terminal acetyltransferase activity towards a range of N-terminal sequences including those starting with Met-Lys, Met-Val, Met-Ala and Met-Met (PubMed:21750686, PubMed:25732826, PubMed:27550639, PubMed:27320834). Required for normal chromosomal segregation during anaphase (PubMed:21750686). May also show histone acetyltransferase activity; such results are however unclear in vivo and would require additional experimental evidences (PubMed:21981917). {ECO:0000269|PubMed:21750686, ECO:0000269|PubMed:25732826, ECO:0000269|PubMed:27320834, ECO:0000269|PubMed:27550639, ECO:0000305|PubMed:21981917}.;

Recessive Scores

pRec: 0.0989

Intolerance Scores

RVIS EVS: -0.23
RVIS percentile EVS: 37.11

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium