GeneBe

NAA10

protein-coding

N-alpha-acetyltransferase 10, NatA catalytic subunit, the group of GCN5 related N-acetyltransferases|N-alpha-acetyltransferase subunits

Gene summary

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]

Previous symbols:
  • ARD1
  • ARD1A

MANE transcript

NM_003491.4

Inheritance

XL

ClinVar variants

P:46U:93B:40

Top phenotype

Ogden syndrome

gnomAD constraint

pLI —, LoF o/e 0.11

Max pathogenic AF

—

Genomic locus

chrX:153,929,225-153,935,080

External References & Databases

Ensembl (ENSG00000102030)NCBI Gene (8260)OMIM (300013)HGNC:18704GenCCUniProt (P41227)AlphaFoldClinVar (NAA10)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~5.9 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Ogden syndromeSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010457

Submitter: Ambry Genetics

microphthalmia, syndromic 1MODERATE

Inheritance Pattern: XL

Disease ID:MONDO:0010671

Submitter: G2P

Ogden syndromeSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010457

Submitter: Labcorp Genetics (formerly Invitae)

NAA10-related syndromeDEFINITIVE

Inheritance Pattern: XL

Disease ID:MONDO:0100124

Submitter: Broad Center for Mendelian Genomics

Ogden syndromeDEFINITIVE

Inheritance Pattern: XL

Disease ID:MONDO:0010457

Submitter: G2P

NAA10-related syndromeSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0100124

Submitter: PanelApp Australia

NAA10-related syndromeDEFINITIVE

Inheritance Pattern: XL

Disease ID:MONDO:0100124

Submitter: ClinGen

*NAA10* was first reported in relation to X-linked *NAA10*-related syndrome in 2011 (Rope et al., PMID: 21700266). *NAA10*-related syndrome is characterized by substantial phenotypic variability, ranging from a severe lethal phenotype in males originally described as Ogden syndrome, to milder forms of intellectual disability in both males and females (PMID: 30054457). Additional findings in some individuals may include growth failure, dysmorphic facial features, hypotonia and/or hypertonia, and cardiac and skeletal abnormalities. Syndromic microphthalmia (Lenz microphthalmia syndrome) has been reported in males with *NAA10* variants resulting in decreased mRNA (splice, frameshift and polyadenylation signal variants) (PMID: 30842225). Numerous unique variants in *NAA10*, mostly missense, have been reported, with some variants occurring *de novo*. Variants in this gene have been reported in at least 22 probands in 6 publications (PMIDs: 21700266, 24431331, 25099252, 26522270, 31127942, 35039925). More evidence is available in the literature, but the maximum score for genetic evidence (12 points) has been reached. *NAA10* encodes the enzyme NAA10, which is the catalytic subunit in the N-terminal acetyltransferase A (NatA) complex. This gene-disease relationship is also supported by protein interaction with NAA15, also involved in syndromic intellectual disability; functional alteration in non-patient cells; and a zebrafish model. In summary, there is definitive evidence supporting the relationship between *NAA10* and X-linked *NAA10*-related syndrome. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on September 2, 2020 (SOP Version 7). As of January 10, 2023, this record underwent administrative updates to include minor edits to the evidence summary text and update scoring to be consistent with SOP Version 9. No new evidence has been added, and the classification remains the same.

microphthalmia, syndromic 1LIMITED

Inheritance Pattern: XL

Disease ID:MONDO:0010671

Submitter: Ambry Genetics

Ogden syndromeSUPPORTIVE

Inheritance Pattern: XL

Disease ID:MONDO:0010457

Submitter: Orphanet

microphthalmia, Lenz typeSUPPORTIVE

Inheritance Pattern: XL

Disease ID:MONDO:0018924

Submitter: Orphanet

microphthalmia, syndromic 1LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0010671

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Ogden syndromeXL

Manifestation: Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic; Renal

Intervention: Cardiovascular

Rationale: Though the overall phenotype may be recognizable, reported individuals have died due to sequelae of arrhythmias, and surveillance and awareness may allow early diagnosis and treatment, which may reduce morbidity and mortality

Refs: 11426460; 21700266; 24431331; 25099252; 26522270; 31127942Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NAA10 variants in ClinVar

14 Conditions Cataloged
not providedTotal: 151
Ogden syndromeTotal: 47
not specifiedTotal: 19
NAA10-related disorderTotal: 17
Microphthalmia, syndromic 1Total: 14
Inborn genetic diseasesTotal: 13
Intellectual disabilityTotal: 6
Neurodevelopmental disorderTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003491.4. 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.

EffectPLPVUSLBBSum
synonymous
5
clinvar
26
clinvar
6
clinvar
 37
missense
11
clinvar
30
clinvar
73
clinvar
7
clinvar
1
clinvar
 122
nonsense
2
clinvar
 2
start loss
0
frameshift
1
clinvar
1
clinvar
1
clinvar
 3
splice donor/acceptor (+/-2bp)
2
clinvar
1
clinvar
12
clinvar
 15
Total143293337179

Highest pathogenic variant AF is 0.0000018217459

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 30 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_003491.4RefSeqNP_003482.18MANE Select
ENST00000464845.6EnsemblENSP00000417763.18MANE Select
NM_001256119.2RefSeqNP_001243048.17Standard
NM_001256120.2RefSeqNP_001243049.18Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
naa10Danio rerio

Structure: ventral mandibular arch

Quality: decreased size

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Leukotriene metabolism
  • Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

Biological Process

  • DNA packaging
  • protein acetylation
  • N-terminal protein amino acid acetylation
  • internal protein amino acid acetylation
  • N-terminal peptidyl-serine acetylation

Molecular Function

  • peptide alpha-N-acetyltransferase activity
  • protein binding
  • N-acetyltransferase activity
  • acetyltransferase activity
  • ribosome binding

Cellular Component

  • nucleus
  • nucleolus
  • cytoplasm
  • cytosol
  • membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000464845
Coding exons
8
Length
5982
Individuals with no LoFs
125714
Homozygous LoFs
1
Heterozygous LoFs
1
Defined
125716
p
0.00000795
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense2.41331010.3260.000008321555
Missense (PolyPhen)222.8560.087503354
Synonymous-0.3084542.41.060.00000372431
Loss of Function2.4919.090.1106.30e-7164

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.0000730.000058rare
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)00.0absent
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Catalytic subunit of the N-terminal acetyltransferase A (NatA) complex which displays alpha (N-terminal) acetyltransferase activity (PubMed:15496142, PubMed:19826488, PubMed:19420222, PubMed:20145209, PubMed:27708256, PubMed:25489052). Acetylates amino termini that are devoid of initiator methionine (PubMed:19420222). The alpha (N-terminal) acetyltransferase activity may be important for vascular, hematopoietic and neuronal growth and development. Without NAA15, displays epsilon (internal) acetyltransferase activity towards HIF1A, thereby promoting its degradation (PubMed:12464182). Represses MYLK kinase activity by acetylation, and thus represses tumor cell migration (PubMed:19826488). Acetylates, and stabilizes TSC2, thereby repressing mTOR activity and suppressing cancer development (PubMed:20145209). Acetylates HSPA1A and HSPA1B at 'Lys-77' which enhances its chaperone activity and leads to preferential binding to co-chaperone HOPX (PubMed:27708256). Acts as a negative regulator of sister chromatid cohesion during mitosis (PubMed:27422821). {ECO:0000269|PubMed:12464182, ECO:0000269|PubMed:15496142, ECO:0000269|PubMed:19420222, ECO:0000269|PubMed:19826488, ECO:0000269|PubMed:20145209, ECO:0000269|PubMed:25489052, ECO:0000269|PubMed:27422821, ECO:0000269|PubMed:27708256}.;
Disease
DISEASE: N-terminal acetyltransferase deficiency (NATD) [MIM:300855]: An enzymatic deficiency resulting in postnatal growth failure with severe delays and dysmorphic features. It is clinically characterized by wrinkled forehead, prominent eyes, widely opened anterior and posterior fontanels, downsloping palpebral fissures, thickened lids, large ears, flared nares, hypoplastic alae, short columella, protruding upper lip, and microretrognathia. There are also delayed closing of fontanels and broad great toes. Skin is characterized by redundancy or laxity with minimal subcutaneous fat, cutaneous capillary malformations, and very fine hair and eyebrows. Death results from cardiogenic shock following arrhythmia. {ECO:0000269|PubMed:21700266, ECO:0000269|PubMed:25489052, ECO:0000269|PubMed:26522270}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Microphthalmia, syndromic, 1 (MCOPS1) [MIM:309800]: A rare syndrome defined by the canonical features of unilateral or bilateral microphthalmia or anophthalmia and defects in the skeletal and genitourinary systems. Microphthalmia is a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities. Anomalies of the digits, teeth, and ears are hallmarks of MCOPS1. Intellectual disability ranges from mild to severe, with self-mutilating behaviors and seizures in severely affected MCOPS1 individuals. {ECO:0000269|PubMed:24431331}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.281

Intolerance Scores

LoFtool
0.309
RVIS EVS
-0.03
RVIS percentile EVS
51.04

Essentials

Essential (CRISPR)
E
Essential (CRISPR2)
E
Essential (gene trap)
E
Indispensability pred.
E
Indispensability score
0.824
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