NAA20

protein-coding

N-alpha-acetyltransferase 20, NatB catalytic subunit, the group of GCN5 related N-acetyltransferases|N-alpha-acetyltransferase subunits

Gene summary

NAT5 is a component of N-acetyltransferase complex B (NatB). Human NatB performs cotranslational N(alpha)-terminal acetylation of methionine residues when they are followed by asparagine (Starheim et al., 2008 [PubMed 18570629]).[supplied by OMIM, Apr 2009]

Previous symbols:

NAT5

MANE transcript

NM_016100.5

Inheritance

ClinVar variants

P:3U:22B:3

Top phenotype

Intellectual developmental disorder, autosomal recessive 73

gnomAD constraint

pLI —, LoF o/e 0.49

Max pathogenic AF

—

Genomic locus

chr20:20,017,310-20,033,655

External References & Databases

Ensembl (ENSG00000173418)

Transcript & Mutation Effects

hg38 • Region Span ~16.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

intellectual developmental disorder, autosomal recessive 73LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0030533

Submitter: Ambry Genetics

syndromic intellectual disabilityMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0000508

Submitter: ClinGen

*NAA20* encodes the catalytic subunit of N-acetyltransferase complex B (NatB), which catalyzes acetylation of specific N-terminal methionine residues on proteins. *NAA20* was first reported in relation to autosomal recessive syndromic intellectual disability in 2021 (PMID: 34230638). Affected individuals present with global developmental delay, intellectual disability, impaired speech, and microcephaly. Additional features observed in some individuals include facial dysmorphisms, brain malformations (such as corpus callosum dysgenesis, malformations of cortical development, and cerebellar dysplasia), ataxic gait, congenital heart defects, and epilepsy (PMIDs: 34230638, 37191084). To date, the phenotypic spectrum has been described based on a limited number of affected individuals (n=7) from 3 unrelated families (PMIDs: 34230638, 37191084). Therefore, identification and characterization of additional families will be important to further delineate the full clinical spectrum of this condition. Four variants (3 missense, 1 frameshift) that have been reported in 3 probands in 2 publications (PMIDs: 34230638, 37191084) are included in this curation. Variants in this gene segregated with disease in 4 additional family members. Functional studies of the reported missense variants demonstrate impaired acetylation activity and/or disruption of NatB complex formation (PMIDs: 34230638, 37191084). The mechanism of pathogenicity appears to be loss of function (PMIDs: 34230638, 37191084), but additional studies are needed to better understand the pathogenesis of different *NAA20* variants. This gene–disease relationship is further supported by biochemical evidence. Other subunits of the N-alpha-terminal acetyltransferase family have been implicated in neurodevelopmental disorders with overlapping phenotypes, including *NAA10* and *NAA15*. In summary, there is moderate evidence supporting the relationship between *NAA20* and autosomal recessive syndromic intellectual disability. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged. The classification was upgraded from limited to moderate due to phenotypic overlap among affected individuals and functional studies showing reduced NAA20 catalytic activity. This classification was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on April 1, 2026 (SOP Version 12).

intellectual developmental disorder, autosomal recessive 73LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0030533

Submitter: G2P

intellectual developmental disorder, autosomal recessive 73STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030533

Submitter: PanelApp Australia

intellectual developmental disorder, autosomal recessive 73STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030533

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Intellectual developmental disorder, autosomal recessive 73AR

Manifestation: Cardiovascular; Craniofacial; Musculoskeletal; Neurologic

Intervention: Cardiovascular

Rationale: Among other findings, the condition can include congenital cardiac anomalies, and awareness may allow early intervention and management

Refs: 34230638

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NAA20 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 15

Intellectual developmental disorder, autosomal recessive 73Total: 8

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016100.5. 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		5
missense	1 clinvar	1 clinvar	19 clinvar			21
nonsense	1 clinvar		1 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	2	1	22	3	0	28

Highest pathogenic variant AF is 0.0000013704393

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016100.5	RefSeq	NP_057184.1	6	MANE Select
ENST00000334982.9	Ensembl	ENSP00000335636.4	6	MANE Select
NM_181527.3	RefSeq	NP_852668.1	6	Standard
NM_181528.3	RefSeq	NP_852669.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Metapathway biotransformation Phase I and II

Biological Process

N-terminal peptidyl-methionine acetylation

Molecular Function

peptide alpha-N-acetyltransferase activity

Cellular Component

nucleus
cytoplasm
cytosol
NatB complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000334982
Coding exons: 6
Length: 16540
Individuals with no LoFs: 125717
Homozygous LoFs: 0
Heterozygous LoFs: 31
Defined: 125748
p: 0.000123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.31	65	102	0.635	0.00000523	1160
Missense (PolyPhen)		10	24.966	0.40055		287
Synonymous	-0.552	42	37.7	1.11	0.00000225	334
Loss of Function	1.52	5	10.2	0.488	4.97e-7	129

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00032	0.00031	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.00069	0.00069	rare
European (Non-Finnish)	0.000080	0.000079	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalytic subunit of the NatB complex which catalyzes acetylation of the N-terminal methionine residues of peptides beginning with Met-Asp, Met-Glu, Met-Asn and Met-Gln. Proteins with cell cycle functions are overrepresented in the pool of NatB substrates. Required for maintaining the structure and function of actomyosin fibers and for proper cellular migration. {ECO:0000269|PubMed:18570629}.;

Recessive Scores

pRec: 0.0948

Intolerance Scores

LoFtool: 0.798
RVIS EVS: -0.16
RVIS percentile EVS: 41.25

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.730

Gene Damage Prediction

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