NAA80

protein-coding

N-alpha-acetyltransferase 80, NatH catalytic subunit, the group of GCN5 related N-acetyltransferases|N-alpha-acetyltransferase subunits

Gene summary

This gene encodes a member of the N-acetyltransferase family. N-acetyltransferases modify proteins by transferring acetyl groups from acetyl CoA to the N-termini of protein substrates. The encoded protein is a cytoplasmic N-acetyltransferase with a substrate specificity for proteins with an N-terminal methionine. This gene is located in the tumor suppressor gene region on chromosome 3p21.3 and the encoded protein may play a role in cancer. Alternatively spliced transcript variants encoding multiple isoforms have been observed. This gene overlaps and is on the same strand as hyaluronoglucosaminidase 3, and some transcripts of each gene share a portion of the first exon. [provided by RefSeq, Jan 2011]

Previous symbols:

NAT6

MANE transcript

NM_001200016.2

Inheritance

ClinVar variants

P:1U:56B:8

Top phenotype

Auroneurodental syndrome

gnomAD constraint

pLI —, LoF o/e 0.32

Max pathogenic AF

—

Genomic locus

chr3:50,296,402-50,299,416

External References & Databases

Ensembl (ENSG00000243477)

Transcript & Mutation Effects

hg38 • Region Span ~3.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

auroneurodental syndromeLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0970998

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Auroneurodental syndromeAR

Manifestation: Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Dental; Neurologic

Intervention: Audiologic/Otolaryngologic

Rationale: Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development

Refs: 34805998

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NAA80 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 62

not providedTotal: 2

Auroneurodental syndromeTotal: 1

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001200016.2. 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					1 clinvar	1
missense		1 clinvar	56 clinvar	7 clinvar		64
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	1	56	7	1	65

Highest pathogenic variant AF is 6.9611025e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 21 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001200016.2	RefSeq	NP_001186945.1	1	MANE Select
ENST00000443094.3	Ensembl	ENSP00000410610.2	1	MANE Select
NM_001200018.2	RefSeq	NP_001186947.1	1	Standard
NM_012191.4	RefSeq	NP_036323.2	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein acetylation
regulation of actin polymerization or depolymerization
N-terminal peptidyl-aspartic acid acetylation
N-terminal peptidyl-glutamic acid acetylation
actin modification

Molecular Function

peptide alpha-N-acetyltransferase activity
N-acetyltransferase activity
acetyl-CoA binding

Cellular Component

cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000354862
Coding exons: 2
Length: 3020
Individuals with no LoFs: 124795
Homozygous LoFs: 0
Heterozygous LoFs: 18
Defined: 124813
p: 0.0000721

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.563	155	176	0.880	0.0000103	1924
Missense (PolyPhen)		52	66.061	0.78715		744
Synonymous	0.719	64	71.7	0.892	0.00000339	733
Loss of Function	1.58	2	6.29	0.318	3.51e-7	74

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00013	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00010	0.000097	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: N-alpha-acetyltransferase that specifically mediates the acetylation of the acidic amino terminus of processed forms of beta- and gamma-actin (ACTB and ACTG, respectively) (PubMed:30028079, PubMed:29581253). N-terminal acetylation of processed beta- and gamma-actin regulates actin filament depolymerization and elongation (PubMed:29581253). In vivo, preferentially displays N-terminal acetyltransferase activity towards acid N-terminal sequences starting with Asp-Asp-Asp and Glu-Glu-Glu (PubMed:30028079, PubMed:29581253). In vitro, shows high activity towards Met-Asp-Glu-Leu and Met-Asp-Asp-Asp (PubMed:10644992, PubMed:29581307). May act as a tumor suppressor (PubMed:10644992). {ECO:0000269|PubMed:10644992, ECO:0000269|PubMed:29581253, ECO:0000269|PubMed:29581307, ECO:0000269|PubMed:30028079}.;

Recessive Scores

pRec: 0.0776

Intolerance Scores

RVIS EVS: 0.35
RVIS percentile EVS: 74.49

Essentials

Essential (gene trap): N