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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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NAA38
N-alpha-acetyltransferase 38, NatC auxiliary subunit
Chromosome 17 · 17p13.1
NCBI Gene: 84316Ensembl: ENSG00000183011.14HGNC: HGNC:28212UniProt: I3L3Z2
15PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
NatC complexprotein bindingnegative regulation of apoptotic processnucleushypertensiongoutmusculoskeletal system diseasegenetic disorder
✦AI Summary

NAA38 is an auxiliary subunit of the N-terminal acetyltransferase C (NatC) complex, which catalyzes acetylation of N-terminal methionine residues on approximately 80% of human proteins 1. NAA38 functions alongside the catalytic subunit NAA30 and the large auxiliary subunit NAA35 to facilitate N-terminal acetylation, primarily through co-translational mechanisms at the ribosome 2. Structurally, NAA38 increases NatC thermostability and broadens substrate specificity by ordering an NAA35 segment and reorienting NAA30's peptide-binding loop for optimal catalysis 1. N-terminal acetylation mediated by the NatC complex protects proteins from ubiquitin-dependent degradation via the N-end rule pathway, thereby regulating protein stability and cellular function. NAA38 dysfunction has been implicated in multiple disease contexts. Genetic variation in NAA38 was identified as a novel type 1 diabetes susceptibility locus through immune cell transcriptomic analysis 3. NAA38 disruption affects ferroptosis sensitivity by regulating intracellular glutathione levels through NRF2-mediated transcription 4. Additionally, inhibition of the NatC complex (including NAA38) mitigates endoplasmic reticulum stress-induced muscle atrophy in cancer cachexia models 5. A chr17 deletion encompassing NAA38 was associated with congenital hearing loss and speech development delay 6, suggesting NAA38 relevance to neurodevelopmental and sensory function.

Sources cited
1
NAA38 increases thermostability and broadens substrate specificity of NatC by ordering NAA35 and reorienting NAA30's peptide-binding loop
PMID: 36638802
2
NatC complex (NAA30-NAA35-NAA38) acetylates ~20% of proteome co-translationally and is functionally conserved from yeast to human
PMID: 33600573
3
NAA38 identified as novel type 1 diabetes susceptibility gene through immune cell transcriptomic Mendelian randomization
PMID: 41299435
4
NAA38 disruption increases glutathione levels via NRF2 stabilization and affects ferroptosis sensitivity
PMID: 30726737
5
NatC inhibition (including NAA38) prevents ER stress-induced muscle wasting in cancer cachexia via CTSK downregulation
PMID: 41852114
6
NAA38 deletion associated with congenital hearing loss and speech development delay
PMID: 27075776
Disease Associationsⓘ20
hypertensionOpen Targets
0.22Weak
goutOpen Targets
0.22Weak
musculoskeletal system diseaseOpen Targets
0.19Weak
genetic disorderOpen Targets
0.19Weak
Snijders Blok-Campeau syndromeOpen Targets
0.17Weak
clonal hematopoiesisOpen Targets
0.16Weak
Increased blood pressureOpen Targets
0.16Weak
cardiovascular diseaseOpen Targets
0.16Weak
Back painOpen Targets
0.16Weak
COVID-19Open Targets
0.14Weak
essential hypertensionOpen Targets
0.12Weak
thyroid diseaseOpen Targets
0.11Weak
periodontal disorderOpen Targets
0.09Suggestive
tooth diseaseOpen Targets
0.09Suggestive
goiterOpen Targets
0.05Suggestive
ThyrotoxicosisOpen Targets
0.05Suggestive
Meacham syndromeOpen Targets
0.03Suggestive
Hepatic veno-occlusive disease - immunodeficiencyOpen Targets
0.03Suggestive
hepatic veno-occlusive disease-immunodeficiency syndromeOpen Targets
0.03Suggestive
Ascher syndromeOpen Targets
0.02Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
API5Shared pathway100%GMEB1Shared pathway100%SNRPGProtein interaction100%LSM6Protein interaction100%LSM7Protein interaction100%LSM5Protein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
100%
Liver
79%
Lung
69%
Heart
69%
Ovary
55%
Gene Interaction Network
Click a node to explore
NAA38API5GMEB1SNRPGLSM6LSM7LSM5
PROTEIN STRUCTURE
Preparing viewer…
PDB7MX2 · 3.64 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.73LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.16 [0.77–1.73]
RankingsWhere NAA38 stands among ~20K protein-coding genes
  • #15,631of 20,598
    Most Researched15
  • #16,266of 17,882
    Most Constrained (LOEUF)1.73
Genes detectedNAA38
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Molecular role of NAA38 in thermostability and catalytic activity of the human NatC N-terminal acetyltransferase.
PMID: 36638802
Structure · 2023
1.00
2
Immune cell-based transcriptomic Mendelian randomization and colocalization study on type 1 diabetes.
PMID: 41299435
BMC Med · 2025
0.90
3
Human NAA30 can rescue yeast mak3∆ mutant growth phenotypes.
PMID: 33600573
Biosci Rep · 2021
0.80
4
A Genome-wide Haploid Genetic Screen Identifies Regulators of Glutathione Abundance and Ferroptosis Sensitivity.
PMID: 30726737
Cell Rep · 2019
0.70
5
Inhibition of N-Terminal Acetyltransferase C Mitigates Endoplasmic Reticulum Stress-Mediated Muscle Atrophy in Cancer Cachexia.
PMID: 41852114
J Cachexia Sarcopenia Muscle · 2026
0.60