NAT8L

N-acetyltransferase 8 like, the group of GCN5 related N-acetyltransferases

Basic information

Region (hg38): 4:2059327-2069089

Links

ENSG00000185818 ∙ NCBI:339983 ∙ OMIM:610647 ∙ HGNC:26742 ∙ Uniprot:Q8N9F0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• N-acetylaspartate deficiency (Limited), mode of inheritance: Unknown
• N-acetylaspartate deficiency (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
N-acetylaspartate deficiency	AR	General	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	Biochemical; Neurologic	11310630; 15328569; 16802720; 19807691

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NAT8L gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NAT8L gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				8	2	10
missense			23	2		25
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1	1	2
non coding				1		1
Total	0	0	24	11	2

Variants in NAT8L

This is a list of pathogenic ClinVar variants found in the NAT8L region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-2059524-C-T		not specified	Uncertain significance (Oct 14, 2023)
4-2059527-C-A		not specified	Uncertain significance (Jul 22, 2022)
4-2059554-G-T		not specified	Uncertain significance (Sep 01, 2021)
4-2059564-A-G		not specified	Uncertain significance (Oct 09, 2024)
4-2059576-C-T		not specified	Uncertain significance (May 30, 2024)
4-2059582-C-G		not specified	Uncertain significance (Apr 26, 2024)
4-2059596-G-A		not specified	Uncertain significance (Dec 27, 2023)
4-2059599-G-A		not specified	Uncertain significance (Nov 08, 2024)
4-2059607-C-T		NAT8L-related disorder	Benign (Sep 10, 2019)
4-2059616-C-T			Likely benign (Dec 31, 2019)
4-2059617-G-A		not specified	Uncertain significance (Mar 29, 2023)
4-2059633-C-T		not specified	Uncertain significance (Sep 08, 2024)
4-2059665-C-T		not specified	Uncertain significance (Nov 17, 2023)
4-2059668-C-G		not specified	Uncertain significance (Apr 07, 2023)
4-2059677-C-T		not specified	Uncertain significance (Jul 09, 2024)
4-2059679-A-C			Likely benign (Apr 11, 2018)
4-2059683-G-A		not specified	Uncertain significance (Sep 11, 2024)
4-2059686-C-T		not specified	Uncertain significance (Feb 12, 2024)
4-2059687-C-T		not specified	Uncertain significance (Jun 06, 2023)
4-2059695-C-G		not specified	Uncertain significance (Oct 06, 2021)
4-2059702-A-G		not specified	Uncertain significance (Apr 07, 2023)
4-2059711-CGGGGGGCGCGGGGCCGCCG-C		N-acetylaspartate deficiency	Pathogenic (Dec 14, 2009)
4-2059723-G-C		not specified	Uncertain significance (Jan 04, 2022)
4-2059731-G-C		not specified	Uncertain significance (Oct 12, 2022)
4-2059732-G-T		not specified	Uncertain significance (Dec 05, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NAT8L	protein_coding	protein_coding	ENST00000423729	3	9578

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.865	0.134	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.15	69	141	0.490	0.0000103	1881
Missense in Polyphen		15	54.013	0.27771		447
Synonymous	-0.811	76	67.5	1.13	0.00000513	677
Loss of Function	2.37	0	6.54	0.00	3.65e-7	93

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role in the regulation of lipogenesis by producing N-acetylaspartate acid (NAA), a brain-specific metabolite. NAA occurs in high concentration in brain and its hydrolysis plays a significant part in the maintenance of intact white matter. Promotes dopamine uptake by regulating TNF-alpha expression. Attenuates methamphetamine-induced inhibition of dopamine uptake. {ECO:0000269|PubMed:19524112}.
• Disease: DISEASE: N-acetylaspartate deficiency (NACED) [MIM:614063]: A metabolic disorder resulting in truncal ataxia, marked developmental delay, seizures, and secondary microcephaly. {ECO:0000269|PubMed:19807691}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Alanine, aspartate and glutamate metabolism - Homo sapiens (human);Metapathway biotransformation Phase I and II;Metabolism of amino acids and derivatives;Metabolism;Amino acid synthesis and interconversion (transamination) (Consensus)

Haploinsufficiency Scores

• pHI: 0.222
• hipred: N
• hipred_score: 0.459
• ghis: 0.645

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nat8l
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); homeostasis/metabolism phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: cellular amino acid biosynthetic process
• Cellular component: cytoplasm;mitochondrion;mitochondrial matrix;integral component of membrane;rough endoplasmic reticulum membrane;mitochondrial membrane
• Molecular function: aspartate N-acetyltransferase activity