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.

not_specified (58 variants)
not_provided (12 variants)
NAT8L-related_disorder (1 variants)
Microcephaly (1 variants)
N-acetylaspartate_deficiency (1 variants)

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. These statistics are base on transcript: NM_000178557.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	8 clinvar	1 clinvar	10
missense			55 clinvar	3 clinvar		58
nonsense						0
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)						0
Total	0	0	58	11	1

Loading clinvar variants...

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