N6AMT1

N-6 adenine-specific DNA methyltransferase 1, the group of 7BS protein methyltransferases

Basic information

Region (hg38): 21:28872190-28885371

Previous symbols: [ "C21orf127", "HEMK2" ]

Links

ENSG00000156239 ∙ NCBI:29104 ∙ OMIM:614553 ∙ HGNC:16021 ∙ Uniprot:Q9Y5N5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the N6AMT1 gene.

• Inborn genetic diseases (17 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the N6AMT1 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						0
missense			16	2		18
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	16	2	0

Variants in N6AMT1

This is a list of pathogenic ClinVar variants found in the N6AMT1 region.

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

Position	Type	Phenotype	Significance	ClinVar
21-28876407-A-G		not specified	Uncertain significance (Apr 12, 2023)
21-28878201-T-C		not specified	Uncertain significance (Jan 06, 2023)
21-28878251-G-A			Likely benign (Jan 01, 2023)
21-28878273-C-T		not specified	Uncertain significance (Jan 04, 2022)
21-28878321-C-T		not specified	Uncertain significance (Jan 30, 2024)
21-28879884-T-G		not specified	Uncertain significance (Oct 18, 2021)
21-28879887-C-G		not specified	Uncertain significance (Aug 10, 2021)
21-28879895-G-C		not specified	Uncertain significance (Dec 28, 2022)
21-28879908-C-T		not specified	Uncertain significance (Apr 12, 2022)
21-28879938-G-A		not specified	Uncertain significance (Sep 16, 2021)
21-28883046-A-C		not specified	Likely benign (Oct 12, 2022)
21-28885219-G-C		not specified	Uncertain significance (Sep 13, 2023)
21-28885233-G-T		not specified	Uncertain significance (Oct 07, 2022)
21-28885257-A-T		not specified	Uncertain significance (Apr 17, 2023)
21-28885269-G-A		not specified	Uncertain significance (Aug 02, 2021)
21-28885272-G-A		not specified	Uncertain significance (Jun 16, 2023)
21-28885293-G-C		not specified	Uncertain significance (Feb 05, 2024)
21-28885309-G-T		not specified	Uncertain significance (Dec 26, 2023)
21-28885324-T-C		not specified	Uncertain significance (Jun 11, 2021)
21-28885327-C-T		not specified	Uncertain significance (May 17, 2023)
21-28885341-G-A		not specified	Uncertain significance (Jun 21, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
N6AMT1	protein_coding	protein_coding	ENST00000303775	6	13181

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000682	0.293	124720	0	1007	125727	0.00401

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.230	123	116	1.06	0.00000549	1349
Missense in Polyphen		28	36.289	0.77158		422
Synonymous	0.0938	43	43.8	0.982	0.00000219	440
Loss of Function	0.0962	8	8.30	0.964	3.47e-7	112

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00705	0.00661
Ashkenazi Jewish	0.000931	0.000893
East Asian	0.00447	0.00370
Finnish	0.0167	0.0162
European (Non-Finnish)	0.00368	0.00343
Middle Eastern	0.00447	0.00370
South Asian	0.000445	0.000425
Other	0.00287	0.00261

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Methyltransferase that can methylate both proteins and DNA, and to a lower extent, arsenic (PubMed:18539146, PubMed:21193388, PubMed:30017583). Catalytic subunit of a heterodimer with TRMT112, which catalyzes N5-methylation of Glu residue of proteins with a Gly-Gln-Xaa-Xaa-Xaa-Arg motif (PubMed:18539146) (By similarity). Methylates ETF1 on 'Gln-185'; ETF1 needs to be complexed to ERF3 in its GTP-bound form to be efficiently methylated (PubMed:18539146, PubMed:20606008). Also acts as a N(6)-adenine-specific DNA methyltransferase by mediating methylation of DNA on the 6th position of adenine (N(6)- methyladenosine) (PubMed:30017583). N(6)-methyladenosine (m6A) DNA is significantly enriched in exonic regions and is associated with gene transcriptional activation (PubMed:30017583). May also play a role in the modulation of arsenic-induced toxicity by mediating the conversion of monomethylarsonous acid (3+) into the less toxic dimethylarsonic acid (PubMed:21193388, PubMed:25997655). It however only plays a limited role in arsenic metabolism compared with AS3MT (PubMed:25997655). {ECO:0000250|UniProtKB:Q6SKR2, ECO:0000269|PubMed:18539146, ECO:0000269|PubMed:20606008, ECO:0000269|PubMed:21193388, ECO:0000269|PubMed:25997655, ECO:0000269|PubMed:30017583}.
• Pathway: Methylation;Phase II - Conjugation of compounds;Eukaryotic Translation Termination;Translation;Metabolism of proteins;Biological oxidations;Metabolism (Consensus)

Recessive Scores

• pRec: 0.0959

Intolerance Scores

• rvis_EVS: 0.73
• rvis_percentile_EVS: 86.08

Haploinsufficiency Scores

• pHI: 0.490
• hipred: N
• hipred_score: 0.292
• ghis: 0.420

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.464

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: N6amt1
• Phenotype: growth/size/body region phenotype; embryo phenotype; 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)

Gene ontology

• Biological process: toxin metabolic process;peptidyl-glutamine methylation;arsonoacetate metabolic process;positive regulation of cell growth;methylation;DNA methylation on adenine
• Cellular component: nucleus;cytosol;protein-containing complex;eRF1 methyltransferase complex
• Molecular function: nucleic acid binding;protein binding;protein methyltransferase activity;S-adenosylmethionine-dependent methyltransferase activity;site-specific DNA-methyltransferase (adenine-specific) activity;methylarsonite methyltransferase activity;protein-glutamine N-methyltransferase activity