NNMT

protein-coding

nicotinamide N-methyltransferase, the group of 7BS small molecule methyltransferases

Gene summary

N-methylation is one method by which drug and other xenobiotic compounds are metabolized by the liver. This gene encodes the protein responsible for this enzymatic activity which uses S-adenosyl methionine as the methyl donor. [provided by RefSeq, Jul 2008]

MANE transcript

NM_006169.3

Inheritance

—

ClinVar variants

U:50B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.25

Max pathogenic AF

—

Genomic locus

chr11:114,257,787-114,313,536

External References & Databases

Ensembl (ENSG00000166741)

Transcript & Mutation Effects

hg38 • Region Span ~55.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NNMT variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 48

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006169.3. 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			2 clinvar			2
missense			48 clinvar	1 clinvar		49
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	50	1	0	51

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 44 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006169.3	RefSeq	NP_006160.1	3	MANE Select
ENST00000299964.4	Ensembl	ENSP00000299964.3	3	MANE Select
NM_001372045.1	RefSeq	NP_001358974.1	3	Standard
NM_001372046.1	RefSeq	NP_001358975.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Nicotinate and nicotinamide metabolism - Homo sapiens (human)
Nicotinate and Nicotinamide Metabolism
Metapathway biotransformation Phase I and II
Methylation Pathways
Methylation

Biological Process

response to organonitrogen compound
animal organ regeneration
methylation
NAD biosynthesis via nicotinamide riboside salvage pathway
response to drug

Molecular Function

nicotinamide N-methyltransferase activity
pyridine N-methyltransferase activity

Cellular Component

cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000535401
Coding exons: 3
Length: 55499
Individuals with no LoFs: 125694
Homozygous LoFs: 0
Heterozygous LoFs: 53
Defined: 125747
p: 0.000211

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.19	188	147	1.28	0.00000801	1721
Missense (PolyPhen)		65	43.97	1.4783		598
Synonymous	-0.682	73	66.0	1.11	0.00000407	534
Loss of Function	-0.665	10	7.97	1.25	3.35e-7	108

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.00035	0.00035	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.000055	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00026	0.00025	rare
South Asian	0.000065	0.000065	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalyzes the N-methylation of nicotinamide and other pyridines to form pyridinium ions. This activity is important for biotransformation of many drugs and xenobiotic compounds.;

Recessive Scores

pRec: 0.202

Intolerance Scores

LoFtool: 0.620
RVIS EVS: -0.47
RVIS percentile EVS: 23.25

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.981

Gene Damage Prediction

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