PNMT

protein-coding

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

Gene summary

The product of this gene catalyzes the last step of the catecholamine biosynthesis pathway, which methylates norepinephrine to form epinephrine (adrenaline). The enzyme also has beta-carboline 2N-methyltransferase activity. This gene is thought to play a key step in regulating epinephrine production. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Nov 2012]

Previous symbols:

PENT

MANE transcript

NM_002686.4

Inheritance

—

ClinVar variants

U:52B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.51

Max pathogenic AF

—

Genomic locus

chr17:39,667,981-39,670,475

External References & Databases

Ensembl (ENSG00000141744)

Transcript & Mutation Effects

hg38 • Region Span ~2.5 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 PNMT variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 53

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002686.4. 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					1 clinvar	1
missense			52 clinvar	3 clinvar	1 clinvar	56
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	52	3	2	57

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002686.4	RefSeq	NP_002677.1	3	MANE Select
ENST00000269582.3	Ensembl	ENSP00000269582.2	3	MANE Select
ENST00000394246.1	Ensembl	ENSP00000377791.1	2	Standard
ENST00000394246.2	Ensembl	ENSP00000377791.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Tyrosine metabolism - Homo sapiens (human)
Tyrosine hydroxylase deficiency
Tyrosinemia, transient, of the newborn
Dopamine beta-hydroxylase deficiency
Disulfiram Action Pathway

Biological Process

methylation
epinephrine biosynthetic process
catecholamine biosynthetic process

Molecular Function

phenylethanolamine N-methyltransferase activity

Cellular Component

cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000269582
Coding exons: 3
Length: 2495
Individuals with no LoFs: 125679
Homozygous LoFs: 0
Heterozygous LoFs: 56
Defined: 125735
p: 0.000223

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.449	157	174	0.904	0.0000102	1777
Missense (PolyPhen)		63	74.172	0.84938		810
Synonymous	0.626	67	73.8	0.907	0.00000428	591
Loss of Function	1.41	5	9.73	0.514	5.01e-7	96

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00038	0.00037	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000061	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00037	0.00036	rare
South Asian	0.00016	0.00016	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Converts noradrenaline to adrenaline.;

Recessive Scores

pRec: 0.333

Intolerance Scores

LoFtool: 0.674
RVIS EVS: 0.06
RVIS percentile EVS: 58.74

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.958

Gene Damage Prediction

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