INMT

protein-coding

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

Gene summary

N-methylation of endogenous and xenobiotic compounds is a major method by which they are degraded. This gene encodes an enzyme that N-methylates indoles such as tryptamine. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the downstream MINDY4 (aka FAM188B) gene. In rodents and other mammals such as cetartiodactyla this gene is in the opposite orientation compared to its orientation in human and other primates and this gene appears to have been lost in carnivora and chiroptera. [provided by RefSeq, Jul 2019]

MANE transcript

NM_006774.5

Inheritance

—

ClinVar variants

U:50B:10

Top phenotype

Prostate cancer

gnomAD constraint

pLI —, LoF o/e 0.77

Max pathogenic AF

—

Genomic locus

chr7:30,697,985-30,757,602

External References & Databases

Ensembl (ENSG00000241644)

Transcript & Mutation Effects

hg38 • Region Span ~59.6 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 INMT variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 54

not providedTotal: 7

Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006774.5. 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	4 clinvar	5
missense			50 clinvar	3 clinvar	1 clinvar	54
nonsense					1 clinvar	1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	50	4	6	60

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006774.5	RefSeq	NP_006765.4	3	MANE Select
ENST00000013222.5	Ensembl	ENSP00000013222.5	3	MANE Select
NM_001199219.2	RefSeq	NP_001186148.1	3	Standard
ENST00000409539.1	Ensembl	ENSP00000386961.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Tryptophan metabolism - Homo sapiens (human)
Selenocompound metabolism - Homo sapiens (human)
Tryptophan Metabolism
Tryptophan metabolism
Methylation Pathways

Biological Process

amine metabolic process
response to toxic substance
methylation

Molecular Function

thioether S-methyltransferase activity
protein binding
amine N-methyltransferase activity
S-adenosyl-L-methionine:beta-alanine N-methyltransferase activity

Cellular Component

cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000013222
Coding exons: 3
Length: 59618
Individuals with no LoFs: 125698
Homozygous LoFs: 0
Heterozygous LoFs: 50
Defined: 125748
p: 0.000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.358	168	155	1.08	0.00000963	1687
Missense (PolyPhen)		52	48.941	1.0625		599
Synonymous	-0.922	78	68.3	1.14	0.00000441	541
Loss of Function	0.481	4	5.18	0.772	2.19e-7	67

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0015	0.0015	notable
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000079	0.000079	rare
South Asian	0.00026	0.00026	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Functions as thioether S-methyltransferase and is active with a variety of thioethers and the corresponding selenium and tellurium compounds, including 3-methylthiopropionaldehyde, dimethyl selenide, dimethyl telluride, 2-methylthioethylamine, 2- methylthioethanol, methyl-n-propyl sulfide and diethyl sulfide. Plays an important role in the detoxification of selenium compounds (By similarity). Catalyzes the N-methylation of tryptamine and structurally related compounds. {ECO:0000250, ECO:0000269|PubMed:10552930}.;

Recessive Scores

pRec: 0.111

Intolerance Scores

LoFtool: 0.765
RVIS EVS: 1.98
RVIS percentile EVS: 97.61

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.912

Gene Damage Prediction

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