COMTD1

protein-coding

catechol-O-methyltransferase domain containing 1, the group of 7BS small molecule methyltransferases

Gene summary

Predicted to enable S-adenosylmethionine-dependent methyltransferase activity. Predicted to be involved in methylation. Located in mitochondrion. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_144589.4

Inheritance

—

ClinVar variants

U:46B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.75

Max pathogenic AF

—

Genomic locus

chr10:75,233,641-75,236,030

External References & Databases

Ensembl (ENSG00000165644)

Transcript & Mutation Effects

hg38 • Region Span ~2.4 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 COMTD1 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 44

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_144589.4. 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						0
missense			45 clinvar	1 clinvar		46
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	46	1	0	47

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 24 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_144589.4	RefSeq	NP_653190.2	7	MANE Select
ENST00000372538.8	Ensembl	ENSP00000361616.3	7	MANE Select
ENST00000469299.1	Ensembl	ENSP00000473626.1	7	Standard
ENST00000866708.1	Ensembl	ENSP00000536767.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

methylation

Molecular Function

protein binding
O-methyltransferase activity
S-adenosylmethionine-dependent methyltransferase activity

Cellular Component

integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000372538
Coding exons: 7
Length: 2062
Individuals with no LoFs: 125533
Homozygous LoFs: 0
Heterozygous LoFs: 57
Defined: 125590
p: 0.000227

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.922	87	115	0.758	0.00000523	1569
Missense (PolyPhen)		24	35.431	0.67737		515
Synonymous	1.55	40	54.5	0.734	0.00000258	570
Loss of Function	0.750	8	10.6	0.752	4.97e-7	133

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0018	0.0013	notable
Latino/Admixed American	0.00031	0.00029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00038	0.00038	rare
Finnish	0.00016	0.00014	rare
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.00011	0.000098	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Putative O-methyltransferase. {ECO:0000305}.;

Recessive Scores

pRec: 0.171

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.589

Gene Damage Prediction

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