COMTD1

Summary

COMTD1 (catechol-O-methyltransferase domain containing 1, HGNC:26309) is a protein-coding gene on chromosome 10q22.2, encoding Catechol O-methyltransferase domain-containing protein 1 (Q86VU5). Putative O-methyltransferase.

Predicted to enable S-adenosylmethionine-dependent methyltransferase activity. Predicted to be involved in methylation. Located in mitochondrion.

Source: NCBI Gene 118881 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 61 total
• MANE Select transcript: NM_144589

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26309
Approved symbol	COMTD1
Name	catechol-O-methyltransferase domain containing 1
Location	10q22.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ23841
Ensembl gene	ENSG00000165644
Ensembl biotype	protein_coding
OMIM	621350
Entrez	118881

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 protein_coding, 5 protein_coding_CDS_not_defined

ENST00000372538, ENST00000460899, ENST00000469299, ENST00000470947, ENST00000490521, ENST00000491270, ENST00000494596, ENST00000866708, ENST00000866709, ENST00000866710, ENST00000866711, ENST00000866712

RefSeq mRNA: 1 — MANE Select: NM_144589 NM_144589

CCDS: CCDS7349

Canonical transcript exons

ENST00000372538 — 7 exons

Exon	Start	End
ENSE00001094999	75235616	75235743
ENSE00001458062	75235835	75235957
ENSE00001928983	75233641	75234225
ENSE00003366406	75235267	75235372
ENSE00003498467	75235060	75235178
ENSE00003653370	75234610	75234743
ENSE00003684210	75234938	75234992

Expression profiles

Bgee: expression breadth ubiquitous, 213 present calls, max score 97.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.3520 / max 145.9400, expressed in 1730 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
110141	9.1263	1689
110140	0.5451	300
110142	0.5091	272
110139	0.1715	77

Top tissues by expression

239 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	97.99	gold quality
mucosa of transverse colon	UBERON:0004991	97.83	gold quality
body of pancreas	UBERON:0001150	97.68	gold quality
apex of heart	UBERON:0002098	96.36	gold quality
esophagus mucosa	UBERON:0002469	96.13	gold quality
metanephros cortex	UBERON:0010533	93.41	gold quality
heart left ventricle	UBERON:0002084	92.12	gold quality
cardiac ventricle	UBERON:0002082	91.72	gold quality
esophagus	UBERON:0001043	91.52	gold quality
kidney epithelium	UBERON:0004819	91.32	gold quality
transverse colon	UBERON:0001157	91.23	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.18	gold quality
ileal mucosa	UBERON:0000331	91.02	gold quality
right lobe of liver	UBERON:0001114	90.97	gold quality
body of stomach	UBERON:0001161	90.96	gold quality
minor salivary gland	UBERON:0001830	90.02	gold quality
adenohypophysis	UBERON:0002196	89.96	gold quality
small intestine	UBERON:0002108	89.92	gold quality
right lobe of thyroid gland	UBERON:0001119	89.89	gold quality
pancreatic ductal cell	CL:0002079	89.83	silver quality
cortical plate	UBERON:0005343	89.79	gold quality
duodenum	UBERON:0002114	89.78	gold quality
skin of abdomen	UBERON:0001416	89.56	gold quality
vagina	UBERON:0000996	89.54	gold quality
granulocyte	CL:0000094	89.46	gold quality
mouth mucosa	UBERON:0003729	89.31	gold quality
left lobe of thyroid gland	UBERON:0001120	89.30	gold quality
pituitary gland	UBERON:0000007	89.29	gold quality
right atrium auricular region	UBERON:0006631	89.08	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.89	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

4 targeting COMTD1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-4758-3P	99.12	63.96	869
HSA-MIR-4286	97.20	64.37	1587

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	comtd1	ENSDARG00000078918
mus_musculus	Comtd1	ENSMUSG00000021773
rattus_norvegicus	Comtd1	ENSRNOG00000013968
caenorhabditis_elegans		WBGENE00012518
caenorhabditis_elegans		WBGENE00021487
caenorhabditis_elegans		WBGENE00021491
caenorhabditis_elegans		WBGENE00021492

Paralogs (2): COMT (ENSG00000093010), TOMT (ENSG00000284844)

Protein

Protein identifiers

Catechol O-methyltransferase domain-containing protein 1 — Q86VU5 (reviewed: Q86VU5)

All UniProt accessions (2): Q86VU5, R4GNF4

UniProt curated annotations — full annotation on UniProt →

Function. Putative O-methyltransferase.

Subunit / interactions. Homodimer.

Subcellular location. Membrane.

Similarity. Belongs to the class I-like SAM-binding methyltransferase superfamily. Cation-dependent O-methyltransferase family.

RefSeq proteins (1): NP_653190* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002935	SAM_O-MeTrfase	Family
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily
IPR050362	Cation-dep_OMT	Family

Pfam: PF01596

UniProt features (30 total): helix 10, binding site 9, strand 7, chain 1, transmembrane region 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2AVD	X-RAY DIFFRACTION	1.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86VU5-F1	89.67	0.84

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (9): 194; 108; 110–111; 116; 134; 135; 163; 185; 187

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 122 (showing top): TGACCTY_ERR1_Q2, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM2, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, GOBP_METHYLATION, TGACCTTG_SF1_Q6, GOMF_O_METHYLTRANSFERASE_ACTIVITY, GOMF_S_ADENOSYLMETHIONINE_DEPENDENT_METHYLTRANSFERASE_ACTIVITY, GOMF_TRANSFERASE_ACTIVITY_TRANSFERRING_ONE_CARBON_GROUPS, CHEN_METABOLIC_SYNDROM_NETWORK, MARTENS_TRETINOIN_RESPONSE_DN, LU_EZH2_TARGETS_UP, AKT_UP.V1_UP, MTOR_UP.V1_UP, CBX5_TARGET_GENES, CEBPZ_TARGET_GENES

GO Biological Process (1): methylation (GO:0032259)

GO Molecular Function (5): O-methyltransferase activity (GO:0008171), S-adenosylmethionine-dependent methyltransferase activity (GO:0008757), protein binding (GO:0005515), methyltransferase activity (GO:0008168), transferase activity (GO:0016740)

GO Cellular Component (2): mitochondrion (GO:0005739), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
methyltransferase activity	2
metabolic process	1
binding	1
transferase activity, transferring one-carbon groups	1
catalytic activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1622 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COMTD1	DUS2	Q9NX74	530
COMTD1	DNAJC1	Q96KC8	510
COMTD1	MAP6D1	Q9H9H5	500
COMTD1	PAXBP1	Q9Y5B6	489
COMTD1	DISP2	A7MBM2	478
COMTD1	TMC4	Q7Z404	460
COMTD1	COPRS	Q9NQ92	459
COMTD1	PODXL2	Q9NZ53	451
COMTD1	HTR1E	P28566	450
COMTD1	CAMK1G	Q96NX5	438
COMTD1	MDN1	Q9NU22	428
COMTD1	MCRIP2	Q9BUT9	415
COMTD1	ZNF503	Q96F45	415
COMTD1	ZNF23	P17027	409
COMTD1	TOMM5	Q8N4H5	400

IntAct

37 interactions, top by confidence:

A	B	Type	Score
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
UBQLN1	COMTD1	psi-mi:“MI:0915”(physical association)	0.560
KPNB1	POM121C	psi-mi:“MI:0914”(association)	0.530
COMTD1	IFRD1	psi-mi:“MI:0914”(association)	0.530
PBXIP1	GOLIM4	psi-mi:“MI:0914”(association)	0.530
PEX19	MYO1D	psi-mi:“MI:0914”(association)	0.530
ANKH	FAM234B	psi-mi:“MI:0914”(association)	0.530
MAD2L2		psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
PNO1	MTMR3	psi-mi:“MI:0914”(association)	0.350
COQ9	NDUFS8	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
CNR2	ILVBL	psi-mi:“MI:0914”(association)	0.350
COMTD1	TARS3	psi-mi:“MI:0914”(association)	0.350
UPK2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
PEX19	KCNN4	psi-mi:“MI:0914”(association)	0.350
COMTD1	TNPO2	psi-mi:“MI:0914”(association)	0.350
FECH	GTPBP10	psi-mi:“MI:0914”(association)	0.350
COMTD1	TRIO	psi-mi:“MI:0914”(association)	0.350
GPM6A	SERPINA1	psi-mi:“MI:0914”(association)	0.350
SLC22A14	CLGN	psi-mi:“MI:0914”(association)	0.350
SLC28A3	CLGN	psi-mi:“MI:0914”(association)	0.350
SLC30A5	NBAS	psi-mi:“MI:0914”(association)	0.350
SLC39A11	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC39A13	SCO1	psi-mi:“MI:0914”(association)	0.350

BioGRID (310): COMTD1 (Two-hybrid), COMTD1 (Affinity Capture-MS), MSTO1 (Affinity Capture-MS), PHKA1 (Affinity Capture-MS), EPRS (Affinity Capture-MS), EIF4G3 (Affinity Capture-MS), DDX20 (Affinity Capture-MS), RARS (Affinity Capture-MS), DARS (Affinity Capture-MS), SETX (Affinity Capture-MS), TFIP11 (Affinity Capture-MS), BZW1 (Affinity Capture-MS), IPO7 (Affinity Capture-MS), HEATR3 (Affinity Capture-MS), TNPO2 (Affinity Capture-MS)

ESM2 similar proteins: A1A4L8, A1A4Q9, A1L134, A2BDX3, A5YM72, A6H707, B0BLZ5, B0JZP3, G3MZR2, O43292, O60831, O89109, P70295, Q11130, Q2TBP5, Q2V8X7, Q32NY4, Q3UPE3, Q4R4E4, Q4R4I9, Q5XIE1, Q5ZIW1, Q66HR0, Q6IQX7, Q6NRK8, Q6P2H8, Q7L1V2, Q80ZW2, Q86VU5, Q8IZ52, Q8N3Y3, Q8NE01, Q8NF37, Q8NI29, Q8TAC2, Q8TCD5, Q8TD43, Q8WUY1, Q92839, Q96DE0

Diamond homologs: A0A077ES70, A0A077ESS0, A0A077EW86, A0A077EWA5, A0A077EYL8, A0A0S2UWA5, A0A0S2UWC9, A0A0S2UWT1, A0A2H5AIZ6, C7AE94, O04854, O04899, O24144, O24149, O24150, O24151, O49499, O65162, O65862, O65922, O81185, P28034, P93711, Q00719, Q40313, Q41720, Q42945, Q43095, Q43161, Q43237, Q55AS5, Q7F8T6, Q86IC8, Q86IC9, Q86VU5, Q8BIG7, Q8H9B6, Q9C5D7, Q9C9W3, Q9C9W4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 47 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
zinc ion transmembrane transport	6	102.8×	3e-09
intracellular zinc ion homeostasis	5	58.7×	2e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

61 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	48
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

528 predictions. Top by Δscore:

Variant	Effect	Δscore
10:75234604:CCTT:C	donor_loss	1.0000
10:75234605:CTTA:C	donor_loss	1.0000
10:75234606:TTACT:T	donor_loss	1.0000
10:75234607:TACTC:T	donor_loss	1.0000
10:75234608:A:AC	donor_gain	1.0000
10:75234608:A:T	donor_loss	1.0000
10:75234608:ACT:A	donor_gain	1.0000
10:75234609:C:CA	donor_gain	1.0000
10:75234609:CT:C	donor_gain	1.0000
10:75234609:CTC:C	donor_gain	1.0000
10:75234631:T:TA	donor_gain	1.0000
10:75234739:CTCGT:C	acceptor_gain	1.0000
10:75234741:CGT:C	acceptor_gain	1.0000
10:75234741:CGTCT:C	acceptor_gain	1.0000
10:75234742:GT:G	acceptor_gain	1.0000
10:75234743:TCTT:T	acceptor_loss	1.0000
10:75234744:C:CA	acceptor_loss	1.0000
10:75234744:C:CC	acceptor_gain	1.0000
10:75234745:T:A	acceptor_loss	1.0000
10:75234745:T:C	acceptor_gain	1.0000
10:75234745:T:TC	acceptor_gain	1.0000
10:75234748:C:CT	acceptor_gain	1.0000
10:75234749:G:T	acceptor_gain	1.0000
10:75235282:T:TA	donor_gain	1.0000
10:75235606:C:CA	donor_gain	1.0000
10:75235830:CTCA:C	donor_loss	1.0000
10:75235831:TCA:T	donor_loss	1.0000
10:75235832:CAC:C	donor_loss	1.0000
10:75235833:A:AC	donor_gain	1.0000
10:75235833:AC:A	donor_gain	1.0000

AlphaMissense

1631 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:75234118:G:C	S248R	0.989
10:75234118:G:T	S248R	0.989
10:75234120:T:G	S248R	0.989
10:75234709:G:C	F179L	0.976
10:75234709:G:T	F179L	0.976
10:75234711:A:G	F179L	0.976
10:75234701:G:T	A182D	0.963
10:75234654:A:G	C198R	0.954
10:75234137:T:A	D242V	0.950
10:75235166:C:A	G114V	0.948
10:75234089:A:G	L258S	0.946
10:75235171:G:C	F112L	0.945
10:75235171:G:T	F112L	0.945
10:75235173:A:G	F112L	0.945
10:75234620:G:T	A209D	0.942
10:75234146:A:G	I239T	0.941
10:75234079:C:A	K261N	0.935
10:75234079:C:G	K261N	0.935
10:75234086:G:T	A259D	0.933
10:75235068:A:G	W147R	0.932
10:75235068:A:T	W147R	0.932
10:75235307:G:C	N96K	0.932
10:75235307:G:T	N96K	0.932
10:75234138:C:G	D242H	0.931
10:75234652:G:C	C198W	0.929
10:75235166:C:T	G114D	0.928
10:75234095:A:G	L256P	0.926
10:75235305:A:G	L97P	0.925
10:75234082:G:C	F260L	0.924
10:75234082:G:T	F260L	0.924

dbSNP variants (sampled 300 via entrez): RS1000256908 (10:75234371 G>A), RS1000309484 (10:75234624 G>A), RS1000546971 (10:75235525 G>A), RS1000653219 (10:75235993 C>G,T), RS1001442998 (10:75235087 C>CG), RS1001687623 (10:75237385 G>A), RS1001735215 (10:75237698 G>A), RS1003699334 (10:75234463 G>A), RS1004393127 (10:75233835 G>A), RS1004708808 (10:75233254 C>T), RS1004777679 (10:75235358 C>G), RS1005161714 (10:75233549 T>G), RS1005490810 (10:75237781 G>A,C), RS1006492000 (10:75236169 A>G), RS1006544414 (10:75236442 C>T)

Disease associations

OMIM: gene MIM:621350 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001585_34	Breast size	6.000000e-06
GCST006483_5	Lung function (FVC)	5.000000e-08
GCST006483_6	Lung function (FVC)	3.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004312	vital capacity

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

37 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects cotreatment, increases expression, affects expression	8
sodium arsenite	decreases expression, increases expression	2
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
sodium arsenate	decreases expression, increases abundance	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Temozolomide	increases expression	1
Acetaminophen	decreases expression	1
Arsenic	decreases expression, increases abundance	1
Catechin	affects cotreatment, decreases expression	1
Cisplatin	increases expression, affects cotreatment	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Demecolcine	decreases expression	1
Doxorubicin	increases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SJ51	HAP1 COMTD1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.