TMT1B

Summary

TMT1B (thiol methyltransferase 1B, HGNC:28276) is a protein-coding gene on chromosome 12q13.2, encoding Thiol S-methyltransferase TMT1B (Q6UX53). Thiol S-methyltransferase that catalyzes the transfer of a methyl group from S-adenosyl-L-methionine to alkyl and phenolic thiol-containing acceptor substrates.

Enables thiol S-methyltransferase activity. Predicted to be involved in methylation. Predicted to be located in cytosol; endoplasmic reticulum membrane; and lipid droplet.

Source: NCBI Gene 196410 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 52 total
• MANE Select transcript: NM_152637

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28276
Approved symbol	TMT1B
Name	thiol methyltransferase 1B
Location	12q13.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC17301, ALDI
Ensembl gene	ENSG00000170439
Ensembl biotype	protein_coding
Entrez	196410

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000394252

RefSeq mRNA: 1 — MANE Select: NM_152637 NM_152637

CCDS: CCDS8887

Canonical transcript exons

ENST00000394252 — 2 exons

Exon	Start	End
ENSE00001142409	55681736	55682252
ENSE00001907098	55683813	55684611

Expression profiles

Bgee: expression breadth ubiquitous, 171 present calls, max score 98.78.

FANTOM5 (CAGE): breadth broad, TPM avg 5.2630 / max 288.9001, expressed in 793 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
125962	3.6383	672
125961	0.8879	387
125959	0.3671	202
125960	0.3221	181
125963	0.0476	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	98.78	gold quality
mucosa of transverse colon	UBERON:0004991	96.62	gold quality
cardiac muscle of right atrium	UBERON:0003379	96.56	gold quality
right atrium auricular region	UBERON:0006631	96.54	gold quality
cardiac atrium	UBERON:0002081	96.28	gold quality
right lobe of liver	UBERON:0001114	96.24	gold quality
jejunal mucosa	UBERON:0000399	96.09	gold quality
liver	UBERON:0002107	95.41	gold quality
kidney epithelium	UBERON:0004819	93.55	silver quality
corpus epididymis	UBERON:0004359	92.34	gold quality
duodenum	UBERON:0002114	91.30	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.21	gold quality
left ventricle myocardium	UBERON:0006566	89.11	silver quality
colonic mucosa	UBERON:0000317	88.55	gold quality
rectum	UBERON:0001052	88.38	gold quality
myocardium	UBERON:0002349	87.45	gold quality
pancreatic ductal cell	CL:0002079	87.22	silver quality
apex of heart	UBERON:0002098	86.64	gold quality
mucosa of sigmoid colon	UBERON:0004993	86.33	gold quality
heart left ventricle	UBERON:0002084	84.04	gold quality
cardiac ventricle	UBERON:0002082	83.46	gold quality
heart	UBERON:0000948	83.43	gold quality
caput epididymis	UBERON:0004358	83.26	gold quality
gall bladder	UBERON:0002110	83.00	gold quality
small intestine Peyer’s patch	UBERON:0003454	81.94	gold quality
small intestine	UBERON:0002108	81.49	gold quality
adult mammalian kidney	UBERON:0000082	81.05	gold quality
heart right ventricle	UBERON:0002080	80.07	gold quality
transverse colon	UBERON:0001157	79.31	gold quality
kidney	UBERON:0002113	79.30	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.18

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

44 targeting TMT1B, 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-6825-5P	99.96	69.81	3431
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-1909-5P	98.94	64.01	484
HSA-MIR-138-2-3P	98.91	68.33	1643
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-3664-3P	97.85	67.62	1452
HSA-MIR-30C-1-3P	97.80	66.36	1499

Literature-anchored findings (GeneRIF, showing 10)

• Results indicate that METTL7B may promote metastasis of thyroid cancer through EMT and may therefore be considered as a potential biomarker for the diagnosis and prognosis of thyroid carcinoma. (PMID:31121562)
• Low Molecular Pectin Inhibited the Lipid Accumulation by Upregulation of METTL7B. (PMID:33484445)
• Human METTL7B is an alkyl thiol methyltransferase that metabolizes hydrogen sulfide and captopril. (PMID:33649426)
• circ-PSD3 promoted proliferation and invasion of papillary thyroid cancer cells via regulating the miR-7-5p/METTL7B axis. (PMID:33858297)
• Prognostic Potential of METTL7B in Glioma. (PMID:35034026)
• Methyltransferase like 7B is a potential therapeutic target for reversing EGFR-TKIs resistance in lung adenocarcinoma. (PMID:35144642)
• METTL7B contributes to the malignant progression of glioblastoma by inhibiting EGR1 expression. (PMID:35254598)
• Potent necrosis effect of methanethiol mediated by METTL7B enzyme bioactivation mechanism in 16HBE cell. (PMID:35397445)
• Methyltransferase like 7B is upregulated in sepsis and modulates lipopolysaccharide-induced inflammatory response and macrophage polarization. (PMID:35603523)
• The Methyltransferases METTL7A and METTL7B Confer Resistance to Thiol-Based Histone Deacetylase Inhibitors. (PMID:38151817)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tmt1b	ENSMUSG00000025347
rattus_norvegicus	Tmt1b	ENSRNOG00000007927
caenorhabditis_elegans		WBGENE00019675
caenorhabditis_elegans		WBGENE00019961
caenorhabditis_elegans		WBGENE00019963
caenorhabditis_elegans		WBGENE00019968
caenorhabditis_elegans		WBGENE00022781

Paralogs (4): COQ5 (ENSG00000110871), METTL27 (ENSG00000165171), TMT1A (ENSG00000185432), AS3MT (ENSG00000214435)

Protein

Protein identifiers

Thiol S-methyltransferase TMT1B — Q6UX53 (reviewed: Q6UX53)

Alternative names: Methyltransferase-like protein 7B, Thiol S-methyltransferase METTL7B

All UniProt accessions (1): Q6UX53

UniProt curated annotations — full annotation on UniProt →

Function. Thiol S-methyltransferase that catalyzes the transfer of a methyl group from S-adenosyl-L-methionine to alkyl and phenolic thiol-containing acceptor substrates. Together with TMT1B accounts for most of S-thiol methylation activity in the endoplasmic reticulum of hepatocytes. Selectively methylates S-centered nucleophiles from metabolites such as hydrogen sulfide and dithiothreitol.

Subcellular location. Endoplasmic reticulum membrane. Lipid droplet. Microsome. Cytoplasm. Cytosol.

Tissue specificity. Expressed in the liver.

Miscellaneous. Methylates drugs such as 7alpha-thiospironolactone, L-penicillamine and captopril.

Similarity. Belongs to the methyltransferase superfamily.

RefSeq proteins (1): NP_689850* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013216	Methyltransf_11	Domain
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily
IPR052356	Thiol_S-MT	Family

Pfam: PF08241

Catalyzed reactions (Rhea), 1 shown:

• a thiol + S-adenosyl-L-methionine = a methyl thioether + S-adenosyl-L-homocysteine + H(+) (RHEA:18277)

UniProt features (3 total): signal peptide 1, chain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UX53-F1	94.94	0.92

Functional residue map

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

Mutagenesis-validated functional residues (1):

Position	Phenotype
98	loss of catalytic activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 79 (showing top): GCANCTGNY_MYOD_Q6, CAGCTG_AP4_Q5, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_10D_UP, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_16D_UP, GOBP_METHYLATION, AP4_01, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_8D_UP, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOCC_ORGANELLE_SUBCOMPARTMENT, GOMF_S_ADENOSYLMETHIONINE_DEPENDENT_METHYLTRANSFERASE_ACTIVITY, YOSHIMURA_MAPK8_TARGETS_UP, GOMF_TRANSFERASE_ACTIVITY_TRANSFERRING_ONE_CARBON_GROUPS, CERVERA_SDHB_TARGETS_2, WAKABAYASHI_ADIPOGENESIS_PPARG_RXRA_BOUND_8D, GOCC_LIPID_DROPLET

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

GO Molecular Function (4): S-adenosylmethionine-dependent methyltransferase activity (GO:0008757), thiol S-methyltransferase activity (GO:0018708), methyltransferase activity (GO:0008168), transferase activity (GO:0016740)

GO Cellular Component (6): endoplasmic reticulum membrane (GO:0005789), lipid droplet (GO:0005811), cytosol (GO:0005829), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoplasm	2
metabolic process	1
methyltransferase activity	1
S-methyltransferase activity	1
S-adenosylmethionine-dependent methyltransferase activity	1
transferase activity, transferring one-carbon groups	1
catalytic activity	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1040 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMT1B	METTL25	Q8N6Q8	749
TMT1B	METTL9	Q9H1A3	662
TMT1B	METTL2B	Q6P1Q9	632
TMT1B	METTL8	Q9H825	612
TMT1B	EEF1AKMT2	Q5JPI9	594
TMT1B	METTL13	Q8N6R0	582
TMT1B	HSD17B11	Q8NBQ5	477
TMT1B	AUP1	Q9Y679	472
TMT1B	GPAT4	Q86UL3	450
TMT1B	METTL27	Q8N6F8	447
TMT1B	METTL17	Q9H7H0	445
TMT1B	FAF2	Q96CS3	419
TMT1B	METTL24	Q5JXM2	413
TMT1B	METTL6	Q8TCB7	410
TMT1B	CCNB1	P14635	404

IntAct

21 interactions, top by confidence:

A	B	Type	Score
FAM241A	NRP1	psi-mi:“MI:0914”(association)	0.530
IRGC	RAP1GDS1	psi-mi:“MI:0914”(association)	0.530
TMT1B		psi-mi:“MI:0915”(physical association)	0.370
GRPR	GPR89A	psi-mi:“MI:0914”(association)	0.350
RTN4	SCAMP1	psi-mi:“MI:0914”(association)	0.350
ADAM30	PLXNA2	psi-mi:“MI:0914”(association)	0.350
IRGC	RPS6KA3	psi-mi:“MI:0914”(association)	0.350
	DENND11	psi-mi:“MI:0914”(association)	0.350
LDLRAD1	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CLEC2D	TMEM120B	psi-mi:“MI:0914”(association)	0.350
RUSF1	TMEM120B	psi-mi:“MI:0914”(association)	0.350
ADAM30	MBTPS2	psi-mi:“MI:0914”(association)	0.350
IL2RA	LTN1	psi-mi:“MI:0914”(association)	0.350
FFAR1	SLC12A8	psi-mi:“MI:0914”(association)	0.350
CHRM4	EXOC5	psi-mi:“MI:0914”(association)	0.350
HPN	DDX39A	psi-mi:“MI:0914”(association)	0.350
SLC2A5	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC7A4	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (28): METTL7B (Affinity Capture-MS), METTL7B (Affinity Capture-MS), METTL7B (Affinity Capture-MS), METTL7B (Affinity Capture-MS), METTL7B (Affinity Capture-MS), METTL7B (Affinity Capture-MS), METTL7B (Affinity Capture-MS), METTL7B (Affinity Capture-MS), METTL7B (Proximity Label-MS), METTL7B (Affinity Capture-MS), METTL7B (Affinity Capture-MS), METTL7B (Affinity Capture-MS), METTL7B (Affinity Capture-MS), METTL7B (Affinity Capture-MS), METTL7B (Affinity Capture-MS)

ESM2 similar proteins: A4IG53, A5PJK1, B1WC86, D2I2M6, F1N2K1, O95479, P58242, P70665, P82450, P98192, Q05AK6, Q08BG1, Q0P5H1, Q1JPD2, Q1LWG4, Q4V7R2, Q53F39, Q5R748, Q5RET5, Q5RFU0, Q5ZK82, Q61139, Q640M6, Q641Z7, Q658P3, Q6L5F5, Q6UX53, Q6ZT21, Q7G7C7, Q80XL7, Q8BMD6, Q8C7K6, Q8NBM8, Q8R2R1, Q8WTR4, Q92485, Q95KC9, Q99PR0, Q9D0Z3, Q9ES71

Diamond homologs: A0A8D5M692, A0A8X8M4W6, A0KIF6, A1AB99, A1K8U5, A1TP97, A1WVM4, A3PFL1, A4G5P1, A4SPN7, A4T0W0, A4VGE5, A4WVR7, A6UYW3, A6W0X8, A7MPA9, A7ZLX5, A8A072, A8LNK7, A9BVK1, B0UPF4, B1IRU1, B1LF96, B1LXF6, B1XEA7, B2IAI0, B2SHS9, B3PI89, B3QLI9, B5Z1X6, B6IAS2, B7L7L9, B7LRD2, B7LZC1, B7MMY3, B7NIJ1, B7URP6, B8ISV4, B9JBE6, B9KQJ8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	2
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

91 predictions. Top by Δscore:

Variant	Effect	Δscore
12:55682229:G:GT	donor_gain	1.0000
12:55682238:A:T	donor_gain	1.0000
12:55682248:GACCG:G	donor_gain	1.0000
12:55682249:ACCG:A	donor_gain	1.0000
12:55682250:CCG:C	donor_gain	1.0000
12:55682253:G:GG	donor_gain	1.0000
12:55682254:T:G	donor_loss	1.0000
12:55682216:G:GT	donor_gain	0.9900
12:55682251:CG:C	donor_gain	0.9900
12:55682252:GG:G	donor_gain	0.9900
12:55683811:AG:A	acceptor_gain	0.9900
12:55683812:GG:G	acceptor_gain	0.9900
12:55682217:A:T	donor_gain	0.9800
12:55683812:GGGA:G	acceptor_gain	0.9800
12:55683807:TCCCA:T	acceptor_loss	0.9700
12:55683809:CCA:C	acceptor_loss	0.9700
12:55683811:A:T	acceptor_loss	0.9700
12:55683812:G:GT	acceptor_loss	0.9700
12:55682233:TCCG:T	donor_gain	0.9300
12:55683811:A:AG	acceptor_gain	0.9300
12:55683811:AGG:A	acceptor_gain	0.9300
12:55683812:G:GG	acceptor_gain	0.9300
12:55683812:GGG:G	acceptor_gain	0.9300
12:55682234:C:A	donor_gain	0.9100
12:55682250:CCGGT:C	donor_gain	0.9100
12:55682251:CGGTA:C	donor_gain	0.9100
12:55682252:GGTAA:G	donor_gain	0.9100
12:55682253:GTAAG:G	donor_gain	0.9100
12:55683810:CAGGG:C	acceptor_gain	0.9100
12:55683811:AGGGA:A	acceptor_gain	0.9100

AlphaMissense

1591 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:55682006:C:A	N84K	0.978
12:55682006:C:G	N84K	0.978
12:55682013:T:C	F87L	0.972
12:55682015:C:A	F87L	0.972
12:55682015:C:G	F87L	0.972
12:55682042:C:G	C96W	0.968
12:55682040:T:C	C96R	0.962
12:55682181:T:C	C143R	0.960
12:55683897:T:A	W195R	0.957
12:55683897:T:C	W195R	0.957
12:55682016:T:G	Y88D	0.956
12:55683839:T:A	H175Q	0.955
12:55683839:T:G	H175Q	0.955
12:55682061:T:C	F103L	0.953
12:55682063:T:A	F103L	0.953
12:55682063:T:G	F103L	0.953
12:55683835:A:T	E174V	0.953
12:55682035:T:A	V94D	0.952
12:55683963:T:C	F217L	0.952
12:55683965:C:A	F217L	0.952
12:55683965:C:G	F217L	0.952
12:55681999:G:A	G82E	0.950
12:55682196:T:C	C148R	0.950
12:55682008:T:C	F85S	0.948
12:55681993:G:A	G80E	0.946
12:55682047:A:G	D98G	0.946
12:55682198:C:G	C148W	0.945
12:55681919:A:C	K55N	0.942
12:55681919:A:T	K55N	0.942
12:55683878:G:C	Q188H	0.941

dbSNP variants (sampled 300 via entrez): RS1000670218 (12:55681398 T>A,C), RS1000839579 (12:55682317 C>T), RS1000898878 (12:55684419 T>C), RS1001378070 (12:55684306 C>T), RS1002349720 (12:55682714 T>C), RS1002350993 (12:55684231 C>T), RS1002949832 (12:55683915 G>A), RS1004423310 (12:55681432 C>A), RS1005475434 (12:55682768 A>C), RS1006201612 (12:55684182 T>C,G), RS1006465765 (12:55683010 A>C), RS1006890210 (12:55683955 A>G,T), RS1006918177 (12:55682240 A>G), RS1007749200 (12:55684546 G>A), RS1008217756 (12:55684804 A>G,T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010002_217	Refractive error	6.000000e-174

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression	3
Estradiol	increases expression, affects cotreatment, decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
pirinixic acid	affects binding, decreases expression, increases activity	1
deoxynivalenol	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
ferrous chloride	decreases expression	1
hydroquinone	decreases expression	1
nivalenol	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects response to substance	1
entinostat	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
belinostat	decreases expression	1
ICG 001	decreases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	increases expression, affects cotreatment	1
incobotulinumtoxinA	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Temozolomide	decreases expression	1
Leflunomide	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects cotreatment, increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression	1
Quercetin	decreases expression	1
Silicon Dioxide	decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1

Clinical trials (associated diseases)

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