TFB2M

Summary

TFB2M (transcription factor B2, mitochondrial, HGNC:18559) is a protein-coding gene on chromosome 1q44, encoding Dimethyladenosine transferase 2, mitochondrial (Q9H5Q4). S-adenosyl-L-methionine-dependent rRNA methyltransferase which may methylate two specific adjacent adenosines in the loop of a conserved hairpin near the 3’-end of 12S mitochondrial rRNA. It is a selective cancer dependency (DepMap: 68.3% of cell lines).

Enables mitochondrial transcription factor activity. Involved in transcription initiation at mitochondrial promoter. Located in mitochondrial nucleoid.

Source: NCBI Gene 64216 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 85 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 68.3% of screened cell lines
• MANE Select transcript: NM_022366

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18559
Approved symbol	TFB2M
Name	transcription factor B2, mitochondrial
Location	1q44
Locus type	gene with protein product
Status	Approved
Aliases	FLJ23182, FLJ22661, Hkp1
Ensembl gene	ENSG00000162851
Ensembl biotype	protein_coding
OMIM	607055
Entrez	64216

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 9 protein_coding

ENST00000366514, ENST00000873621, ENST00000873622, ENST00000873623, ENST00000873624, ENST00000873625, ENST00000936096, ENST00000936097, ENST00000936098

RefSeq mRNA: 1 — MANE Select: NM_022366 NM_022366

CCDS: CCDS1627

Canonical transcript exons

ENST00000366514 — 8 exons

Exon	Start	End
ENSE00001069213	246564346	246564434
ENSE00001069217	246544521	246544681
ENSE00001069221	246557381	246557534
ENSE00001441895	246540561	246541202
ENSE00001441896	246565826	246566261
ENSE00003468747	246551213	246551302
ENSE00003471911	246548545	246548607
ENSE00003576579	246556573	246556721

Expression profiles

Bgee: expression breadth ubiquitous, 272 present calls, max score 95.19.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.0315 / max 199.4382, expressed in 1797 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
18481	8.9047	1740
18480	8.1269	1722

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	95.19	gold quality
oocyte	CL:0000023	92.32	gold quality
palpebral conjunctiva	UBERON:0001812	90.73	gold quality
right adrenal gland	UBERON:0001233	89.72	gold quality
right adrenal gland cortex	UBERON:0035827	89.68	gold quality
biceps brachii	UBERON:0001507	89.40	gold quality
tibia	UBERON:0000979	89.02	gold quality
left adrenal gland	UBERON:0001234	88.78	gold quality
right lobe of liver	UBERON:0001114	88.37	gold quality
parietal pleura	UBERON:0002400	88.31	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	88.10	gold quality
deltoid	UBERON:0001476	88.09	gold quality
left adrenal gland cortex	UBERON:0035825	88.07	gold quality
gastrocnemius	UBERON:0001388	88.05	gold quality
adrenal cortex	UBERON:0001235	88.04	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.94	gold quality
adrenal gland	UBERON:0002369	87.77	gold quality
oral cavity	UBERON:0000167	87.73	gold quality
nephron tubule	UBERON:0001231	87.53	gold quality
muscle of leg	UBERON:0001383	87.45	gold quality
mucosa of sigmoid colon	UBERON:0004993	86.96	gold quality
liver	UBERON:0002107	86.82	gold quality
adrenal tissue	UBERON:0018303	86.68	gold quality
pleura	UBERON:0000977	86.52	gold quality
muscle organ	UBERON:0001630	86.50	gold quality
colonic mucosa	UBERON:0000317	86.33	gold quality
skin of hip	UBERON:0001554	86.22	gold quality
tibialis anterior	UBERON:0001385	86.10	gold quality
gingival epithelium	UBERON:0001949	85.92	gold quality
upper leg skin	UBERON:0004262	85.79	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	133.32
E-ANND-3	yes	3.67

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFE2L2, NRF1, SP1

miRNA regulators (miRDB)

24 targeting TFB2M, 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-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-1305	99.91	71.43	3443
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-4696	99.48	67.48	1040
HSA-MIR-4263	99.18	69.25	2236
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-4764-5P	98.88	65.53	894
HSA-MIR-3166	98.24	66.63	1223
HSA-MIR-93-3P	98.15	66.65	1309
HSA-MIR-1279	97.83	67.50	1898
HSA-MIR-6888-5P	95.89	63.78	831
HSA-MIR-548AD-3P	94.39	66.04	350

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 68.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 16)

• This transcription factor activates transcription of human mitochondrial DNA. (PMID:12068295)
• Distinct, but possibly coordinated functions of mtTFB1 and mtTFB2 in mitochondrial gene expression and biogenesis. (PMID:17557812)
• This study suggested that DNA variants in TFB2M did not contribute to the risk for parkinson disease. (PMID:18980857)
• determined the variation in the TFAM, TFB1M, and TFB2M genes in cardiac hypertrophy (PMID:19096125)
• rRNA methyltransferase activity is necessary for induction of mitochondrial biogenesis by TFB1M, but not TFB2M. (PMID:19417006)
• Promoter-independent DNA conformation-dependent transcription required TFB2M. (PMID:19624753)
• The mRNA levels of TFB1M and TFB2M are influenced by endurance training (PMID:19681768)
• only two essential initiation factors, TFAM and TFB2M, and two promoters, LSP and HSP1, are required to drive transcription of the mitochondrial genome (PMID:20410300)
• The results reveal the organization of TFAM, POLRMT and TFB2M around the light-strand promoter and represent the first structural characterization of the entire mitochondrial transcriptional initiation complex. (PMID:24413562)
• demonstrate that a complex composed of TFAM and POLRMT was readily formed at the promoter but alone was insufficient for promoter melting, which only occurred when TFB2M joined the complex (PMID:28028173)
• Study reports crystal structures of human mitochondrial transcription initiation complexes assembled on both light and heavy strand promoters. The structures reveal how transcription factors TFAM and TFB2M assist mitochondrial RNA polymerase to achieve promoter-dependent initiation. (PMID:29149603)
• a rare homozygous c.790C>T (His264Tyr) variation in TFB2M gene in two Korean siblings with autism spectrum disorder by whole-exome sequencing, is reported. (PMID:30414672)
• Over-expression of TFB2M facilitates cell growth and metastasis via activating ROS-Akt-NF-kappaB signalling in hepatocellular carcinoma. (PMID:32174027)
• Phosphorylation of mitochondrial transcription factor B2 controls mitochondrial DNA binding and transcription. (PMID:32505352)
• TFB2M and POLRMT are essential for mammalian mitochondrial DNA replication. (PMID:34744028)
• Mitochondrial transcription factor B2 overexpression increases M2 macrophage infiltration via cytosolic mitochondrial DNA-stimulated Interleukin-6 secretion in ovarian cancer. (PMID:35577351)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tfb2m	ENSDARG00000074756
mus_musculus	Tfb2m	ENSMUSG00000026492
rattus_norvegicus	Tfb2m	ENSRNOG00000002695

Paralogs (2): TFB1M (ENSG00000029639), DIMT1 (ENSG00000086189)

Protein

Protein identifiers

Dimethyladenosine transferase 2, mitochondrial — Q9H5Q4 (reviewed: Q9H5Q4)

Alternative names: Hepatitis C virus NS5A-transactivated protein 5, Mitochondrial 12S rRNA dimethylase 2, Mitochondrial transcription factor B2, S-adenosylmethionine-6-N’, N’-adenosyl(rRNA) dimethyltransferase 2

All UniProt accessions (1): Q9H5Q4

UniProt curated annotations — full annotation on UniProt →

Function. S-adenosyl-L-methionine-dependent rRNA methyltransferase which may methylate two specific adjacent adenosines in the loop of a conserved hairpin near the 3’-end of 12S mitochondrial rRNA. Component of the mitochondrial transcription initiation complex, composed at least of TFB2M, TFAM and POLRMT that is required for basal transcription of mitochondrial DNA. In this complex, TFAM recruits POLRMT to a specific promoter whereas TFB2M induces structural changes in POLRMT to enable promoter opening and trapping of the DNA non-template strand. Stimulates transcription independently of the methyltransferase activity.

Subunit / interactions. Homodimer. Component of the mitochondrial transcription initiation complex, composed at least of TFB2M, TFAM and POLRMT. In this complex TFAM recruits POLRMT to the promoter whereas TFB2M induces structural changes in POLRMT to enable promoter opening and trapping of the DNA non-template strand. Interacts with mitochondrial RNA polymerase POLRMT. Interacts with TFAM.

Subcellular location. Mitochondrion.

Tissue specificity. Ubiquitously expressed.

Induction. By the nuclear respiratory factors NRF1 and NRF2/GABPB2 and PGC-1 coactivators.

Similarity. Belongs to the class I-like SAM-binding methyltransferase superfamily. rRNA adenine N(6)-methyltransferase family. KsgA subfamily.

RefSeq proteins (1): NP_071761* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001737	KsgA/Erm	Family
IPR020598	rRNA_Ade_methylase_Trfase_N	Domain
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily

Pfam: PF00398

Catalyzed reactions (Rhea), 1 shown:

• adenosine in rRNA + S-adenosyl-L-methionine = N(6)-methyladenosine in rRNA + S-adenosyl-L-homocysteine + H(+) (RHEA:58728)

UniProt features (45 total): helix 16, strand 11, sequence variant 4, mutagenesis site 3, turn 3, binding site 3, region of interest 2, transit peptide 1, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
6ERO	X-RAY DIFFRACTION	1.75
9MN7	ELECTRON MICROSCOPY	2.65
9MN6	ELECTRON MICROSCOPY	2.71
9MN5	ELECTRON MICROSCOPY	3.04
9MN4	ELECTRON MICROSCOPY	3.05
9R96	ELECTRON MICROSCOPY	3.1
9GZO	ELECTRON MICROSCOPY	3.15
9R95	ELECTRON MICROSCOPY	3.2
9GZM	ELECTRON MICROSCOPY	3.4
9GZN	ELECTRON MICROSCOPY	3.5
6ERQ	X-RAY DIFFRACTION	4.5
6ERP	X-RAY DIFFRACTION	4.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H5Q4-F1	80.89	0.64

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 (3): 75; 124; 150

Mutagenesis-validated functional residues (3):

Position	Phenotype
105	abolishes methyltransferase activity.
330	impairs transcription initiation; when associated with a-331.
331	impairs transcription initiation; when associated with a-330.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-163282	Mitochondrial transcription initiation
R-HSA-2151201	Transcriptional activation of mitochondrial biogenesis
R-HSA-1592230	Mitochondrial biogenesis
R-HSA-1852241	Organelle biogenesis and maintenance
R-HSA-74160	Gene expression (Transcription)
R-HSA-75944	Transcription from mitochondrial promoters

MSigDB gene sets: 162 (showing top): GOBP_RIBOSOME_BIOGENESIS, HORIUCHI_WTAP_TARGETS_DN, GGCNKCCATNK_UNKNOWN, GOBP_RNA_METHYLATION, GOBP_RNA_MODIFICATION, GGAANCGGAANY_UNKNOWN, WCTCNATGGY_UNKNOWN, FUJIWARA_PARK2_HEPATOCYTE_PROLIFERATION_UP, GOBP_MITOCHONDRIAL_RNA_METABOLIC_PROCESS, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, PU1_Q6, DODD_NASOPHARYNGEAL_CARCINOMA_UP, ELK1_01, POU3F2_02, RGAGGAARY_PU1_Q6

GO Biological Process (6): mitochondrial transcription (GO:0006390), transcription initiation at mitochondrial promoter (GO:0006391), rRNA methylation (GO:0031167), rRNA modification (GO:0000154), rRNA processing (GO:0006364), methylation (GO:0032259)

GO Molecular Function (6): rRNA (adenine-N6,N6-)-dimethyltransferase activity (GO:0000179), RNA binding (GO:0003723), rRNA (adenine-N6-)-methyltransferase activity (GO:0008988), mitochondrial transcription factor activity (GO:0034246), methyltransferase activity (GO:0008168), transferase activity (GO:0016740)

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), mitochondrial nucleoid (GO:0042645)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Transcription from mitochondrial promoters	1
Mitochondrial biogenesis	1
Organelle biogenesis and maintenance	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrion	4
mitochondrial RNA metabolic process	2
mitochondrial transcription	2
N-methyltransferase activity	2
rRNA (adenine) methyltransferase activity	2
DNA-templated transcription	1
mitochondrial gene expression	1
DNA-templated transcription initiation	1
rRNA modification	1
RNA methylation	1
rRNA processing	1
RNA modification	1
RNA processing	1
rRNA metabolic process	1
ribosome biogenesis	1
metabolic process	1
nucleic acid binding	1
mitochondrial single-subunit type RNA polymerase binding	1
mitochondrial promoter sequence-specific DNA binding	1
transcription regulator activity	1
transferase activity, transferring one-carbon groups	1
catalytic activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
intracellular organelle lumen	1
mitochondrial matrix	1
nucleoid	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

3397 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TFB2M	POLRMT	O00411	999
TFB2M	TFAM	Q00059	997
TFB2M	MTERF1	Q99551	858
TFB2M	TEFM	Q96QE5	770
TFB2M	TWNK	Q96RR1	749
TFB2M	MTERF3	Q96E29	722
TFB2M	GABPB1	Q06547	698
TFB2M	POLG	P54098	686
TFB2M	SP2	Q02086	677
TFB2M	SSBP1	Q04837	638
TFB2M	PPARGC1A	Q9UBK2	635
TFB2M	MTERF2	Q49AM1	621
TFB2M	POLG2	Q9UHN1	616
TFB2M	NRF1	Q16656	605
TFB2M	MRPL12	P52815	597

IntAct

114 interactions, top by confidence:

A	B	Type	Score
POLRMT	MRPL12	psi-mi:“MI:0914”(association)	0.800
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
POLRMT	TFAM	psi-mi:“MI:0915”(physical association)	0.560
POLRMT	TFAM	psi-mi:“MI:0914”(association)	0.560
TMEM9	ESYT2	psi-mi:“MI:0914”(association)	0.530
GYPB	TCAF2	psi-mi:“MI:0914”(association)	0.530
SLC15A1	METTL15	psi-mi:“MI:0914”(association)	0.530
CD70	METTL15	psi-mi:“MI:0914”(association)	0.530
APLNR	SLC33A1	psi-mi:“MI:0914”(association)	0.530
NPTN	TNPO2	psi-mi:“MI:0914”(association)	0.530
TFAM	TFB2M	psi-mi:“MI:0407”(direct interaction)	0.440
TFB2M	ATP5F1B	psi-mi:“MI:0915”(physical association)	0.400
	POLRMT	psi-mi:“MI:0915”(physical association)	0.400
Nup188	RPS3	psi-mi:“MI:0914”(association)	0.350
Cep131	WBP2	psi-mi:“MI:0914”(association)	0.350
Nek2	WDR46	psi-mi:“MI:0914”(association)	0.350
Tnpo1	CCHCR1	psi-mi:“MI:0914”(association)	0.350
Ppp2ca	DKFZP586J0619	psi-mi:“MI:0914”(association)	0.350
TUBG1	DPM1	psi-mi:“MI:0914”(association)	0.350
Gpkow	BDP1	psi-mi:“MI:0914”(association)	0.350
Samm50	ZC3H18	psi-mi:“MI:0914”(association)	0.350
RAB4B	NSF	psi-mi:“MI:0914”(association)	0.350
GAR1	TAF1	psi-mi:“MI:0914”(association)	0.350
M2	ESYT2	psi-mi:“MI:0914”(association)	0.350
MKI67	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (114): TFB2M (Affinity Capture-MS), TFB2M (Affinity Capture-MS), TFB2M (Affinity Capture-MS), TFB2M (Affinity Capture-MS), TFB2M (Affinity Capture-MS), TFB2M (Affinity Capture-MS), TFB2M (Affinity Capture-MS), TFB2M (Affinity Capture-MS), TFB2M (Affinity Capture-MS), TFB2M (Affinity Capture-MS), TFB2M (Affinity Capture-MS), TFB2M (Affinity Capture-MS), TFB2M (Affinity Capture-MS), TFB2M (Affinity Capture-MS), TFB2M (Affinity Capture-MS)

ESM2 similar proteins: B0S6U7, B0S8I0, B5DF07, B5X2B8, D2GU20, E7FCP8, F4J2K2, F6QXW0, G3GXG9, O15091, O75417, O75616, O82626, P97874, Q28ES8, Q2KHZ2, Q32LB9, Q32LD4, Q32NV1, Q3T0J9, Q3T131, Q3TL26, Q4R366, Q5R6Y0, Q5U2T7, Q63159, Q69ZS7, Q6AXM7, Q6DCC6, Q6NZQ2, Q6PGG6, Q6ZPR6, Q7Z2Z2, Q80Y81, Q811S9, Q84MA1, Q8BMS4, Q8C0D5, Q8C7H1, Q8CI11

Diamond homologs: A1B0G4, A3PJZ3, A4WRK3, A4YT90, A5EIA8, A5VPL7, A6U7I6, A6X265, A7IJ80, A8HVI9, A9IRW8, A9MA55, B0CL06, B1LVB8, B2S4U1, B3PUU6, B3Q9S4, B5ZWD8, B9JUV4, B9KST5, C0RI23, C3M9C2, O22268, P43038, P59157, Q07LF4, Q11HG9, Q135P2, Q1GT31, Q1MJ01, Q1QKW0, Q215S4, Q28RD6, Q2FSA9, Q2G9Z2, Q2IX80, Q2KA84, Q2N8W9, Q2W0V3, Q2YN15

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
NFE2L2	“up-regulates quantity by expression”	TFB2M	“transcriptional regulation”
NRF1	“up-regulates quantity by expression”	TFB2M	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	48
Likely benign	16
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1430 predictions. Top by Δscore:

Variant	Effect	Δscore
1:246541199:TGAA:T	acceptor_gain	1.0000
1:246541203:C:CC	acceptor_gain	1.0000
1:246548540:CTTA:C	donor_loss	1.0000
1:246548541:TTACC:T	donor_loss	1.0000
1:246548542:TA:T	donor_loss	1.0000
1:246548543:A:AC	donor_gain	1.0000
1:246548543:A:AG	donor_loss	1.0000
1:246548543:AC:A	donor_gain	1.0000
1:246548544:C:CC	donor_gain	1.0000
1:246548544:CC:C	donor_gain	1.0000
1:246548544:CCCT:C	donor_gain	1.0000
1:246548544:CCCTA:C	donor_gain	1.0000
1:246548605:CTC:C	acceptor_gain	1.0000
1:246548608:C:CC	acceptor_gain	1.0000
1:246548608:CTGG:C	acceptor_loss	1.0000
1:246548609:T:G	acceptor_loss	1.0000
1:246564347:T:TA	donor_gain	1.0000
1:246541198:ATGAA:A	acceptor_gain	0.9900
1:246541200:GAA:G	acceptor_gain	0.9900
1:246544514:TAC:T	donor_loss	0.9900
1:246544515:ACTC:A	donor_loss	0.9900
1:246544516:CTC:C	donor_loss	0.9900
1:246544517:T:TA	donor_loss	0.9900
1:246544518:C:CC	donor_loss	0.9900
1:246544519:A:AC	donor_gain	0.9900
1:246544520:C:CC	donor_gain	0.9900
1:246544679:TTC:T	acceptor_gain	0.9900
1:246544679:TTCC:T	acceptor_loss	0.9900
1:246544680:TCC:T	acceptor_loss	0.9900
1:246544681:CCTGG:C	acceptor_loss	0.9900

AlphaMissense

2590 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:246551255:A:C	S251R	0.981
1:246551255:A:T	S251R	0.981
1:246551257:T:G	S251R	0.981
1:246564361:A:C	F129L	0.976
1:246564361:A:T	F129L	0.976
1:246564363:A:G	F129L	0.976
1:246548590:A:C	F271L	0.974
1:246548590:A:T	F271L	0.974
1:246548592:A:G	F271L	0.974
1:246551253:A:T	V252D	0.973
1:246564434:C:T	G105D	0.973
1:246541113:A:G	F370S	0.972
1:246544616:A:C	F308L	0.972
1:246544616:A:T	F308L	0.972
1:246544618:A:G	F308L	0.972
1:246544561:A:G	C327R	0.971
1:246557390:A:G	W183R	0.969
1:246557390:A:T	W183R	0.969
1:246541063:A:G	W387R	0.965
1:246541063:A:T	W387R	0.965
1:246541100:A:C	F374L	0.965
1:246541100:A:T	F374L	0.965
1:246541102:A:G	F374L	0.965
1:246544524:A:G	L339S	0.965
1:246556616:C:T	G221E	0.965
1:246556616:C:A	G221V	0.962
1:246564383:G:T	A122E	0.962
1:246564428:C:A	G107V	0.961
1:246544565:C:A	K325N	0.960
1:246544565:C:G	K325N	0.960

dbSNP variants (sampled 300 via entrez): RS1000025298 (1:246560967 G>A), RS1000046725 (1:246560603 A>G,T), RS1000143870 (1:246567011 C>T), RS1000245858 (1:246556084 C>T), RS1000266435 (1:246566272 C>A,T), RS1000379082 (1:246546098 G>A), RS1000477797 (1:246556364 A>G), RS1000523926 (1:246560324 C>T), RS1000556766 (1:246560455 T>C,G), RS1000603225 (1:246564207 T>C), RS1000796288 (1:246546451 C>G,T), RS1000855418 (1:246567091 G>A), RS1001027613 (1:246562007 C>T), RS1001149908 (1:246541874 C>G), RS1001186148 (1:246546693 C>A,T)

Disease associations

OMIM: gene MIM:607055 | 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
GCST008103_176	Bipolar disorder	8.000000e-06
GCST009391_828	Metabolite levels	4.000000e-06
GCST012131_1	hemolysis of donated blood (osmotic)	4.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006523	symmetrical dimethylarginine measurement
EFO:0009473	hemolysis

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067169 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.63	Kd	233	nM	CHEMBL3752910
6.63	ED50	233	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149952: Binding affinity to human TFB2M incubated for 45 mins by Kinobead based pull down assay	kd	0.2330	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	affects cotreatment, decreases expression	4
sodium arsenite	decreases expression, increases abundance, increases expression	2
Leflunomide	decreases expression	2
Tobacco Smoke Pollution	increases expression	2
Tretinoin	decreases expression	2
dicrotophos	decreases expression	1
cinobufagin	decreases expression	1
perfluorooctanoic acid	increases expression	1
zinc chromate	increases abundance, increases expression	1
manganese chloride	increases abundance, increases expression	1
chromium hexavalent ion	increases abundance, increases expression	1
CGP 52608	affects binding, increases reaction	1
ICG 001	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases abundance, increases expression	1
Hexachlorocyclohexane	increases expression	1
Cadmium	increases abundance, increases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Coal	decreases expression, increases abundance	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	decreases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Lead	increases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Manganese	increases abundance, increases expression	1
Ribonucleotides	affects binding	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652994	Binding	Binding affinity to human TFB2M incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E0QQ	Ubigene HeLa TFB2M KO	Cancer cell line	Female

Clinical trials (associated diseases)

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