TFB1M

Summary

TFB1M (transcription factor B1, mitochondrial, HGNC:17037) is a protein-coding gene on chromosome 6q25.3, encoding Dimethyladenosine transferase 1, mitochondrial (Q8WVM0). Mitochondrial methyltransferase which uses S-adenosyl methionine to dimethylate two highly conserved adjacent adenosine residues (A1583 and A1584) within the loop of helix 45 at the 3-prime end of 12S rRNA, thereby regulating the assembly or stability of the small subunit of the…. It is a selective cancer dependency (DepMap: 18.3% of cell lines).

The protein encoded by this gene is a dimethyltransferase that methylates the conserved stem loop of mitochondrial 12S rRNA. The encoded protein also is part of the basal mitochondrial transcription complex and is necessary for mitochondrial gene expression. The methylation and transcriptional activities of this protein are independent of one another. Variations in this gene may influence the severity of aminoglycoside-induced deafness (AID).

Source: NCBI Gene 51106 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 167 total
• Cancer dependency (DepMap): dependent in 18.3% of screened cell lines
• MANE Select transcript: NM_016020

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17037
Approved symbol	TFB1M
Name	transcription factor B1, mitochondrial
Location	6q25.3
Locus type	gene with protein product
Status	Approved
Aliases	mtTFB, CGI-75
Ensembl gene	ENSG00000029639
Ensembl biotype	protein_coding
OMIM	607033
Entrez	51106

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 9 protein_coding, 8 protein_coding_CDS_not_defined

ENST00000367166, ENST00000466349, ENST00000468889, ENST00000470239, ENST00000475849, ENST00000480390, ENST00000487586, ENST00000489874, ENST00000495806, ENST00000909436, ENST00000909437, ENST00000909438, ENST00000909439, ENST00000909440, ENST00000929539, ENST00000929540, ENST00000961151

RefSeq mRNA: 3 — MANE Select: NM_016020 NM_001350501, NM_001350502, NM_016020

CCDS: CCDS5248

Canonical transcript exons

ENST00000367166 — 7 exons

Exon	Start	End
ENSE00001443673	155256134	155258082
ENSE00003481994	155311188	155311339
ENSE00003485241	155296953	155297104
ENSE00003505395	155285158	155285277
ENSE00003561673	155314296	155314484
ENSE00003580497	155298477	155298585
ENSE00003599602	155260273	155260400

Expression profiles

Bgee: expression breadth ubiquitous, 261 present calls, max score 90.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.1262 / max 155.1186, expressed in 1774 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
76332	11.6368	1773
76329	0.2377	72
76333	0.2200	78
76334	0.0318	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland	UBERON:0001233	90.33	gold quality
right adrenal gland cortex	UBERON:0035827	90.13	gold quality
left adrenal gland	UBERON:0001234	90.01	gold quality
left adrenal gland cortex	UBERON:0035825	89.98	gold quality
adrenal cortex	UBERON:0001235	89.95	gold quality
left testis	UBERON:0004533	89.49	gold quality
adrenal tissue	UBERON:0018303	89.36	gold quality
adrenal gland	UBERON:0002369	89.25	gold quality
right testis	UBERON:0004534	88.90	gold quality
right lobe of liver	UBERON:0001114	88.54	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.43	gold quality
lower esophagus mucosa	UBERON:0035834	88.36	gold quality
testis	UBERON:0000473	88.18	gold quality
calcaneal tendon	UBERON:0003701	86.74	gold quality
mucosa of transverse colon	UBERON:0004991	86.58	gold quality
right lobe of thyroid gland	UBERON:0001119	86.50	gold quality
gastrocnemius	UBERON:0001388	86.41	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.37	gold quality
adenohypophysis	UBERON:0002196	86.18	gold quality
muscle of leg	UBERON:0001383	86.13	gold quality
spleen	UBERON:0002106	85.73	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.63	gold quality
heart left ventricle	UBERON:0002084	85.55	gold quality
sperm	CL:0000019	85.54	gold quality
left lobe of thyroid gland	UBERON:0001120	85.51	gold quality
cardiac ventricle	UBERON:0002082	85.37	gold quality
Brodmann (1909) area 9	UBERON:0013540	85.27	gold quality
esophagus mucosa	UBERON:0002469	85.22	gold quality
right uterine tube	UBERON:0001302	85.16	gold quality
metanephros cortex	UBERON:0010533	85.12	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.65

Regulation

Is transcription factor: no

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

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 18.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 12)

• This transcription factor activates transcription of human mitochondrial DNA. (PMID:12068295)
• Human mitochondrial transcription factor B1 methylates ribosomal RNA at a conserved stem-loop (PMID:12496758)
• TFB1 interacts with the C-terminal activation region of h-mtTFA and stimulates transcription independently of its RNA methyltransferase activity (PMID:12897151)
• TFB1M is a nuclear-encoded modifier gene for phenotypic expression of the deafness-associated homoplasmic A1555G mutation in the mitochondrial 12S rRNA gene. (PMID:15110318)
• Distinct, but possibly coordinated functions of mtTFB1 and mtTFB2 in mitochondrial gene expression and biogenesis. (PMID:17557812)
• This study suggested that DNA variants in TFB1M 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)
• The mRNA levels of TFB1M and TFB2M are influenced by endurance training (PMID:19681768)
• Deficiency in TFB1M and impaired mitochondrial function contribute to the pathogenesis of type 2 diabetes. (PMID:21195351)
• Loss of TFB1M results in mitochondrial dysfunction that leads to impaired insulin secretion and diabetes. (PMID:24916378)
• The suppression of transcription factor B1, mitochondrial protein (hsTFB1M) protein level or the overexpression of inactive hsTFB1M mutants resulted in decreased ATP production. (PMID:31251801)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tfb1m	ENSDARG00000040727
mus_musculus	Tfb1m	ENSMUSG00000036983
rattus_norvegicus	Tfb1m	ENSRNOG00000056223
drosophila_melanogaster	mtTFB1	FBGN0261381
caenorhabditis_elegans	tfbm-1	WBGENE00020189

Paralogs (2): DIMT1 (ENSG00000086189), TFB2M (ENSG00000162851)

Protein

Protein identifiers

Dimethyladenosine transferase 1, mitochondrial — Q8WVM0 (reviewed: Q8WVM0)

Alternative names: Mitochondrial 12S rRNA dimethylase 1, Mitochondrial transcription factor B1, S-adenosylmethionine-6-N’, N’-adenosyl(rRNA) dimethyltransferase 1

All UniProt accessions (2): E5KTM5, Q8WVM0

UniProt curated annotations — full annotation on UniProt →

Function. Mitochondrial methyltransferase which uses S-adenosyl methionine to dimethylate two highly conserved adjacent adenosine residues (A1583 and A1584) within the loop of helix 45 at the 3-prime end of 12S rRNA, thereby regulating the assembly or stability of the small subunit of the mitochondrial ribosome. Also required for basal transcription of mitochondrial DNA, probably via its interaction with POLRMT and TFAM. Stimulates transcription independently of the methyltransferase activity.

Subunit / interactions. Interacts with mitochondrial RNA polymerase POLRMT. Interacts with TFAM. Bound to the maturing mtSSU until the late stages of assembly.

Subcellular location. Mitochondrion.

Tissue specificity. Ubiquitously expressed.

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

Miscellaneous. It has been proposed that variations in TFB1M may influence the clinical expression of aminoglycoside-induced deafness caused by the A1555G mutation in the mitochondrial 12S rRNA. However, this was later questioned as patients with the A1555G mutation had similar 12S rRNA methylation levels to controls.

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

RefSeq proteins (3): NP_001337430, NP_001337431, NP_057104* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001737	KsgA/Erm	Family
IPR011530	rRNA_adenine_dimethylase	Family
IPR020596	rRNA_Ade_Mease_Trfase_CS	Conserved_site
IPR020598	rRNA_Ade_methylase_Trfase_N	Domain
IPR023165	rRNA_Ade_diMease-like_C	Homologous_superfamily
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily

Pfam: PF00398

Catalyzed reactions (Rhea), 1 shown:

• adenosine(N)/adenosine(N+1) in rRNA + 4 S-adenosyl-L-methionine = N(6)-dimethyladenosine(N)/N(6)-dimethyladenosine(N+1) in rRNA + 4 S-adenosyl-L-homocysteine + 4 H(+) (RHEA:78527)

UniProt features (58 total): helix 21, strand 12, mutagenesis site 10, binding site 7, sequence variant 3, turn 2, transit peptide 1, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
8CSQ	ELECTRON MICROSCOPY	2.54
8CSR	ELECTRON MICROSCOPY	2.54
8CSP	ELECTRON MICROSCOPY	2.66
6AAX	X-RAY DIFFRACTION	2.99
6AJK	X-RAY DIFFRACTION	3
8CSU	ELECTRON MICROSCOPY	3.03
9G5B	ELECTRON MICROSCOPY	3.2
9H55	ELECTRON MICROSCOPY	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WVM0-F1	92.11	0.82

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 (7): 38; 63; 85; 86; 111; 112; 141

Mutagenesis-validated functional residues (10):

Position	Phenotype
65	abolishes methyltransferase activity, dna-binding and sam-binding. does not abolish transcription activator function.
85	inhibits rrna (adenine-n6,n6-)-dimethyltransferase activity.
86	inhibits rrna (adenine-n6,n6-)-dimethyltransferase activity.
111	inhibits rrna (adenine-n6,n6-)-dimethyltransferase activity.
112	inhibits rrna (adenine-n6,n6-)-dimethyltransferase activity.
141	does not affect sam-binding, dna-binding nor transcription activator function.
183	abolishes the interaction between 12s helix 45 and tfb1m; when associated with e-256 and e-257.
220	abolishes methyltransferase activity. does not affect sam-binding, dna-binding nor transcription activator function.
256	abolishes the interaction between 12s helix 45 and tfb1m; when associated with e-183 and e-257.
257	abolishes the interaction between 12s helix 45 and tfb1m; when associated with e-183 and e-256.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-2151201	Transcriptional activation of mitochondrial biogenesis
R-HSA-6793080	rRNA modification in the mitochondrion
R-HSA-1592230	Mitochondrial biogenesis
R-HSA-1852241	Organelle biogenesis and maintenance
R-HSA-72312	rRNA processing
R-HSA-8868766	rRNA processing in the mitochondrion
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 155 (showing top): GOBP_RIBOSOME_BIOGENESIS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, LANG_MYB_FAMILY_TARGETS, GOBP_RIBOSOME_ASSEMBLY, GOBP_RNA_METHYLATION, chr6q25, GOBP_RNA_MODIFICATION, GOBP_RIBOSOMAL_SMALL_SUBUNIT_BIOGENESIS, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GOBP_MITOCHONDRIAL_RNA_METABOLIC_PROCESS, GOBP_ORGANELLE_ASSEMBLY, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, TGANTCA_AP1_C, GFI1_01, RYTTCCTG_ETS2_B

GO Biological Process (6): rRNA modification (GO:0000154), transcription initiation at mitochondrial promoter (GO:0006391), rRNA methylation (GO:0031167), mitochondrial small ribosomal subunit assembly (GO:0180026), rRNA processing (GO:0006364), methylation (GO:0032259)

GO Molecular Function (8): rRNA (adenine-N6,N6-)-dimethyltransferase activity (GO:0000179), DNA binding (GO:0003677), RNA binding (GO:0003723), mitochondrial transcription factor activity (GO:0034246), S-adenosyl-L-methionine binding (GO:1904047), protein binding (GO:0005515), 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-5 pathways:

Category	Pathways
Mitochondrial biogenesis	1
rRNA processing in the mitochondrion	1
Organelle biogenesis and maintenance	1
Metabolism of RNA	1
rRNA processing	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrion	3
mitochondrial transcription	2
nucleic acid binding	2
rRNA processing	1
RNA modification	1
mitochondrial RNA metabolic process	1
DNA-templated transcription initiation	1
rRNA modification	1
RNA methylation	1
ribosomal small subunit assembly	1
mitochondrial ribosome assembly	1
RNA processing	1
rRNA metabolic process	1
ribosome biogenesis	1
metabolic process	1
N-methyltransferase activity	1
rRNA (adenine) methyltransferase activity	1
mitochondrial single-subunit type RNA polymerase binding	1
mitochondrial promoter sequence-specific DNA binding	1
transcription regulator activity	1
cation binding	1
sulfur compound binding	1
binding	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

2939 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TFB1M	POLRMT	O00411	999
TFB1M	TFAM	Q00059	995
TFB1M	GABPB1	Q06547	852
TFB1M	MTERF1	Q99551	818
TFB1M	MTERF3	Q96E29	773
TFB1M	TWNK	Q96RR1	740
TFB1M	SSBP1	Q04837	713
TFB1M	MTERF4	Q7Z6M4	677
TFB1M	POLG	P54098	673
TFB1M	NSUN4	Q96CB9	662
TFB1M	GTPBP3	Q969Y2	657
TFB1M	ERAL1	O75616	644
TFB1M	SCAF8	Q9UPN6	642
TFB1M	MRM3	Q9HC36	630
TFB1M	PPARGC1A	Q9UBK2	618

IntAct

77 interactions, top by confidence:

A	B	Type	Score
N	HNRNPR	psi-mi:“MI:0914”(association)	0.730
YWHAH	FAM83G	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
HSPD1	NUDT19	psi-mi:“MI:0914”(association)	0.710
BAIAP2	WASL	psi-mi:“MI:0914”(association)	0.550
TFAM	TFB1M	psi-mi:“MI:0915”(physical association)	0.540
TFAM	TFB1M	psi-mi:“MI:0407”(direct interaction)	0.540
MECP2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
TFB1M	HSPD1	psi-mi:“MI:0914”(association)	0.530
N	HNRNPDL	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530
YBEY	NME4	psi-mi:“MI:0914”(association)	0.530
H1-4	RRP8	psi-mi:“MI:0914”(association)	0.530
MRPL2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
MAGEB2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
RPL13	RRP8	psi-mi:“MI:0914”(association)	0.530
ZSCAN5A	KDM1A	psi-mi:“MI:0914”(association)	0.530
TFB1M	rl3_rl3l_human	psi-mi:“MI:0915”(physical association)	0.500
NDUFAB1	MIEF1	psi-mi:“MI:0915”(physical association)	0.490
TFB1M	POLRMT	psi-mi:“MI:0407”(direct interaction)	0.440
	TFB1M	psi-mi:“MI:0407”(direct interaction)	0.440
Rpl35	RPS6	psi-mi:“MI:0914”(association)	0.350
RPL10	RPS6	psi-mi:“MI:0914”(association)	0.350
Srp72		psi-mi:“MI:0914”(association)	0.350
AP4M1		psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350

BioGRID (100): TFB1M (Affinity Capture-RNA), TFB1M (Synthetic Growth Defect), TFB1M (Affinity Capture-MS), TFB1M (Affinity Capture-MS), TFB1M (Affinity Capture-MS), TFB1M (Affinity Capture-MS), TFB1M (Affinity Capture-MS), TFB1M (Affinity Capture-MS), TFB1M (Affinity Capture-MS), HSPD1 (Affinity Capture-MS), TFB1M (Affinity Capture-MS), DCAF8 (Affinity Capture-MS), TFB1M (Affinity Capture-MS), TFB1M (Affinity Capture-MS), TFB1M (Positive Genetic)

ESM2 similar proteins: A0A8I5ZNK2, A1L1L6, A2BHJ4, A8WGF4, O35142, O55029, O95803, P31016, P35605, P35606, P78352, Q2HJF8, Q4R4I8, Q5BJ41, Q5R495, Q5R4V9, Q5R664, Q5U4X8, Q5VQ78, Q5XH73, Q5ZM73, Q5ZM83, Q62108, Q640Z1, Q68FK8, Q6AXU9, Q6DJD3, Q6GQK9, Q6H8D5, Q6IR85, Q6NVC5, Q6NWV3, Q6P4W8, Q6P9R2, Q863I2, Q8BG51, Q8IXI2, Q8K3P5, Q8L828, Q8VEG6

Diamond homologs: A0LA32, A1B0G4, A1US65, A3PJZ3, A4IJB8, A4WRK3, A4YT90, A5EIA8, A5VPL7, A6U7I6, A6X265, A7IJ80, A8EZN3, A8GPG7, A8GT85, A8GXS7, A8HVI9, A8LI73, A9I5F2, A9IRW8, A9MA55, B0CL06, B1LVB8, B2S4U1, B3CPY6, B3PUU6, B3Q9S4, B4RBS4, B5ZWD8, B6JGM4, B9JUV4, B9KIG4, B9KST5, C0R5G4, C0RI23, C3M9C2, C3PPC3, C4K2J5, O05952, Q07LF4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 88 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Peptide chain elongation	8	15.6×	2e-06
Viral mRNA Translation	8	15.6×	2e-06
Formation of a pool of free 40S subunits	9	15.5×	1e-06
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	8	15.4×	2e-06
Mitochondrial ribosome-associated quality control	8	15.1×	2e-06
Selenocysteine synthesis	8	14.8×	2e-06
Eukaryotic Translation Termination	8	14.8×	2e-06
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	8	14.5×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	8	19.0×	5e-06
ribosomal small subunit biogenesis	5	14.6×	2e-03
translation	9	11.9×	2e-05
mitochondrial translation	5	11.1×	7e-03
rRNA processing	6	10.9×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	131
Likely benign	8
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

1767 predictions. Top by Δscore:

Variant	Effect	Δscore
6:155256482:A:AG	acceptor_gain	1.0000
6:155256483:G:GG	acceptor_gain	1.0000
6:155256483:GC:G	acceptor_gain	1.0000
6:155256483:GCT:G	acceptor_gain	1.0000
6:155256483:GCTT:G	acceptor_gain	1.0000
6:155256483:GCTTC:G	acceptor_gain	1.0000
6:155258079:CATT:C	acceptor_gain	1.0000
6:155258081:TT:T	acceptor_gain	1.0000
6:155258083:C:CC	acceptor_gain	1.0000
6:155260404:CGT:C	acceptor_gain	1.0000
6:155260406:T:TC	acceptor_gain	1.0000
6:155285153:CTTA:C	donor_loss	1.0000
6:155285154:TTAC:T	donor_loss	1.0000
6:155285155:TACCT:T	donor_loss	1.0000
6:155285156:A:AC	donor_gain	1.0000
6:155285156:AC:A	donor_gain	1.0000
6:155285156:ACCT:A	donor_gain	1.0000
6:155285156:ACCTC:A	donor_loss	1.0000
6:155285157:C:A	donor_loss	1.0000
6:155285157:C:CA	donor_gain	1.0000
6:155285157:CC:C	donor_gain	1.0000
6:155285157:CCT:C	donor_gain	1.0000
6:155285157:CCTC:C	donor_gain	1.0000
6:155285157:CCTCT:C	donor_gain	1.0000
6:155285273:AGTCT:A	acceptor_gain	1.0000
6:155285274:GTCT:G	acceptor_gain	1.0000
6:155285274:GTCTC:G	acceptor_gain	1.0000
6:155285275:TCTC:T	acceptor_gain	1.0000
6:155285276:CT:C	acceptor_gain	1.0000
6:155285276:CTCT:C	acceptor_gain	1.0000

AlphaMissense

2258 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:155285173:A:C	F217L	0.997
6:155285173:A:T	F217L	0.997
6:155285175:A:G	F217L	0.997
6:155297067:A:C	F144L	0.997
6:155297067:A:T	F144L	0.997
6:155297069:A:G	F144L	0.997
6:155314324:C:A	Q35H	0.996
6:155314324:C:G	Q35H	0.996
6:155297039:A:G	W154R	0.995
6:155297039:A:T	W154R	0.995
6:155297076:A:C	N141K	0.994
6:155297076:A:T	N141K	0.994
6:155314318:G:C	F37L	0.994
6:155314318:G:T	F37L	0.994
6:155314320:A:G	F37L	0.994
6:155296968:T:A	Q177H	0.993
6:155296968:T:G	Q177H	0.993
6:155297080:C:T	G140E	0.993
6:155311214:C:G	D87H	0.993
6:155260308:A:C	F253L	0.992
6:155260308:A:T	F253L	0.992
6:155260310:A:G	F253L	0.992
6:155311219:T:A	E85V	0.992
6:155311222:A:T	V84D	0.991
6:155311252:A:G	L74P	0.991
6:155311297:A:T	V59D	0.991
6:155311219:T:G	E85A	0.990
6:155311264:G:T	T70K	0.990
6:155311273:C:T	G67E	0.990
6:155257958:A:C	Y307D	0.989

dbSNP variants (sampled 300 via entrez): RS1000036094 (6:155241015 T>C), RS1000100207 (6:155282787 G>T), RS1000115020 (6:155255116 G>C), RS1000132263 (6:155282358 T>C), RS1000152588 (6:155282901 G>C,T), RS1000191528 (6:155304837 T>C), RS1000210666 (6:155314635 G>A,T), RS1000210798 (6:155232939 C>T), RS1000291402 (6:155256996 A>G,T), RS1000353683 (6:155242382 G>A), RS1000377841 (6:155276812 T>G), RS1000534056 (6:155307034 T>C), RS1000543866 (6:155279065 A>G), RS1000567928 (6:155265084 G>A), RS1000632714 (6:155263517 C>A)

Disease associations

OMIM: gene MIM:607033 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST005756_4	Dimensional psychopathology (Negative)	1.000000e-06
GCST005758_3	Dimensional psychopathology (Arousal)	9.000000e-07
GCST008155_40	Waist-hip ratio	3.000000e-06
GCST008159_56	Waist-to-hip ratio adjusted for BMI	4.000000e-06
GCST009391_102	Metabolite levels	6.000000e-06
GCST010397_32	Gut microbiota (bacterial taxa, rank normal transformation method)	2.000000e-06

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0009096	negative domain measurement
EFO:0009099	arousal domain measurement
EFO:0004343	waist-hip ratio
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0009767	glycine measurement
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression, affects cotreatment	3
bisphenol A	affects cotreatment, affects expression, increases abundance, increases methylation	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
FR900359	increases phosphorylation	1
ginger extract	affects cotreatment, affects expression, increases abundance	1
dicrotophos	decreases expression	1
quercitrin	decreases expression	1
sodium arsenite	decreases expression	1
manganese chloride	increases abundance, increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	decreases expression	1
ICG 001	increases expression	1
teriflunomide	decreases expression	1
NSC 689534	affects binding, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Ethanol	affects cotreatment, decreases expression, increases abundance	1
Arsenic	affects methylation	1
Carbamazepine	affects expression	1
Cisplatin	affects response to substance	1
Copper	affects binding, decreases expression	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	decreases expression	1

Clinical trials (associated diseases)

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