TFB1M

protein-coding

transcription factor B1, mitochondrial, the group of 7BS N6-adenosine DNA/RNA methyltransferases

Gene summary

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).[provided by RefSeq, Aug 2010]

MANE transcript

NM_016020.4

Inheritance

—

ClinVar variants

U:56B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.91

Max pathogenic AF

—

Genomic locus

chr6:155,256,134-155,314,493

External References & Databases

Ensembl (ENSG00000029639)

Transcript & Mutation Effects

hg38 • Region Span ~58.4 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 TFB1M variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 82

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016020.4. 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			2 clinvar		1 clinvar	3
missense			50 clinvar	5 clinvar		55
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	56	5	1	62

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 59 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016020.4	RefSeq	NP_057104.2	7	MANE Select
ENST00000367166.5	Ensembl	ENSP00000356134.4	7	MANE Select
NM_001350501.2	RefSeq	NP_001337430.1	7	Standard
NM_001350502.2	RefSeq	NP_001337431.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Energy Metabolism
Mitochondrial biogenesis
Mitochondrial Gene Expression
rRNA processing
rRNA modification in the mitochondrion

Biological Process

rRNA modification
mitochondrion organization
rRNA methylation

Molecular Function

rRNA (adenine-N6,N6-)-dimethyltransferase activity
DNA binding
RNA binding
protein binding

Cellular Component

mitochondrial matrix
mitochondrial nucleoid

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000367166
Coding exons: 7
Length: 56985
Individuals with no LoFs: 125641
Homozygous LoFs: 0
Heterozygous LoFs: 107
Defined: 125748
p: 0.000426

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.150	181	187	0.969	0.0000102	2246
Missense (PolyPhen)		76	77.083	0.98594		949
Synonymous	0.115	68	69.2	0.982	0.00000377	684
Loss of Function	0.338	15	16.5	0.910	0.00000100	172

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00049	0.00049	rare
Latino/Admixed American	0.00038	0.00038	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00038	0.00038	rare
Finnish	0.00033	0.00032	rare
European (Non-Finnish)	0.00054	0.00054	rare
South Asian	0.00026	0.00026	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: S-adenosyl-L-methionine-dependent methyltransferase which specifically dimethylates mitochondrial 12S rRNA at the conserved stem loop. Also required for basal transcription of mitochondrial DNA, probably via its interaction with POLRMT and TFAM. Stimulates transcription independently of the methyltransferase activity. {ECO:0000269|PubMed:11809803, ECO:0000269|PubMed:12068295, ECO:0000269|PubMed:12897151}.;
Disease: DISEASE: Note=Variations in TFB1M may influence the clinical expression of aminoglycoside-induced deafness caused by the A1555G mutation in the mitochondrial 12S rRNA.;

Recessive Scores

pRec: 0.103

Intolerance Scores

LoFtool: 0.903
RVIS EVS: 0.26
RVIS percentile EVS: 70.44

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.571

Gene Damage Prediction

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