TFB2M

protein-coding

transcription factor B2, mitochondrial, the group of 7BS N6-adenosine DNA/RNA methyltransferases

Gene summary

Enables mitochondrial transcription factor activity. Involved in transcription initiation at mitochondrial promoter. Located in mitochondrial nucleoid. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_022366.3

Inheritance

—

ClinVar variants

U:62B:18

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.58

Max pathogenic AF

—

Genomic locus

chr1:246,540,561-246,566,261

External References & Databases

Ensembl (ENSG00000162851)

Transcript & Mutation Effects

hg38 • Region Span ~25.7 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 TFB2M variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 70

not providedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_022366.3. 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				1 clinvar	2 clinvar	3
missense			59 clinvar	15 clinvar		74
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	62	16	2	80

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 37 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_022366.3	RefSeq	NP_071761.1	8	MANE Select
ENST00000366514.5	Ensembl	ENSP00000355471.4	8	MANE Select
ENST00000873621.1	Ensembl	ENSP00000543680.1	6	Standard
ENST00000873621.2	Ensembl	ENSP00000543680.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Energy Metabolism
Mitochondrial biogenesis
Mitochondrial Gene Expression
Gene expression (Transcription)
Transcriptional activation of mitochondrial biogenesis

Biological Process

mitochondrial transcription
transcription initiation from mitochondrial promoter
mitochondrion organization
rRNA methylation
positive regulation of transcription, DNA-templated

Molecular Function

rRNA (adenine-N6,N6-)-dimethyltransferase activity
transcription coregulator activity
RNA binding

Cellular Component

mitochondrion
mitochondrial matrix
mitochondrial nucleoid

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000366514
Coding exons: 8
Length: 25765
Individuals with no LoFs: 125739
Homozygous LoFs: 0
Heterozygous LoFs: 7
Defined: 125746
p: 0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.123	225	220	1.02	0.0000113	2579
Missense (PolyPhen)		57	69.211	0.82357		905
Synonymous	1.05	67	78.9	0.850	0.00000396	752
Loss of Function	1.72	11	19.1	0.576	0.00000106	222

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000026	0.000026	rare
South Asian	0.000065	0.000065	rare
Other	0.00033	0.00033	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. Compared to TFB1M, it activates transcription of mitochondrial DNA more efficiently, while it has less methyltransferase activity. {ECO:0000269|PubMed:12068295, ECO:0000269|PubMed:12897151, ECO:0000269|PubMed:15526033, ECO:0000269|PubMed:20410300}.;

Recessive Scores

pRec: 0.0597

Intolerance Scores

RVIS EVS: -0.14
RVIS percentile EVS: 43.77

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.953

Gene Damage Prediction

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