TFB1M

Chr 6

transcription factor B1, mitochondrial

Also known as: CGI-75, CGI75, mtTFB, mtTFB1

NCBI Gene: 51106 ENSG00000029639 UniProt: Q8WVM0 OMIM: 607033

The protein functions as a mitochondrial dimethyltransferase that methylates conserved adenosine residues in 12S rRNA and is required for basal transcription of mitochondrial DNA. Mutations cause combined oxidative phosphorylation deficiency 18, which presents as a mitochondrial disorder with variable features including encephalomyopathy, developmental delay, and hearing loss. The gene follows autosomal recessive inheritance and is extremely intolerant to loss-of-function variants.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.40

Clinical Summary— TFB1M

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

162 VUS of 206 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.40LOEUF

pLI 0.000

Z-score 0.34

OE 0.91 (0.61–1.40)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.15Z-score

OE missense 0.97 (0.86–1.10)

181 obs / 186.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.91 (0.61–1.40)

0≤0.351.4

Missense OE?0.97 (0.86–1.10)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 15 / 16.5Missense obs/exp: 181 / 186.8Syn Z: 0.12

This gene — mechanism propensity

0.6648th %ile

GOF

0.4677th %ile

LOF

0.3649th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

206 submitted variants in ClinVar

ClinVar

Classification Summary

VUS162

Likely Benign9

Benign5

162

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	162	0	0	162
Likely Benign	8	1	0	9
Benign	2	1	2	5
Total	172	2	2	176

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

28 pathogenic / likely-pathogenic (of 33) ClinVar copy-number / structural variants overlap TFB1M — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →