TFB1M

Chr 6

transcription factor B1, mitochondrial

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

NCBI Gene: 51106ENSG00000029639UniProt: Q8WVM0

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]

208
ClinVar variants
28
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TFB1M
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
28 Pathogenic / Likely Pathogenic· 166 VUS of 208 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.15Z-score
OE missense 0.97 (0.86–1.10)
181 obs / 186.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.91 (0.61–1.40)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.97 (0.86–1.10)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.98
0≤1.21.6
LoF obs/exp: 15 / 16.5Missense obs/exp: 181 / 186.8Syn Z: 0.12

ClinVar Variant Classifications

208 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic26
Likely Pathogenic2
VUS166
Likely Benign9
Benign5
26
Pathogenic
2
Likely Pathogenic
166
VUS
9
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
26
0
26
Likely Pathogenic
0
0
2
0
2
VUS
0
161
5
0
166
Likely Benign
0
8
1
0
9
Benign
0
2
1
2
5
Total0171352208

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

View in ClinVar →

Protein Context — Lollipop Plot

TFB1M · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Autophagy deficiency abolishes liver mitochondrial DNA segregation.
Tostes K et al.·Autophagy
2022
A common variant in TFB1M is associated with reduced insulin secretion and increased future risk of type 2 diabetes.
Koeck T et al.·Cell Metab
2011
Genetic variants affecting mitochondrial function provide further insights for kidney disease.
Cañadas-Garre M et al.·BMC Genomics
2024
Mitochondrial DNA depletion and its correlation with TFAM, TFB1M, TFB2M and POLG in human diffusely infiltrating astrocytomas.
Correia RL et al.·Mitochondrion
2011
Loss of TFB1M results in mitochondrial dysfunction that leads to impaired insulin secretion and diabetes.
Sharoyko VV et al.·Hum Mol Genet
2014
Transcribing β-cell mitochondria in health and disease.
Mulder H·Mol Metab
2017Review
Bioinformatics analysis of comorbid mechanisms between ischemic stroke and end stage renal disease.
Wang S et al.·Sci Rep
2025Functional
Nuclear factors: roles related to mitochondrial deafness.
Luo LF et al.·Gene
2013Review
Mitochondrial m.1584A 12S m62A rRNA methylation in families with m.1555A>G associated hearing loss.
O'Sullivan M et al.·Hum Mol Genet
2015
Human mitochondrial transcription factor B1 as a modifier gene for hearing loss associated with the mitochondrial A1555G mutation.
Bykhovskaya Y et al.·Mol Genet Metab
2004
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools