TFB2M

Chr 1

transcription factor B2, mitochondrial

Also known as: Hkp1, h-mtTFB, h-mtTFB2, hTFB2M, mtTFB2

NCBI Gene: 64216ENSG00000162851UniProt: Q9H5Q4

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

181
ClinVar variants
76
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TFB2M
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
76 Pathogenic / Likely Pathogenic· 82 VUS of 181 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.
0.95LOEUF
pLI 0.000
Z-score 1.72
OE 0.58 (0.36–0.95)
Tolerant

Typical tolerance to LoF variation

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.
-0.12Z-score
OE missense 1.02 (0.92–1.14)
225 obs / 219.9 exp
Tolerant

Tolerant to missense variation

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.0.58 (0.36–0.95)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.02 (0.92–1.14)
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.0.85
0≤1.21.6
LoF obs/exp: 11 / 19.1Missense obs/exp: 225 / 219.9Syn Z: 1.05

ClinVar Variant Classifications

181 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic69
Likely Pathogenic7
VUS82
Likely Benign21
Benign2
69
Pathogenic
7
Likely Pathogenic
82
VUS
21
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
69
0
69
Likely Pathogenic
0
0
7
0
7
VUS
0
57
25
0
82
Likely Benign
0
14
6
1
21
Benign
0
0
0
2
2
Total0711073181

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

View in ClinVar →

Protein Context — Lollipop Plot

TFB2M · 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
Over-expression of TFB2M facilitates cell growth and metastasis via activating ROS-Akt-NF-κB signalling in hepatocellular carcinoma.
Geng X et al.·Liver Int
2020
Mitochondrial DNA depletion and its correlation with TFAM, TFB1M, TFB2M and POLG in human diffusely infiltrating astrocytomas.
Correia RL et al.·Mitochondrion
2011
Identification of a rare homozygous c.790C>T variation in the TFB2M gene in Korean patients with autism spectrum disorder.
Park CB et al.·Biochem Biophys Res Commun
2018Cohort
Transcribing β-cell mitochondria in health and disease.
Mulder H·Mol Metab
2017Review
Mitochondrial GWAS and association of nuclear - mitochondrial epistasis with BMI in T1DM patients.
Ludwig-Słomczyńska AH et al.·BMC Med Genomics
2020Cohort
The protein interaction of mitochondrial transcription factors A and B2 is associated with 30-day survival in critical COVID-19.
Westhus B et al.·Front Immunol
2025
Poly(ADP-ribose) polymerase-1 is a nuclear epigenetic regulator of mitochondrial DNA repair and transcription.
Lapucci A et al.·Mol Pharmacol
2011
Dysregulation of mitochondrial dynamics and the muscle transcriptome in ICU patients suffering from sepsis induced multiple organ failure.
Fredriksson K et al.·PLoS One
2008Cohort
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