TFB2M

Chr 1

transcription factor B2, mitochondrial

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

TFB2M encodes a mitochondrial rRNA methyltransferase that is an essential component of the mitochondrial transcription initiation complex, required for transcription of mitochondrial DNA. Mutations cause combined oxidative phosphorylation deficiency, an autosomal recessive mitochondrial disorder presenting with early-onset encephalomyopathy, developmental delay, and respiratory chain dysfunction. The gene shows high evolutionary constraint, reflecting its critical role in mitochondrial function.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.95
Clinical SummaryTFB2M
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.95LOEUF
pLI 0.000
Z-score 1.72
OE 0.58 (0.360.95)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.12Z-score
OE missense 1.02 (0.921.14)
225 obs / 219.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.58 (0.360.95)
00.351.4
Missense OE1.02 (0.921.14)
00.61.4
Synonymous OE0.85
01.21.6
LoF obs/exp: 11 / 19.1Missense obs/exp: 225 / 219.9Syn Z: 1.05
DN
0.74top 25%
GOF
0.5170th %ile
LOF
0.2288th %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

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →