TFB2M

Chr 1

transcription factor B2, mitochondrial

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

NCBI Gene: 64216 ENSG00000162851 UniProt: Q9H5Q4 OMIM: 607055

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.

OMIM ResearchSummary from RefSeq, UniProt

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

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.95

Clinical Summary— TFB2M

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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

58 VUS of 95 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?

0.95LOEUF

pLI 0.000

Z-score 1.72

OE 0.58 (0.36–0.95)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.12Z-score

OE missense 1.02 (0.92–1.14)

225 obs / 219.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.58 (0.36–0.95)

0≤0.351.4

Missense OE?1.02 (0.92–1.14)

0≤0.61.4

Synonymous OE?0.85

0≤1.21.6

LoF obs/exp: 11 / 19.1Missense obs/exp: 225 / 219.9Syn Z: 1.05

This gene — mechanism propensity

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

95 submitted variants in ClinVar

ClinVar

Classification Summary

VUS58

Likely Benign16

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	1	57	0	58
Likely Benign	0	15	1	16
Benign	0	0	2	2
Total	1	72	3	76

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

View in ClinVar →

76 pathogenic / likely-pathogenic (of 107) ClinVar copy-number / structural variants overlap TFB2M — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →