TMEM126B

Chr 11AR

transmembrane protein 126B

Also known as: HT007, MC1DN29

NCBI Gene: 55863ENSG00000171204UniProt: Q8IUX1OMIM: 615533

This mitochondrial transmembrane protein functions as an assembly factor required for formation of the membrane arm of complex I within the MCIA assembly complex. Mutations cause mitochondrial complex I deficiency with autosomal recessive inheritance. The gene shows low constraint to loss-of-function variation, consistent with the recessive disease pattern.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.641 OMIM phenotype
Clinical Summary— TMEM126B
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Gene-Disease Validity (ClinGen)
mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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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
37 unique Pathogenic / Likely Pathogenic· 63 VUS of 161 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.64LOEUF
pLI 0.000
Z-score 0.34
OE 0.86 (0.47–1.64)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.18Z-score
OE missense 1.05 (0.91–1.21)
128 obs / 122.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.86 (0.47–1.64)
0≤0.351.4
Missense OE1.05 (0.91–1.21)
0≤0.61.4
Synonymous OE0.96
0≤1.21.6
LoF obs/exp: 6 / 7.0Missense obs/exp: 128 / 122.4Syn Z: 0.22
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveTMEM126B-related muscle weakness and isolated complex I deficiencyLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7229th %ile
GOF
0.4875th %ile
LOF
0.3549th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

161 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic29
Likely Pathogenic8
VUS63
Likely Benign38
Benign12
Conflicting4
29
Pathogenic
8
Likely Pathogenic
63
VUS
38
Likely Benign
12
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
0
20
0
29
Likely Pathogenic
5
2
1
0
8
VUS
2
51
10
0
63
Likely Benign
0
10
15
13
38
Benign
0
2
10
0
12
Conflicting
—4
Total16655613154

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

View in ClinVar →

Protein Context — Lollipop Plot

TMEM126B · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients