TMEM186

Chr 16

transmembrane protein 186

Also known as: C16orf51

The protein functions as part of the MCIA complex and is required for efficient assembly of mitochondrial complex I. Mutations cause mitochondrial complex I deficiency, which typically presents with multisystem involvement including neurological, cardiac, and metabolic manifestations. The condition follows autosomal recessive inheritance.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.58
Clinical SummaryTMEM186
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
1.58LOEUF
pLI 0.000
Z-score 0.38
OE 0.86 (0.491.58)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.25Z-score
OE missense 1.31 (1.161.49)
168 obs / 128.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.86 (0.491.58)
00.351.4
Missense OE1.31 (1.161.49)
00.61.4
Synonymous OE1.29
01.21.6
LoF obs/exp: 7 / 8.2Missense obs/exp: 168 / 128.1Syn Z: -1.56
DN
0.74top 25%
GOF
0.5465th %ile
LOF
0.2581th %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

TMEM186 · 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.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found