TMEM186

Chr 16

transmembrane protein 186

Also known as: C16orf51

NCBI Gene: 25880 ENSG00000184857 UniProt: Q96B77 OMIM: 620433

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.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a potential transmembrane protein. [provided by RefSeq, Dec 2012]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.58

Clinical Summary— TMEM186

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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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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.58LOEUF

pLI 0.000

Z-score 0.38

OE 0.86 (0.49–1.58)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.25Z-score

OE missense 1.31 (1.16–1.49)

168 obs / 128.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.86 (0.49–1.58)

0≤0.351.4

Missense OE?1.31 (1.16–1.49)

0≤0.61.4

Synonymous OE?1.29

0≤1.21.6

LoF obs/exp: 7 / 8.2Missense obs/exp: 168 / 128.1Syn Z: -1.56

This gene — mechanism propensity

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.