MLANA

Chr 9

melan-A

Also known as: MART-1, MART1

The protein is involved in melanosome biogenesis by stabilizing GPR143 and ensuring proper expression, stability, trafficking, and processing of PMEL, which is critical for stage II melanosome formation. Mutations cause autosomal recessive ocular albinism with late-onset deafness, affecting pigmentation and hearing systems. The gene shows low constraint against loss-of-function variants.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.95
Clinical SummaryMLANA
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.95LOEUF
pLI 0.000
Z-score -1.65
OE 1.70 (0.991.95)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.12Z-score
OE missense 1.04 (0.851.28)
67 obs / 64.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.70 (0.991.95)
00.351.4
Missense OE1.04 (0.851.28)
00.61.4
Synonymous OE1.13
01.21.6
LoF obs/exp: 11 / 6.5Missense obs/exp: 67 / 64.3Syn Z: -0.52
DN
0.6842th %ile
GOF
0.6345th %ile
LOF
0.3844th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction 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

MLANA · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
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