MINAR2

Chr 5AR

membrane integral NOTCH2 associated receptor 2

Also known as: DFNB120, KIAA1024L

NCBI Gene: 100127206 ENSG00000186367 UniProt: P59773 OMIM: 620215

This protein binds cholesterol and regulates cholesterol distribution and homeostasis in hair cells, and may function in angiogenesis. Mutations cause autosomal recessive nonsyndromic deafness (DFNB120). The gene is not highly constrained against loss-of-function variants, consistent with its autosomal recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Enables cholesterol binding activity. Involved in angiogenesis. Located in endoplasmic reticulum. Implicated in autosomal recessive nonsyndromic deafness. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 1.481 OMIM phenotype

Clinical Summary— MINAR2

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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?

1.48LOEUF

pLI 0.001

Z-score 0.69

OE 0.72 (0.37–1.48)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.67Z-score

OE missense 0.79 (0.65–0.97)

67 obs / 84.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.72 (0.37–1.48)

0≤0.351.4

Missense OE?0.79 (0.65–0.97)

0≤0.61.4

Synonymous OE?0.74

0≤1.21.6

LoF obs/exp: 5 / 7.0Missense obs/exp: 67 / 84.4Syn Z: 1.14

This gene — mechanism propensity

0.83top 10%

GOF

0.82top 10%

LOF

0.3068th %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.