BMERB1

Chr 16

bMERB domain containing 1

Also known as: C16orf45, MINP

NCBI Gene: 89927 ENSG00000166780 UniProt: Q96MC5

The protein is predicted to negatively regulate microtubule depolymerization and control cell motility during cerebral cortex radial glia guided migration within the microtubule cytoskeleton. Mutations in BMERB1 have not been definitively associated with human disease, as this appears to be a predicted gene with limited functional validation. The gene shows relatively low constraint to loss-of-function variants based on population genetics data.

ResearchSummary from RefSeq

Predicted to be involved in negative regulation of microtubule depolymerization. Predicted to act upstream of or within negative regulation of cell motility involved in cerebral cortex radial glia guided migration. Predicted to be active in microtubule cytoskeleton. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.78

Clinical Summary— BMERB1

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 2 VUS of 11 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.78LOEUF

pLI 0.137

Z-score 2.03

OE 0.30 (0.14–0.78)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.41Z-score

OE missense 0.89 (0.76–1.05)

105 obs / 117.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.30 (0.14–0.78)

0≤0.351.4

Missense OE?0.89 (0.76–1.05)

0≤0.61.4

Synonymous OE?1.12

0≤1.21.6

LoF obs/exp: 3 / 9.9Missense obs/exp: 105 / 117.5Syn Z: -0.62

This gene — mechanism propensity

0.73top 25%

GOF

0.7027th %ile

LOF

0.3066th %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

11 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS2

Pathogenic

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	1	1
Likely Pathogenic	0	0	0
VUS	2	0	2
Likely Benign	0	0	0
Benign	0	0	0
Total	2	1	3

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

View in ClinVar →

217 pathogenic / likely-pathogenic (of 365) ClinVar copy-number / structural variants overlap BMERB1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →