BORCS6

Chr 17

BLOC-1 related complex subunit 6

Also known as: C17orf59, PRO2472

BORCS6 encodes a component of the BORC complex that regulates lysosome movement and localization at the cell periphery by recruiting motor proteins to lysosomes. Mutations cause autosomal recessive developmental delays, seizures, and neurodegeneration with onset in infancy or early childhood. The gene shows moderate tolerance to loss-of-function variants, consistent with recessive inheritance requiring biallelic mutations for disease manifestation.

OMIMResearchSummary from RefSeq, UniProt
GOFmechanismLOEUF 0.92
Clinical SummaryBORCS6
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.92LOEUF
pLI 0.201
Z-score 1.71
OE 0.29 (0.120.92)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.90Z-score
OE missense 0.82 (0.730.94)
172 obs / 208.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.29 (0.120.92)
00.351.4
Missense OE0.82 (0.730.94)
00.61.4
Synonymous OE0.89
01.21.6
LoF obs/exp: 2 / 6.8Missense obs/exp: 172 / 208.7Syn Z: 0.88
DN
0.4685th %ile
GOF
0.7027th %ile
LOF
0.49top 25%

The highest-scoring mechanism for this gene is gain-of-function.

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

BORCS6 · 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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