BORCS6

Chr 17

BLOC-1 related complex subunit 6

Also known as: C17orf59, PRO2472

NCBI Gene: 54785 ENSG00000196544 UniProt: Q96GS4 OMIM: 616599

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.

OMIM ResearchSummary from RefSeq, UniProt

Enables identical protein binding activity. Involved in lysosome localization. Part of BORC complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

GOFmechanismLOEUF 0.92

Clinical Summary— BORCS6

⚡

Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.

📋

ClinVar Variants

49 VUS of 52 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.92LOEUF

pLI 0.201

Z-score 1.71

OE 0.29 (0.12–0.92)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.90Z-score

OE missense 0.82 (0.73–0.94)

172 obs / 208.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.29 (0.12–0.92)

0≤0.351.4

Missense OE?0.82 (0.73–0.94)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 2 / 6.8Missense obs/exp: 172 / 208.7Syn Z: 0.88

This gene — mechanism propensity

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

52 submitted variants in ClinVar

ClinVar

Classification Summary

VUS49

Likely Benign3

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	49	49
Likely Benign	3	3
Benign	0	0
Total	52	52

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

View in ClinVar →

19 pathogenic / likely-pathogenic (of 31) ClinVar copy-number / structural variants overlap BORCS6 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →