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GeneE
5 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
BORCS8
BLOC-1 related complex subunit 8
Chromosome 19 Β· 19p13.11
NCBI Gene: 729991Ensembl: ENSG00000254901.9HGNC: HGNC:37247UniProt: Q96FH0
26PubMed Papers
19Diseases
0Drugs
3Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingBORC complexheart developmentregulation of lysosome sizeneurodegeneration, infantile-onset, with optic atrophy and brain abnormalitiesImmunodeficiency by defective expression of HLA class 2MHC class II deficiencytooth disease
✦AI Summary

BORCS8 is a core component of the BLOC-one-related complex (BORC), a multiprotein complex essential for lysosomal positioning and anterograde transport. As part of BORC, BORCS8 associates with the cytosolic face of lysosomes, where it recruits the small GTPase ARL8 and kinesin-1/-3 microtubule motors to promote lysosome movement toward the cell periphery in non-neuronal cells and the distal axon in neurons 1. This lysosomal redistribution is critical for neuronal development and function. Biallelic BORCS8 variants cause severe early-infantile neurodegenerative disorder characterized by global developmental delay, profound intellectual disability, hypotonia, limb spasticity, optic atrophy, leuko-axonopathy with hypomyelination, and supratentorial neurodegeneration 1. Pathogenic variants exhibit either reduced assembly with other BORC subunits or complete loss of BORC incorporation, resulting in impaired lysosome distribution to the cell periphery 1. Zebrafish studies confirm that borcs8 knockout recapitulates key disease features including decreased brain and eye size and neuromuscular anomalies 1. These findings establish BORCS8 deficiency as a distinct genetic cause of infantile-onset neurodegeneration and highlight the critical importance of BORC-mediated lysosome dynamics for central nervous system development and function 1.

Sources cited
1
BORCS8 function in BORC complex recruiting ARL8 and kinesin motors for lysosome anterograde transport; biallelic variants cause infantile neurodegenerative disorder with optic atrophy and leuko-axonopathy; variant functional characterization showing impaired BORC assembly and lysosome distribution
PMID: 38128568
⚠Limited data available β€” This gene has 1 indexed publication. Summary and analysis may be incomplete.
Disease Associationsβ“˜19
neurodegeneration, infantile-onset, with optic atrophy and brain abnormalitiesOpen Targets
0.63Moderate
Immunodeficiency by defective expression of HLA class 2Open Targets
0.15Weak
MHC class II deficiencyOpen Targets
0.15Weak
tooth diseaseOpen Targets
0.04Suggestive
esophageal varicesOpen Targets
0.02Suggestive
osteosarcomaOpen Targets
0.01Suggestive
neurodegenerative diseaseOpen Targets
0.01Suggestive
cerebral creatine deficiency syndromeOpen Targets
0.01Suggestive
cancerOpen Targets
0.00Suggestive
meningococcal infectionOpen Targets
0.00Suggestive
obesityOpen Targets
0.00Suggestive
astrocytomaOpen Targets
0.00Suggestive
Cerebral atrophyOpen Targets
0.00Suggestive
COVID-19Open Targets
0.00Suggestive
disease arising from reactivation of latent virusOpen Targets
0.00Suggestive
meningiomaOpen Targets
0.00Suggestive
mycosis fungoidesOpen Targets
0.00Suggestive
Neurodevelopmental disorderOpen Targets
0.00Suggestive
Neurodegeneration, infantile-onset, with optic atrophy and brain abnormalitiesUniProt
Pathogenic Variants3
NM_001145784.2(BORCS8):c.71_75dup (p.Asn26fs)Pathogenic
Neurodegeneration, infantile-onset, with optic atrophy and brain abnormalities
β˜†β˜†β˜†β˜†2024β†’ Residue 26
NM_001145784.2(BORCS8):c.196A>C (p.Thr66Pro)Pathogenic
Neurodegeneration, infantile-onset, with optic atrophy and brain abnormalities
β˜†β˜†β˜†β˜†2024β†’ Residue 66
NM_001145784.2(BORCS8):c.124T>C (p.Ser42Pro)Pathogenic
Neurodegeneration, infantile-onset, with optic atrophy and brain abnormalities
β˜†β˜†β˜†β˜†2024β†’ Residue 42
View on ClinVar β†—
Related Genes
BORCS6Protein interaction92%BORCS5Protein interaction92%BORCS7Protein interaction92%KXD1Protein interaction87%BLOC1S1Protein interaction75%SNAPINProtein interaction71%
Tissue Expression6 tissues
Lung
100%
Liver
90%
Heart
75%
Ovary
68%
Brain
48%
Bone Marrow
44%
Gene Interaction Network
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BORCS8BORCS6BORCS5BORCS7KXD1BLOC1S1SNAPIN
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q96FH0
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.10LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.69 [0.45–1.10]
RankingsWhere BORCS8 stands among ~20K protein-coding genes
  • #12,743of 20,598
    Most Researched26
  • #4,134of 5,498
    Most Pathogenic Variants3
  • #11,295of 17,882
    Most Constrained (LOEUF)1.10
Genes detectedBORCS8
Sources retrieved5 papers
Response timeβ€”
πŸ“„ Sources
5
1
Biallelic BORCS8 variants cause an infantile-onset neurodegenerative disorder with altered lysosome dynamics.
PMID: 38128568
Brain Β· 2024
1.00
2
PMID: 40791729
medRxiv Β· 2025
0.80
3
Effects of
PMID: 33362776
Front Immunol Β· 2020
0.60
4
A Further Case Supporting BORCS8 as a Cause of an Infantile-Onset Neurodegenerative Disorder.
PMID: 40993886
Clin Genet Β· 2026
0.40
5
BLOC1S1 variants cause lysosomal and autophagic defects resulting in a hypomyelinating leukodystrophy with epileptic encephalopathy.
PMID: 41887224
Am J Hum Genet Β· 2026
0.20