BORCS8

Summary

BORCS8 (BLOC-1 related complex subunit 8, HGNC:37247) is a protein-coding gene on chromosome 19p13.11, encoding BLOC-1-related complex subunit 8 (Q96FH0). As part of the BLOC-one-related complex (BORC), it plays a role in the movement and localization of lysosomes at the cell periphery.

Involved in heart development. Part of BORC complex.

Source: NCBI Gene 729991 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodegeneration, infantile-onset, with optic atrophy and brain abnormalities (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 7
• Clinical variants (ClinVar): 33 total — 3 pathogenic
• Phenotypes (HPO): 113
• MANE Select transcript: NM_001145784

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:37247
Approved symbol	BORCS8
Name	BLOC-1 related complex subunit 8
Location	19p13.11
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000254901
Ensembl biotype	protein_coding
OMIM	616601
Entrez	729991

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 9 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000462498, ENST00000462790, ENST00000477565, ENST00000488252, ENST00000494489, ENST00000585679, ENST00000588208, ENST00000591398, ENST00000591566, ENST00000892307, ENST00000892308, ENST00000916350, ENST00000963658, ENST00000963659

RefSeq mRNA: 2 — MANE Select: NM_001145784 NM_001145783, NM_001145784

CCDS: CCDS46025, CCDS54235

Canonical transcript exons

ENST00000462790 — 6 exons

Exon	Start	End
ENSE00003540035	19186893	19187005
ENSE00003554949	19186034	19186098
ENSE00003652601	19182573	19182683
ENSE00003688238	19180686	19180761
ENSE00003698664	19176906	19177460
ENSE00003843470	19192081	19192152

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 92.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.6054 / max 128.3385, expressed in 1810 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
180128	22.6054	1810

Top tissues by expression

284 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
prefrontal cortex	UBERON:0000451	92.43	gold quality
anterior cingulate cortex	UBERON:0009835	91.05	gold quality
cingulate cortex	UBERON:0003027	90.95	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.77	gold quality
right frontal lobe	UBERON:0002810	90.34	gold quality
adenohypophysis	UBERON:0002196	90.33	gold quality
apex of heart	UBERON:0002098	90.28	gold quality
blood	UBERON:0000178	89.91	gold quality
granulocyte	CL:0000094	89.75	gold quality
nucleus accumbens	UBERON:0001882	89.61	gold quality
frontal cortex	UBERON:0001870	89.31	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.31	gold quality
neocortex	UBERON:0001950	89.26	gold quality
pituitary gland	UBERON:0000007	89.19	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	89.17	gold quality
putamen	UBERON:0001874	89.01	gold quality
metanephros cortex	UBERON:0010533	89.01	gold quality
amygdala	UBERON:0001876	88.37	gold quality
gastrocnemius	UBERON:0001388	88.33	gold quality
caudate nucleus	UBERON:0001873	88.26	gold quality
right lobe of thyroid gland	UBERON:0001119	88.18	gold quality
mucosa of transverse colon	UBERON:0004991	88.16	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	88.08	gold quality
right atrium auricular region	UBERON:0006631	87.94	gold quality
left lobe of thyroid gland	UBERON:0001120	87.68	gold quality
lower esophagus mucosa	UBERON:0035834	87.66	gold quality
pons	UBERON:0000988	87.58	gold quality
cerebellar vermis	UBERON:0004720	87.46	gold quality
cerebral cortex	UBERON:0000956	87.45	gold quality
hypothalamus	UBERON:0001898	87.36	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.28

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting BORCS8, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-4758-3P	99.12	63.96	869
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-5000-3P	98.79	65.63	1251
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-4733-3P	98.35	65.20	994
HSA-MIR-124-5P	98.11	67.65	1095
HSA-MIR-4436A	98.05	64.83	1140
HSA-MIR-22-5P	97.67	68.92	1355
HSA-MIR-4288	97.11	67.23	1636
HSA-MIR-1913	97.07	66.20	1417
HSA-MIR-346	97.01	66.97	662
HSA-MIR-632	96.08	67.17	798

Literature-anchored findings (GeneRIF, showing 2)

• BORC complex specific components and Kinesin-1 mediate autophagy evasion by the autophagy-resistant Mycobacterium tuberculosis Beijing strain. (PMID:36717601)
• Biallelic BORCS8 variants cause an infantile-onset neurodegenerative disorder with altered lysosome dynamics. (PMID:38128568)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	borcs8	ENSDARG00000071339
mus_musculus	Borcs8	ENSMUSG00000002345
rattus_norvegicus	Borcs8	ENSRNOG00000020427
drosophila_melanogaster	CG32590	FBGN0052590
caenorhabditis_elegans	blos-9	WBGENE00010767

Protein

Protein identifiers

BLOC-1-related complex subunit 8 — Q96FH0 (reviewed: Q96FH0)

Alternative names: MEF2B neighbor

All UniProt accessions (3): Q96FH0, K7ENY0, U3KPZ4

UniProt curated annotations — full annotation on UniProt →

Function. As part of the BLOC-one-related complex (BORC), it plays a role in the movement and localization of lysosomes at the cell periphery. Associated with the cytosolic face of lysosomes, BORC recruits ARL8B to the lysosomal membrane and couples lysosomes to microtubule plus-end-directed kinesin motors, driving lysosome movement toward the cell periphery.

Subunit / interactions. Component of the BLOC-one-related complex (BORC) which is composed of BLOC1S1, BLOC1S2, BORCS5, BORCS6, BORCS7, BORCS8, KXD1 and SNAPIN.

Subcellular location. Lysosome membrane.

Disease relevance. Neurodegeneration, infantile-onset, with optic atrophy and brain abnormalities (NDOABA) [MIM:620987] An autosomal recessive, severe early-infantile disorder characterized by global developmental delay, severe to profound intellectual disability, hypotonia, limb spasticity, muscle wasting, dysmorphic facies, optic atrophy, leuko-axonopathy with hypomyelination, and neurodegenerative features with prevalent supratentorial involvement. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the BORCS8 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96FH0-1	1	yes
Q96FH0-2	2

RefSeq proteins (2): NP_001139255, NP_001139256* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019320	BORCS8	Family

Pfam: PF10167

UniProt features (7 total): sequence variant 3, splice variant 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96FH0-F1	92.74	0.85

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 109

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 340 (showing top): GOCC_VACUOLAR_MEMBRANE, GOBP_ORGANELLE_TRANSPORT_ALONG_MICROTUBULE, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, KOKKINAKIS_METHIONINE_DEPRIVATION_96HR_UP, KOKKINAKIS_METHIONINE_DEPRIVATION_48HR_UP, GOBP_ORGANELLE_LOCALIZATION, EBAUER_MYOGENIC_TARGETS_OF_PAX3_FOXO1_FUSION, GOBP_CIRCULATORY_SYSTEM_DEVELOPMENT, GOCC_CYTOPLASMIC_SIDE_OF_MEMBRANE, GOCC_SIDE_OF_MEMBRANE, chr19p13, KYNG_WERNER_SYNDROM_AND_NORMAL_AGING_DN, GOBP_INTRACELLULAR_TRANSPORT, GOBP_ESTABLISHMENT_OF_ORGANELLE_LOCALIZATION, GOCC_CYTOPLASMIC_SIDE_OF_LYSOSOMAL_MEMBRANE

GO Biological Process (5): heart development (GO:0007507), lysosome localization (GO:0032418), regulation of endosome size (GO:0051036), regulation of lysosome size (GO:0062196), organelle transport along microtubule (GO:0072384)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (5): cytoplasmic side of lysosomal membrane (GO:0098574), BORC complex (GO:0099078), lysosome (GO:0005764), lysosomal membrane (GO:0005765), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
animal organ development	1
circulatory system development	1
vacuolar localization	1
regulation of vesicle size	1
regulation of cellular component size	1
transport along microtubule	1
establishment of organelle localization	1
binding	1
lysosomal membrane	1
cytoplasmic side of membrane	1
intracellular protein-containing complex	1
lytic vacuole	1
lysosome	1
lytic vacuole membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

404 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BORCS8	BORCS5	Q969J3	986
BORCS8	KXD1	Q9BQD3	985
BORCS8	BLOC1S1	P78537	975
BORCS8	BLOC1S2	Q6QNY1	973
BORCS8	BORCS6	Q96GS4	970
BORCS8	BORCS7	Q96B45	968
BORCS8	SNAPIN	O95295	956
BORCS8	ARL8B	Q9NVJ2	632
BORCS8	ARL5B	Q96KC2	622
BORCS8	ARL8A	Q96BM9	565
BORCS8	MEF2B	Q02080	551
BORCS8	LAMTOR4	Q0VGL1	522
BORCS8	RNF157	Q96PX1	479
BORCS8	SFSWAP	Q12872	472
BORCS8	RFXANK	O14593	447

IntAct

34 interactions, top by confidence:

A	B	Type	Score
BORCS8	TEX11	psi-mi:“MI:0915”(physical association)	0.700
TEX11	BORCS8	psi-mi:“MI:0915”(physical association)	0.700
CTAG1A	BORCS8	psi-mi:“MI:0915”(physical association)	0.560
AGR2	BORCS8	psi-mi:“MI:0915”(physical association)	0.560
MESD	BORCS8	psi-mi:“MI:0915”(physical association)	0.560
BORCS6	HSBP1	psi-mi:“MI:0914”(association)	0.530
BORCS8	SNAPIN	psi-mi:“MI:0914”(association)	0.530
BORCS8	P2RX5	psi-mi:“MI:0915”(physical association)	0.490
P2RX5	BORCS8	psi-mi:“MI:0915”(physical association)	0.490
DTNBP1	AP3B1	psi-mi:“MI:0914”(association)	0.350
SHANK3	IGKV3D-15	psi-mi:“MI:0914”(association)	0.350
BORCS8	TP73	psi-mi:“MI:0914”(association)	0.350
LAMTOR5	ERI3	psi-mi:“MI:0914”(association)	0.350
BORCS7	SNAPIN	psi-mi:“MI:0914”(association)	0.350
BORCS8	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
RAB9A	SNAP23	psi-mi:“MI:2364”(proximity)	0.270
BORCS8	CTAG1A	psi-mi:“MI:0915”(physical association)	0.000
BORCS8	TEX11	psi-mi:“MI:0915”(physical association)	0.000
BORCS8	AGR2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (51): MEF2BNB (Two-hybrid), MEF2BNB (Affinity Capture-MS), MEF2BNB (Affinity Capture-MS), MEF2BNB (Affinity Capture-MS), MEF2BNB (Affinity Capture-MS), MEF2BNB (Affinity Capture-MS), TEX11 (Two-hybrid), P2RX5 (Two-hybrid), MEF2BNB (Proximity Label-MS), MEF2BNB (Two-hybrid), MEF2BNB (Two-hybrid), MEF2BNB (Two-hybrid), MEF2BNB (Two-hybrid), CTAG1A (Two-hybrid), KIAA0100 (Affinity Capture-MS)

ESM2 similar proteins: A0A098D1N7, A8E1C4, B4G5J0, C5DGT3, D0UFC9, G0S0N0, O17213, O36307, O36384, O48559, O48767, O62238, P0C6K3, P0CK49, P0CK50, P0CK62, P22225, P28961, P29065, P34665, P55408, P70213, Q00123, Q01048, Q05127, Q18446, Q21738, Q26789, Q29S20, Q2H137, Q30NP5, Q502G5, Q50HP3, Q5XX07, Q66406, Q66639, Q6FTK3, Q6PEB9, Q6UDH8, Q6V1Q9

Diamond homologs: A3KQI3, A7SGF0, O45685, Q4S3C1, Q54JC6, Q8IR45, Q96FH0, Q9D6Y4, Q15075, Q8BL66

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

33 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	29
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
3363149	NM_001145784.2(BORCS8):c.71_75dup (p.Asn26fs)	Pathogenic
3363151	NM_001145784.2(BORCS8):c.196A>C (p.Thr66Pro)	Pathogenic
3363152	NM_001145784.2(BORCS8):c.124T>C (p.Ser42Pro)	Pathogenic

SpliceAI

1376 predictions. Top by Δscore:

Variant	Effect	Δscore
19:19182615:ATGG:A	donor_gain	1.0000
19:19182679:CGGCG:C	acceptor_gain	1.0000
19:19182680:GGCG:G	acceptor_gain	1.0000
19:19182681:GCG:G	acceptor_gain	1.0000
19:19182682:CG:C	acceptor_gain	1.0000
19:19182682:CGC:C	acceptor_gain	1.0000
19:19182684:C:CC	acceptor_gain	1.0000
19:19186888:CTCAC:C	donor_loss	1.0000
19:19186889:TCA:T	donor_loss	1.0000
19:19186890:CA:C	donor_loss	1.0000
19:19186892:C:CT	donor_loss	1.0000
19:19187004:GA:G	acceptor_gain	1.0000
19:19187004:GAC:G	acceptor_loss	1.0000
19:19187005:ACTAG:A	acceptor_loss	1.0000
19:19187006:C:CA	acceptor_loss	1.0000
19:19187006:C:CC	acceptor_gain	1.0000
19:19187007:T:C	acceptor_loss	1.0000
19:19187034:G:C	acceptor_gain	1.0000
19:19192087:T:TA	donor_gain	1.0000
19:19192088:C:A	donor_gain	1.0000
19:19192503:ATAAG:A	donor_gain	1.0000
19:19182455:C:CT	acceptor_gain	0.9900
19:19182568:GCTA:G	donor_loss	0.9900
19:19182568:GCTAC:G	donor_loss	0.9900
19:19182569:CTA:C	donor_loss	0.9900
19:19182570:TA:T	donor_loss	0.9900
19:19182571:A:C	donor_loss	0.9900
19:19182572:C:CT	donor_loss	0.9900
19:19182572:C:T	donor_loss	0.9900
19:19182599:ATGGT:A	donor_gain	0.9900

AlphaMissense

783 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:19186041:C:G	A70P	0.999
19:19186906:A:G	L46P	0.999
19:19186921:C:G	R41P	0.999
19:19186924:C:G	R40P	0.999
19:19186927:A:T	V39E	0.999
19:19186929:A:C	H38Q	0.999
19:19186929:A:T	H38Q	0.999
19:19186930:T:C	H38R	0.999
19:19186930:T:G	H38P	0.999
19:19186931:G:C	H38D	0.999
19:19186939:A:G	L35P	0.999
19:19186942:C:G	R34P	0.999
19:19186951:G:T	A31D	0.999
19:19186957:G:A	S29F	0.999
19:19186957:G:T	S29Y	0.999
19:19186960:G:T	P28Q	0.999
19:19186963:T:A	E27V	0.999
19:19186963:T:C	E27G	0.999
19:19182619:C:G	A94P	0.998
19:19182682:C:G	A73P	0.998
19:19186065:C:G	G62R	0.998
19:19186065:C:T	G62R	0.998
19:19186069:G:C	S60R	0.998
19:19186069:G:T	S60R	0.998
19:19186071:T:G	S60R	0.998
19:19186915:A:G	L43P	0.998
19:19186919:A:G	S42P	0.998
19:19186922:G:T	R41S	0.998
19:19186931:G:T	H38N	0.998
19:19186934:C:T	E37K	0.998

dbSNP variants (sampled 300 via entrez): RS1000011633 (19:19187199 G>A,T), RS1000049634 (19:19181313 A>G), RS1000100115 (19:19181639 G>A), RS1000308407 (19:19176588 C>A,T), RS1000362990 (19:19186955 C>A,T), RS1000416942 (19:19190486 C>T), RS1000472114 (19:19179031 G>A), RS1000482919 (19:19189917 A>C), RS1001177589 (19:19187545 T>C), RS1001419072 (19:19186006 CCTG>C), RS1001476162 (19:19189021 G>A,C), RS1001574719 (19:19189730 A>G), RS1001622978 (19:19178602 A>C), RS1001768113 (19:19184622 C>T), RS1001925712 (19:19178805 C>A)

Disease associations

OMIM: gene MIM:616601 | disease phenotypes: MIM:620987

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodegeneration, infantile-onset, with optic atrophy and brain abnormalities	Strong	Autosomal recessive
inherited neurodegenerative disorder	Limited	Autosomal recessive

Mondo (2): neurodegeneration, infantile-onset, with optic atrophy and brain abnormalities (MONDO:0975837), inherited neurodegenerative disorder (MONDO:0024237)

Orphanet (0):

HPO phenotypes

113 total (30 of 113 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000020	Urinary incontinence
HP:0000179	Thick lower lip vermilion
HP:0000215	Thick upper lip vermilion
HP:0000252	Microcephaly
HP:0000275	Narrow face
HP:0000276	Long face
HP:0000280	Coarse facial features
HP:0000286	Epicanthus
HP:0000297	Facial hypotonia
HP:0000316	Hypertelorism
HP:0000336	Prominent supraorbital ridges
HP:0000341	Narrow forehead
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000389	Chronic otitis media
HP:0000400	Macrotia
HP:0000414	Bulbous nose
HP:0000426	Prominent nasal bridge
HP:0000454	Flared nostrils
HP:0000455	Broad nasal tip
HP:0000463	Anteverted nares
HP:0000490	Deeply set eye
HP:0000494	Downslanted palpebral fissures
HP:0000527	Long eyelashes
HP:0000543	Optic disc pallor
HP:0000574	Thick eyebrow
HP:0000582	Upslanted palpebral fissure
HP:0000648	Optic atrophy
HP:0000664	Synophrys

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST003434_1	Obsessive-compulsive symptoms	3.000000e-08
GCST007706_37	Mean arterial pressure	6.000000e-08
GCST007706_76	Mean arterial pressure	9.000000e-08
GCST008103_10	Bipolar disorder	1.000000e-09
GCST008115_2	Bipolar I disorder	3.000000e-09
GCST008116_4	Bipolar II disorder	4.000000e-06
GCST008163_12	Height	4.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007802	obsessive-compulsive symptom measurement
EFO:0006340	mean arterial pressure
EFO:0009963	bipolar I disorder
EFO:0009964	bipolar II disorder

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D020271	Heredodegenerative Disorders, Nervous System	C10.574.500; C16.320.400

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	7
belinostat	increases expression, affects cotreatment	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
afuresertib	decreases expression	1
sotorasib	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases reaction, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	increases expression, affects cotreatment	1
trametinib	affects cotreatment, increases expression	1
NVP-BKM120	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Vorinostat	increases expression	1
Vehicle Emissions	decreases reaction, increases expression	1
Caffeine	increases phosphorylation	1
Cisplatin	affects cotreatment, increases expression	1
Silicon Dioxide	increases expression	1
Smoke	decreases expression	1
Acrylamide	decreases expression	1
Particulate Matter	decreases reaction, increases expression	1

Clinical trials (associated diseases)

1 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01498263	Not specified	COMPLETED	Inherited Diseases, Caregiving, and Social Networks