BORCS6

Summary

BORCS6 (BLOC-1 related complex subunit 6, HGNC:25939) is a protein-coding gene on chromosome 17p13.1, encoding BLOC-1-related complex subunit 6 (Q96GS4). As part of the BORC complex may play a role in lysosomes movement and localization at the cell periphery.

Enables identical protein binding activity. Involved in lysosome localization. Part of BORC complex.

Source: NCBI Gene 54785 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 53 total — 1 likely-pathogenic
• MANE Select transcript: NM_017622

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25939
Approved symbol	BORCS6
Name	BLOC-1 related complex subunit 6
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20014
Ensembl gene	ENSG00000196544
Ensembl biotype	protein_coding
OMIM	616599
Entrez	54785

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000389017

RefSeq mRNA: 1 — MANE Select: NM_017622 NM_017622

CCDS: CCDS11133

Canonical transcript exons

ENST00000389017 — 1 exons

Exon	Start	End
ENSE00001504684	8188345	8190180

Expression profiles

Bgee: expression breadth ubiquitous, 219 present calls, max score 93.40.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.5502 / max 44.6244, expressed in 1686 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
164416	3.6703	1594
164415	0.5256	265
164414	0.3543	151

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
type B pancreatic cell	CL:0000169	93.40	gold quality
olfactory bulb	UBERON:0002264	90.97	gold quality
granulocyte	CL:0000094	88.65	gold quality
apex of heart	UBERON:0002098	88.29	gold quality
gastrocnemius	UBERON:0001388	85.50	gold quality
mucosa of transverse colon	UBERON:0004991	85.33	gold quality
tongue squamous epithelium	UBERON:0006919	85.01	gold quality
gluteal muscle	UBERON:0002000	84.82	gold quality
vena cava	UBERON:0004087	84.76	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	84.59	gold quality
muscle of leg	UBERON:0001383	84.20	gold quality
blood	UBERON:0000178	84.11	gold quality
lower esophagus mucosa	UBERON:0035834	84.07	gold quality
leukocyte	CL:0000738	83.96	gold quality
cervix squamous epithelium	UBERON:0006922	83.89	gold quality
hindlimb stylopod muscle	UBERON:0004252	83.73	gold quality
monocyte	CL:0000576	83.72	gold quality
mononuclear cell	CL:0000842	83.66	gold quality
muscle organ	UBERON:0001630	82.60	gold quality
right adrenal gland cortex	UBERON:0035827	82.48	gold quality
body of pancreas	UBERON:0001150	82.25	gold quality
skin of leg	UBERON:0001511	82.23	gold quality
right adrenal gland	UBERON:0001233	82.06	gold quality
heart left ventricle	UBERON:0002084	81.81	gold quality
spleen	UBERON:0002106	81.75	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.67	gold quality
cerebellar vermis	UBERON:0004720	81.62	silver quality
cardiac ventricle	UBERON:0002082	81.56	gold quality
esophagus mucosa	UBERON:0002469	81.22	gold quality
right atrium auricular region	UBERON:0006631	81.15	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

33 targeting BORCS6, 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-3692-3P	99.98	70.27	2139
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-4324	99.04	70.14	1569
HSA-MIR-3926	98.95	69.26	1438
HSA-MIR-7113-3P	98.75	65.71	1120
HSA-MIR-548S	98.50	67.17	1213
HSA-MIR-4733-3P	98.35	65.20	994
HSA-MIR-4436B-3P	98.25	65.26	1494
HSA-MIR-6826-3P	98.19	66.32	1153
HSA-MIR-6732-3P	98.17	67.52	802
HSA-MIR-1301-5P	98.09	66.62	495

Literature-anchored findings (GeneRIF, showing 1)

• BORC complex specific components and Kinesin-1 mediate autophagy evasion by the autophagy-resistant Mycobacterium tuberculosis Beijing strain. (PMID:36717601)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	borcs6	ENSDARG00000061023
mus_musculus	Borcs6	ENSMUSG00000045176
rattus_norvegicus	Borcs6	ENSRNOG00000006513
drosophila_melanogaster	BORCS6	FBGN0035140
caenorhabditis_elegans		WBGENE00021376

Protein

Protein identifiers

BLOC-1-related complex subunit 6 — Q96GS4 (reviewed: Q96GS4)

Alternative names: Lysosome-dispersing protein

All UniProt accessions (1): Q96GS4

UniProt curated annotations — full annotation on UniProt →

Function. As part of the BORC complex may play a role in lysosomes movement and localization at the cell periphery. Associated with the cytosolic face of lysosomes, the BORC complex may recruit ARL8B and couple lysosomes to microtubule plus-end-directed kinesin motor.

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.

Similarity. Belongs to the BORCS6 family.

RefSeq proteins (1): NP_060092* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019314	BORCS6	Family
IPR046465	BORCS6_C	Domain

Pfam: PF10157

UniProt features (12 total): compositionally biased region 4, modified residue 3, region of interest 2, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96GS4-F1	66.53	0.34

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 (3): 168, 196, 199

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 101 (showing top): MYAATNNNNNNNGGC_UNKNOWN, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOCC_VACUOLAR_MEMBRANE, GOBP_ORGANELLE_TRANSPORT_ALONG_MICROTUBULE, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, RYTTCCTG_ETS2_B, KIM_GASTRIC_CANCER_CHEMOSENSITIVITY, MODULE_95, GOBP_ORGANELLE_LOCALIZATION, GOCC_CYTOPLASMIC_SIDE_OF_MEMBRANE, GOCC_SIDE_OF_MEMBRANE, MULLIGHAN_MLL_SIGNATURE_1_UP, SENGUPTA_EBNA1_ANTICORRELATED, TST1_01, MARTENS_TRETINOIN_RESPONSE_DN

GO Biological Process (4): 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 (2): identical protein binding (GO:0042802), 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
vacuolar localization	1
regulation of vesicle size	1
regulation of cellular component size	1
transport along microtubule	1
establishment of organelle localization	1
protein binding	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

468 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BORCS6	KXD1	Q9BQD3	995
BORCS6	BORCS5	Q969J3	993
BORCS6	SNAPIN	O95295	990
BORCS6	BORCS7	Q96B45	988
BORCS6	BLOC1S1	P78537	986
BORCS6	BLOC1S2	Q6QNY1	983
BORCS6	BORCS8	Q96FH0	970
BORCS6	ARL8B	Q9NVJ2	604
BORCS6	ARL5B	Q96KC2	583
BORCS6	ARL8A	Q96BM9	507
BORCS6	LAMTOR4	Q0VGL1	506
BORCS6	MPDU1	O75352	496
BORCS6	LAMTOR2	Q9Y2Q5	478
BORCS6	LAMTOR1	Q6IAA8	447
BORCS6	SLC38A9	Q8NBW4	420

IntAct

178 interactions, top by confidence:

A	B	Type	Score
LAMTOR4	LAMTOR5	psi-mi:“MI:0914”(association)	0.960
LAMTOR5	LAMTOR4	psi-mi:“MI:0914”(association)	0.960
LAMTOR1	LAMTOR5	psi-mi:“MI:0914”(association)	0.870
BORCS6	KXD1	psi-mi:“MI:0915”(physical association)	0.800
BORCS6	LAMTOR2	psi-mi:“MI:0915”(physical association)	0.740
LAMTOR3	LAMTOR5	psi-mi:“MI:0914”(association)	0.730
BORCS6	MOS	psi-mi:“MI:0915”(physical association)	0.670
MOS	BORCS6	psi-mi:“MI:0915”(physical association)	0.670
BORCS6	DISC1	psi-mi:“MI:0915”(physical association)	0.670
BORCS6	NDEL1	psi-mi:“MI:0915”(physical association)	0.670
DCTN2	BORCS6	psi-mi:“MI:0915”(physical association)	0.670
INSYN1	BORCS6	psi-mi:“MI:0915”(physical association)	0.670
RAB9A	CHM	psi-mi:“MI:2364”(proximity)	0.610
FBXO44	BORCS6	psi-mi:“MI:0915”(physical association)	0.600
BORCS6	FBXO44	psi-mi:“MI:0915”(physical association)	0.600
FCHSD2	BORCS6	psi-mi:“MI:0915”(physical association)	0.600
PKNOX1	BORCS6	psi-mi:“MI:0915”(physical association)	0.600
BORCS6	FCHSD2	psi-mi:“MI:0915”(physical association)	0.600
SHPRH	BORCS6	psi-mi:“MI:0915”(physical association)	0.560
EPS8	BORCS6	psi-mi:“MI:0915”(physical association)	0.560
BORCS6	SHPRH	psi-mi:“MI:0915”(physical association)	0.560
BORCS6	EPS8	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (308): C17orf59 (Two-hybrid), C17orf59 (Two-hybrid), C17orf59 (Two-hybrid), FBXO44 (Two-hybrid), SHPRH (Two-hybrid), C17orf59 (Affinity Capture-MS), C17orf59 (Affinity Capture-MS), C17orf59 (Affinity Capture-MS), KTN1 (Affinity Capture-MS), SPATS2 (Affinity Capture-MS), LUZP1 (Affinity Capture-MS), CEP250 (Affinity Capture-MS), UACA (Affinity Capture-MS), GOLGB1 (Affinity Capture-MS), BICD2 (Affinity Capture-MS)

ESM2 similar proteins: A2A699, A2A9T0, A2AEV7, A2AJA9, A6NKL6, A6NL88, A7MCY6, A8MVW0, C9J069, E9PZZ1, J3QNX5, O14492, O14511, O15169, O35615, O43541, O94983, P0C7U0, Q02779, Q03484, Q148V8, Q3SX20, Q5BJT1, Q5JTD0, Q5JU85, Q63HR2, Q66H43, Q66L44, Q69YU3, Q6DG50, Q6PDH0, Q6R6L0, Q6ZRV2, Q75VX8, Q7TN12, Q80VC9, Q80Y50, Q86UU1, Q8C3Q5, Q8C8T7

Diamond homologs: Q3SX20, Q66H43, Q96GS4, Q9D6W8

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 81 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
mTORC1-mediated signalling	5	49.6×	8e-06
Energy dependent regulation of mTOR by LKB1-AMPK	5	41.0×	1e-05
MTOR signalling	5	27.7×	6e-05
trans-Golgi Network Vesicle Budding	5	26.4×	6e-05
PTEN Regulation	5	23.8×	8e-05
Golgi Associated Vesicle Biogenesis	5	20.9×	1e-04
Amino acids regulate mTORC1	5	20.9×	1e-04
Regulation of PTEN gene transcription	5	18.6×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
anterograde synaptic vesicle transport	5	67.9×	8e-07
TORC1 signaling	5	55.0×	2e-06
lysosome localization	7	50.5×	3e-08
melanosome organization	5	44.4×	6e-06
anterograde axonal transport	5	39.8×	9e-06
positive regulation of TOR signaling	5	34.0×	2e-05
cellular response to amino acid stimulus	5	21.0×	2e-04
positive regulation of TORC1 signaling	5	20.2×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	49
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2683898	GRCh38/hg38 17p13.1(chr17:8171228-8185326)x1	Likely pathogenic

SpliceAI

9 predictions. Top by Δscore:

Variant	Effect	Δscore
17:8189241:G:GT	acceptor_gain	0.3000
17:8189242:T:TT	acceptor_gain	0.3000
17:8189333:C:CA	donor_gain	0.2900
17:8189014:AGGGT:A	donor_gain	0.2700
17:8189340:CA:C	donor_gain	0.2100
17:8189341:AA:A	donor_gain	0.2100
17:8189883:C:A	donor_gain	0.2100
17:8188986:TCCC:T	donor_gain	0.2000
17:8189053:T:A	donor_gain	0.2000

AlphaMissense

2253 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:8189493:A:C	F216L	1.000
17:8189493:A:T	F216L	1.000
17:8189495:A:G	F216L	1.000
17:8189193:C:A	K316N	0.999
17:8189193:C:G	K316N	0.999
17:8189197:A:T	I315N	0.999
17:8189234:C:G	A303P	0.999
17:8189239:C:G	R301P	0.999
17:8189262:G:C	S293R	0.999
17:8189262:G:T	S293R	0.999
17:8189264:T:G	S293R	0.999
17:8189467:A:G	I225T	0.999
17:8189494:A:C	F216C	0.999
17:8189494:A:G	F216S	0.999
17:8189528:C:G	G205R	0.999
17:8189199:G:C	S314R	0.998
17:8189199:G:T	S314R	0.998
17:8189201:T:G	S314R	0.998
17:8189213:C:G	A310P	0.998
17:8189467:A:C	I225S	0.998
17:8189528:C:A	G205C	0.998
17:8189186:A:G	Y319H	0.997
17:8189197:A:C	I315S	0.997
17:8189197:A:G	I315T	0.997
17:8189206:T:A	D312V	0.997
17:8189206:T:G	D312A	0.997
17:8189207:C:G	D312H	0.997
17:8189263:C:A	S293I	0.997
17:8189275:A:G	L289P	0.997
17:8189467:A:T	I225N	0.997

dbSNP variants (sampled 300 via entrez): RS1001107794 (17:8188015 A>G), RS1002388364 (17:8188224 T>A), RS1002771875 (17:8188539 T>C), RS1003060279 (17:8191182 C>G,T), RS1003627579 (17:8191982 G>A), RS1005520477 (17:8189575 G>A), RS1005553847 (17:8188971 C>T), RS1006500346 (17:8191046 A>T), RS1006528441 (17:8190000 C>G,T), RS1006883590 (17:8190259 A>T), RS1007475538 (17:8191539 T>A), RS1007938613 (17:8191264 A>G), RS1009329698 (17:8188259 A>G,T), RS1009785247 (17:8188609 G>A), RS1010332391 (17:8189717 C>T)

Disease associations

OMIM: gene MIM:616599 | disease phenotypes: MIM:614561, MIM:617667

GenCC curated gene-disease

Mondo (2): leukoencephalopathy with calcifications and cysts (MONDO:0013803), Fraser syndrome 3 (MONDO:0054739)

Orphanet (1): Leukoencephalopathy with calcifications and cysts (Orphanet:542310)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C000598644	Leukoencephalopathy Brain Calcifications and Cysts (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
afuresertib	increases expression	1
FR900359	increases phosphorylation	1
bisphenol A	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
corosolic acid	increases expression	1
abrine	increases expression	1
Sunitinib	increases expression	1
Leflunomide	decreases expression	1
Air Pollutants, Occupational	affects expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Cadmium	increases abundance, increases expression	1
Caffeine	decreases phosphorylation	1
Carcinogens	decreases expression	1
Cisplatin	increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Diazinon	increases methylation	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Indomethacin	affects cotreatment, increases expression	1
Niclosamide	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	decreases expression	1
1-Methyl-3-isobutylxanthine	increases expression, affects cotreatment	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SG10	HAP1 C17orf59 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02699190	Not specified	COMPLETED	LeukoSEQ: Whole Genome Sequencing as a First-Line Diagnostic Tool for Leukodystrophies
NCT03047369	Not specified	RECRUITING	The Myelin Disorders Biorepository Project