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 — automated summary from GO annotations (Alliance of Genome Resources).

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): 35 total — 3 pathogenic, 1 likely-pathogenic
• GTEx eGene: eQTL in 45 tissues, sQTL in 6 (q < 0.05)
• Phenotypes (HPO): 113
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.10 (unconstrained)
• 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: 30 — 23 protein_coding, 3 retained_intron, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000462790

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 2, TSL 3: 4

ENST00000462790, ENST00000462498, ENST00000477565, ENST00000488252, ENST00000494489, ENST00000585679, ENST00000588208, ENST00000591398, ENST00000591566, ENST00000892307, ENST00000892308, ENST00000916350, ENST00000963658, ENST00000963659, ENST00000984866, ENST00000984867, ENST00001038567, ENST00001038568, ENST00001038569, ENST00001038570, ENST00001069921, ENST00001069922, ENST00001069924, ENST00001092611, ENST00001092612, ENST00001092613, ENST00001092614, ENST00001092615, ENST00001092616, ENST00001140534

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.

Highest expression (Bgee): prefrontal cortex, anterior cingulate cortex, cingulate cortex, Brodmann (1909) area 9, frontal lobe.

Genetic regulation across tissues (GTEx eQTL / sQTL)

BORCS8 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 45 tissues and its splicing (sQTL) in 6 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 51 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Nerve Tibial	eqtl	6.4e-42	+0.33	19:19179021:A:G
Thyroid	eqtl	1.7e-35	+0.37	19:19177929:G:A
Adipose Subcutaneous	eqtl	3.3e-27	+0.26	19:19179021:A:G
Cells Cultured fibroblasts	eqtl	2.1e-25	+0.25	19:19177929:G:A
Skin Sun Exposed Lower leg	eqtl	3.7e-24	+0.26	19:19179021:A:G
Skin Not Sun Exposed Suprapubic	eqtl	7.9e-20	+0.28	19:19179021:A:G
Esophagus Muscularis	eqtl	1.3e-17	+0.28	19:19179306:C:T
Colon Sigmoid	eqtl	2.9e-17	+0.31	19:19179306:C:T
Breast Mammary Tissue	eqtl	4.9e-16	+0.25	19:19168558:C:A
Colon Transverse	eqtl	3.2e-15	+0.33	19:19168558:C:A
Brain Cortex	eqtl	7.0e-15	+0.29	19:19168643:C:G
Testis	eqtl	7.5e-15	+0.34	19:19168558:C:A
Pituitary	eqtl	2.2e-14	+0.37	19:19168558:C:A
Artery Aorta	eqtl	3.8e-14	+0.30	19:19168558:C:A
Artery Tibial	eqtl	5.5e-14	+0.20	19:19168558:C:A
Cells Cultured fibroblasts	sqtl	9.7e-14	-0.61	19:19151491:C:T
Brain Caudate basal ganglia	eqtl	3.9e-13	+0.23	19:19171376:T:G
Lung	eqtl	6.2e-13	+0.22	19:19168558:C:A
Prostate	eqtl	4.5e-11	+0.33	19:19168558:C:A
Brain Nucleus accumbens basal ganglia	eqtl	3.0e-10	+0.25	19:19179021:A:G

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
180128	22.6054	1810

Top tissues by expression

showing 100 of 284 tissues 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
forebrain	UBERON:0001890	87.28	gold quality
telencephalon	UBERON:0001893	87.22	gold quality
heart left ventricle	UBERON:0002084	87.18	gold quality
muscle of leg	UBERON:0001383	87.11	gold quality
monocyte	CL:0000576	87.01	gold quality
left coronary artery	UBERON:0001626	87.00	gold quality
thyroid gland	UBERON:0002046	86.86	gold quality
mononuclear cell	CL:0000842	86.83	gold quality
leukocyte	CL:0000738	86.79	gold quality
cardiac ventricle	UBERON:0002082	86.79	gold quality
body of stomach	UBERON:0001161	86.77	gold quality
right adrenal gland	UBERON:0001233	86.77	gold quality
right lobe of liver	UBERON:0001114	86.70	gold quality
brain	UBERON:0000955	86.66	gold quality
bronchial epithelial cell	CL:0002328	86.59	gold quality
left adrenal gland cortex	UBERON:0035825	86.58	gold quality
coronary artery	UBERON:0001621	86.53	gold quality
left adrenal gland	UBERON:0001234	86.47	gold quality
right adrenal gland cortex	UBERON:0035827	86.32	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.31	gold quality
spinal cord	UBERON:0002240	86.16	gold quality
substantia nigra	UBERON:0002038	86.07	gold quality
cardiac atrium	UBERON:0002081	86.04	gold quality
spleen	UBERON:0002106	86.00	gold quality
cerebellar hemisphere	UBERON:0002245	85.96	gold quality
right coronary artery	UBERON:0001625	85.93	gold quality
cerebellar cortex	UBERON:0002129	85.89	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	85.87	gold quality
upper lobe of left lung	UBERON:0008952	85.83	gold quality
lower esophagus muscularis layer	UBERON:0035833	85.82	gold quality
lower esophagus	UBERON:0013473	85.81	gold quality
heart	UBERON:0000948	85.80	gold quality
adrenal cortex	UBERON:0001235	85.74	gold quality
thoracic aorta	UBERON:0001515	85.62	gold quality
ascending aorta	UBERON:0001496	85.60	gold quality
omental fat pad	UBERON:0010414	85.59	gold quality
peritoneum	UBERON:0002358	85.55	gold quality
adipose tissue of abdominal region	UBERON:0007808	85.53	gold quality
upper lobe of lung	UBERON:0008948	85.47	gold quality
transverse colon	UBERON:0001157	85.43	gold quality
muscle layer of sigmoid colon	UBERON:0035805	85.42	gold quality
right lung	UBERON:0002167	85.33	gold quality
esophagus	UBERON:0001043	85.31	gold quality
cerebellum	UBERON:0002037	85.28	gold quality
esophagus mucosa	UBERON:0002469	85.22	gold quality
left uterine tube	UBERON:0001303	85.18	gold quality
aorta	UBERON:0000947	85.17	gold quality
midbrain	UBERON:0001891	85.15	gold quality
popliteal artery	UBERON:0002250	84.95	gold quality
minor salivary gland	UBERON:0001830	84.94	gold quality
primary visual cortex	UBERON:0002436	84.94	gold quality
tibial artery	UBERON:0007610	84.94	gold quality
Ammon’s horn	UBERON:0001954	84.74	gold quality
tibial nerve	UBERON:0001323	84.72	gold quality
adipose tissue	UBERON:0001013	84.71	gold quality
right uterine tube	UBERON:0001302	84.61	gold quality
adrenal gland	UBERON:0002369	84.60	gold quality
subcutaneous adipose tissue	UBERON:0002190	84.38	gold quality
cortical plate	UBERON:0005343	84.30	gold quality
descending thoracic aorta	UBERON:0002345	84.27	gold quality
stomach	UBERON:0000945	84.24	gold quality
temporal lobe	UBERON:0001871	84.11	gold quality
amniotic fluid	UBERON:0000173	84.08	gold quality
connective tissue	UBERON:0002384	84.08	gold quality
ectocervix	UBERON:0012249	84.07	gold quality
anatomical system	UBERON:0000467	84.06	gold quality
multicellular organism	UBERON:0000468	84.02	gold quality
material anatomical entity	UBERON:0000465	84.01	gold quality
mucosa of stomach	UBERON:0001199	83.99	gold quality
stromal cell of endometrium	CL:0002255	83.97	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Pons	tissue	55.2
Medulla oblongata	tissue	55.0
Spinal cord	tissue	54.9
Superior colliculi	tissue	53.3
Corpus callosum	tissue	52.7
Substantia nigra	tissue	50.9
Midbrain	tissue	50.8
Thalamus	tissue	48.5
Hypothalamus	tissue	47.6
Periaqueductal gray	tissue	47.5
Putamen	tissue	44.7
Basal ganglia	tissue	42.7	not detected
Septum	tissue	41.9
Hippocampal formation	tissue	40.5
Cerebral cortex	tissue	40.4	high
Somatosensory cortex	tissue	40.4
Occipital cortex	tissue	39.9
Ventral forebrain	tissue	37.3
Temporal cortex	tissue	36.0
Prefrontal cortex	tissue	35.2
Entorhinal cortex	tissue	35.0
Retrosplenial and cingulate cortex	tissue	34.0
Insular cortex	tissue	33.9
Motor cortex	tissue	33.7
Retrosplenial cortex	tissue	33.7
Amygdala	tissue	32.3
Olfactory bulb	tissue	31.4
Cerebellum	tissue	26.2	not detected
Pituitary gland	tissue	23.3
Locus coeruleus	tissue	19.3
Tongue	tissue	16.7
Frontal cortex	tissue	16.5
Heart muscle	tissue	16.3	medium
Postcentral gyrus	tissue	15.9
Caudate putamen	tissue	15.7
Parathyroid gland	tissue	15.0	medium
Bone marrow	tissue	14.9	low
Skeletal muscle	tissue	13.3	medium
Hippocampus	tissue	12.9	not detected
Nucleus accumbens	tissue	12.8
Adipose tissue	tissue	11.9	low
Lymph node	tissue	11.7	not detected
Thyroid gland	tissue	11.7	medium
Adrenal gland	tissue	11.7	medium
Choroid plexus	tissue	11.6
Thymus	tissue	11.3
Vagina	tissue	11.2	medium
Appendix	tissue	11.1	medium
Esophagus	tissue	11.0	high
Pancreas	tissue	10.5	high
Duodenum	tissue	10.3	medium
Kidney	tissue	10.2	medium
Fallopian tube	tissue	10.2	medium
Urinary bladder	tissue	10.1	medium
Lung	tissue	9.9	low
Liver	tissue	9.3	not detected
Stomach 1	tissue	9.2	medium
Salivary gland	tissue	9.2	high
Colon	tissue	9.1	high
Skin 1	tissue	8.3	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Ventral spinal cord (54.9), White matter (52.7), Dorsal spinal cord (49.9), Ventral hippocampus (40.5), Dorsal hippocampus (39.7).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting BORCS8 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

18 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 0.000613, LOEUF 1.1, missense Z 0.0571 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000462790 — one region, missense o/e 1.00.

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

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1919618) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 1 distinct phenotype terms.

Mouse phenotype (MP)	Records
preweaning lethality, incomplete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Tetraodon nigroviridis	Q4S3C1	90.7%	Diamond
Nematostella vectensis	A7SGF0	45.0%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
NR2C2AP	protein-coding	126382
SLC25A42	protein-coding	284439
BORCS8-MEF2B	protein-coding	4207
TMEM161A	protein-coding	54929
RFXANK	protein-coding	8625
NCAN	protein-coding	1463
HAPLN4	protein-coding	404037
TM6SF2	protein-coding	53345
MEF2B	protein-coding	100271849

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

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): vesicles

Antibody reliability (HPA): IH approved · IF approved

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)

Type	Positions
Phosphoserine	109

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

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 (3): cytoplasmic side of lysosomal membrane (GO:0098574), BORC complex (GO:0099078), lysosomal membrane (GO:0005765)

GO top-level categories

13 GO namespaces:

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
lysosome	1
lytic vacuole membrane	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 2 of 9 annotations. The rest are phylogenetic / computational / electronic (IEA).

2 experimentally-supported GO terms:

GO term	NS	Evidence
heart development	BP	expression pattern
BORC complex	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 360 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BORCS8	KXD1	Q9BQD3	832
BORCS8	BORCS6	Q96GS4	823
BORCS8	BORCS5	Q969J3	821
BORCS8	SNAPIN	O95295	773
BORCS8	BORCS7	Q96B45	757
BORCS8	BLOC1S2	Q6QNY1	740
BORCS8	BLOC1S1	P78537	721
BORCS8	ARL5B	Q96KC2	613
BORCS8	ARL8B	Q9NVJ2	610
BORCS8	PRPSAP1	Q14558	530
BORCS8	ARL8A	Q96BM9	513
BORCS8	MEF2B	Q02080	491
BORCS8	LAMTOR4	Q0VGL1	478
BORCS8	KCTD19	Q17RG1	477
BORCS8	LAMTOR1	Q6IAA8	459

IntAct

Human interaction partners of BORCS8 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

8 partners by confidence:

Partner	Interaction type	MIscore	Records
TEX11	physical association	0.700	10
CTAG1A	physical association	0.560	5
AGR2	physical association	0.560	3
MESD	physical association	0.560	3
SNAPIN	association	0.530	1
P2RX5	physical association	0.490	2
SH3PXD2B	association	0.350	1
TP73	association	0.350	1

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
BORC complex	8	BORCS5, BORCS6, BORCS7, BORCS8, KXD1, SNAPIN, BLOC1S1, BLOC1S2

Disease & clinical

Genetic variants

Variant evidence for BORCS8: 35 ClinVar records (4 pathogenic / likely pathogenic); 7 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	1
Uncertain significance	30
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (4)

Showing all 4 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
4850390	NM_001145784.2(BORCS8):c.202G>T (p.Glu68Ter)	Likely pathogenic	criteria provided, single submitter	1
3363149	NM_001145784.2(BORCS8):c.71_75dup (p.Asn26fs)	Pathogenic	no assertion criteria provided	1
3363151	NM_001145784.2(BORCS8):c.196A>C (p.Thr66Pro)	Pathogenic	no assertion criteria provided	1
3363152	NM_001145784.2(BORCS8):c.124T>C (p.Ser42Pro)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore BORCS8’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 33 predictions of 583):

Position(s)	Effect	Δscore	Sites
19:19186891–19186892	donor_loss	1.0000	5
19:19187006–19187007	acceptor_loss	1.0000	5
19:19187034	acceptor_gain	1.0000
19:19192088	donor_gain	1.0000
19:19182571–19182572	donor_loss	0.9900	6
19:19182684–19182685	acceptor_loss	0.9900	6
19:19186032–19186033	donor_loss	0.9900	5
19:19187006	acceptor_loss	0.9900
19:19187010	acceptor_gain	0.9900
19:19187014–19187016	acceptor_gain	0.9900	2

AlphaMissense

386 missense substitutions predicted likely pathogenic (of 783 scored), across 88 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M53	9	0.873	0.992
H38	8	0.998	0.999
N26	8	0.938	0.997
F84	8	0.885	0.987
F17	8	0.827	0.995
H49	8	0.824	0.989
E37	7	0.989	0.998
E27	7	0.979	0.999
Q36	7	0.938	0.998
E19	7	0.900	0.992
E57	7	0.837	0.915
E68	7	0.830	0.983
D52	7	0.801	0.900
P28	6	0.995	0.999
P44	6	0.986	0.994
V39	6	0.972	0.999
R41	6	0.966	0.999
K50	6	0.958	0.997
K9	6	0.928	0.991
A31	6	0.912	0.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	6.73e-06
Pancreatic Adenocarcinoma (TCGA)	favorable	8.65e-05
Rectum Adenocarcinoma (validation)	favorable	0.000906

Disease associations

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

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
neurodegeneration, infantile-onset, with optic atrophy and brain abnormalities	Strong	Autosomal recessive	2
inherited neurodegenerative disorder	Limited	Autosomal recessive

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (9 panels, 6 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

9 panels:

Panel	Rating
DDG2P	green
Hereditary spastic paraplegia, childhood onset	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Optic neuropathy	green
Early onset or syndromic epilepsy	amber
Paediatric disorders	amber
Unexplained death in infancy and sudden unexplained death in childhood	amber

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

HPO phenotypes

showing 60 of 113 phenotypes (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
HP:0000750	Delayed speech and language development
HP:0000758	Abnormal nonverbal communicative behavior
HP:0000939	Osteoporosis
HP:0000958	Dry skin
HP:0001238	Slender finger
HP:0001250	Seizure
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001272	Cerebellar atrophy
HP:0001284	Areflexia
HP:0001290	Generalized hypotonia
HP:0001300	Parkinsonism
HP:0001324	Muscle weakness
HP:0001332	Dystonia
HP:0001336	Myoclonus
HP:0001337	Tremor
HP:0001344	Absent speech
HP:0001348	Brisk reflexes
HP:0001508	Failure to thrive
HP:0001845	Overlapping toe
HP:0002015	Dysphagia
HP:0002059	Cerebral atrophy
HP:0002061	Lower limb spasticity
HP:0002072	Chorea
HP:0002091	Restrictive ventilatory defect
HP:0002187	Profound intellectual disability
HP:0002209	Sparse scalp hair
HP:0002236	Frontal upsweep of hair
HP:0002280	Enlarged cisterna magna
HP:0002376	Developmental regression

GWAS associations

7 associations:

Study	Trait	p-value
GCST008103_170	Bipolar disorder	1e-9
GCST008115_31	Bipolar I disorder	3e-9
GCST003434_1	Obsessive-compulsive symptoms	3e-8
GCST007706_37	Mean arterial pressure	6e-8
GCST007706_101	Mean arterial pressure	9e-8
GCST008116_4	Bipolar II disorder	4e-6
GCST008163_436	Height	4e-6

EFO canonical traits (from GWAS)

4 canonical traits:

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 disease descriptors:

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 (CPIC guideline: no)

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	affects cotreatment, increases expression	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	increases expression, decreases reaction	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	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)

Via MONDO — disease-level, not drug-specific.

1 trials:

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