BLOC1S4

Summary

BLOC1S4 (biogenesis of lysosomal organelles complex 1 subunit 4, HGNC:24206) is a protein-coding gene on chromosome 4p16.1, encoding Biogenesis of lysosome-related organelles complex 1 subunit 4 (Q9NUP1). Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes.

This intronless gene encodes a protein that may play a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. A similar protein in mouse is a component of a protein complex termed biogenesis of lysosome-related organelles complex 1 (BLOC-1), and is a model for Hermansky-Pudlak syndrome. The encoded protein may play a role in intracellular vesicular trafficking.

Source: NCBI Gene 55330 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 52 total — 1 pathogenic
• MANE Select transcript: NM_018366

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24206
Approved symbol	BLOC1S4
Name	biogenesis of lysosomal organelles complex 1 subunit 4
Location	4p16.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ11230, BCAS4L
Ensembl gene	ENSG00000186222
Ensembl biotype	protein_coding
OMIM	605695
Entrez	55330

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000320776

RefSeq mRNA: 1 — MANE Select: NM_018366 NM_018366

CCDS: CCDS3393

Canonical transcript exons

ENST00000320776 — 1 exons

Exon	Start	End
ENSE00001281162	6716174	6717664

Expression profiles

Bgee: expression breadth ubiquitous, 224 present calls, max score 90.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.2126 / max 145.0338, expressed in 1805 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
46795	14.2126	1805

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	90.36	gold quality
granulocyte	CL:0000094	87.45	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.69	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	84.93	gold quality
mucosa of transverse colon	UBERON:0004991	84.50	gold quality
leukocyte	CL:0000738	84.41	gold quality
nasal cavity mucosa	UBERON:0001826	84.33	gold quality
monocyte	CL:0000576	84.22	gold quality
cartilage tissue	UBERON:0002418	82.98	gold quality
left adrenal gland	UBERON:0001234	82.92	gold quality
left adrenal gland cortex	UBERON:0035825	82.76	gold quality
right adrenal gland	UBERON:0001233	82.71	gold quality
stromal cell of endometrium	CL:0002255	82.67	gold quality
nasal cavity epithelium	UBERON:0005384	82.60	silver quality
right adrenal gland cortex	UBERON:0035827	82.46	gold quality
epithelial cell of pancreas	CL:0000083	82.11	silver quality
placenta	UBERON:0001987	82.02	gold quality
superficial temporal artery	UBERON:0001614	81.98	silver quality
left ovary	UBERON:0002119	81.90	gold quality
spleen	UBERON:0002106	81.78	gold quality
gastrocnemius	UBERON:0001388	81.69	gold quality
palpebral conjunctiva	UBERON:0001812	81.53	gold quality
apex of heart	UBERON:0002098	81.32	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.23	gold quality
adrenal cortex	UBERON:0001235	81.20	gold quality
descending thoracic aorta	UBERON:0002345	81.11	gold quality
right coronary artery	UBERON:0001625	81.07	gold quality
right ovary	UBERON:0002118	81.07	gold quality
bronchial epithelial cell	CL:0002328	81.05	gold quality
adrenal gland	UBERON:0002369	80.96	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.17

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

42 targeting BLOC1S4, 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-4668-3P	100.00	68.74	2635
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-1284	99.67	73.56	1353
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-889-3P	99.40	69.76	2103
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-888-5P	99.30	70.15	1855
HSA-MIR-1-5P	98.70	68.66	1017

Literature-anchored findings (GeneRIF, showing 1)

• Melanoma cells depleted of cappuccino protein have increased nuclear localization of cis-diaminedichloroplatinum II, increased nuclear DNA damage by platination, and increased apoptosis, resulting in increased treatment sensitivity. (PMID:22203954)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	bloc1s4	ENSDARG00000007597
mus_musculus	Bloc1s4	ENSMUSG00000060708
rattus_norvegicus	Bloc1s4	ENSRNOG00000054224
drosophila_melanogaster	Blos4	FBGN0036105

Paralogs (1): BCAS4 (ENSG00000124243)

Protein

Protein identifiers

Biogenesis of lysosome-related organelles complex 1 subunit 4 — Q9NUP1 (reviewed: Q9NUP1)

Alternative names: Protein cappuccino homolog

All UniProt accessions (1): Q9NUP1

UniProt curated annotations — full annotation on UniProt →

Function. Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes. In concert with the AP-3 complex, the BLOC-1 complex is required to target membrane protein cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals. The BLOC-1 complex, in association with SNARE proteins, is also proposed to be involved in neurite extension. Plays a role in intracellular vesicle trafficking.

Subunit / interactions. Interacts with BLOC1S5 and BLOC1S6. Component of the biogenesis of lysosome-related organelles complex 1 (BLOC-1) composed of BLOC1S1, BLOC1S2, BLOC1S3, BLOC1S4, BLOC1S5, BLOC1S6, DTNBP1/BLOC1S7 and SNAPIN/BLOC1S8. Octamer composed of one copy each BLOC1S1, BLOC1S2, BLOC1S3, BLOC1S4, BLOC1S5, BLOC1S6, DTNBP1/BLOC1S7 and SNAPIN/BLOC1S8. The BLOC-1 complex associates with the AP-3 protein complex and membrane protein cargos.

Subcellular location. Cytoplasm.

Similarity. Belongs to the BLOC1S4 family.

RefSeq proteins (1): NP_060836* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR024857	Cappuccino	Family

UniProt features (6 total): chain 1, region of interest 1, coiled-coil region 1, compositionally biased region 1, modified residue 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NUP1-F1	73.85	0.36

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): 165

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-432722	Golgi Associated Vesicle Biogenesis
R-HSA-199991	Membrane Trafficking
R-HSA-199992	trans-Golgi Network Vesicle Budding
R-HSA-5653656	Vesicle-mediated transport

MSigDB gene sets: 134 (showing top): GOBP_SYNAPTIC_VESICLE_LOCALIZATION, GOBP_AXO_DENDRITIC_TRANSPORT, GOBP_VESICLE_LOCALIZATION, GOBP_VESICLE_ORGANIZATION, GOBP_SYNAPTIC_VESICLE_CYTOSKELETAL_TRANSPORT, GOBP_PLATELET_ACTIVATION, GOBP_CELLULAR_PIGMENTATION, GOBP_NEUROGENESIS, REACTOME_MEMBRANE_TRAFFICKING, GOBP_ORGANELLE_TRANSPORT_ALONG_MICROTUBULE, GOBP_NEUROMUSCULAR_PROCESS_CONTROLLING_BALANCE, GOBP_PIGMENTATION, GOBP_WOUND_HEALING, GOBP_CELL_CELL_ADHESION, GOBP_VESICLE_CYTOSKELETAL_TRAFFICKING

GO Biological Process (6): anterograde axonal transport (GO:0008089), neuron projection development (GO:0031175), melanosome organization (GO:0032438), anterograde synaptic vesicle transport (GO:0048490), neuromuscular process controlling balance (GO:0050885), platelet aggregation (GO:0070527)

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

GO Cellular Component (4): cytoplasm (GO:0005737), cytosol (GO:0005829), BLOC-1 complex (GO:0031083), axon cytoplasm (GO:1904115)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
trans-Golgi Network Vesicle Budding	1
Vesicle-mediated transport	1
Membrane Trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
axonal transport	1
axon cytoplasm	1
neuron development	1
plasma membrane bounded cell projection organization	1
pigment granule organization	1
anterograde axonal transport	1
synaptic vesicle transport along microtubule	1
musculoskeletal movement	1
neuromuscular process	1
platelet activation	1
homotypic cell-cell adhesion	1
binding	1
intracellular anatomical structure	1
cytoplasm	1
BLOC complex	1
axon	1
neuron projection cytoplasm	1

Protein interactions and networks

STRING

298 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BLOC1S4	BLOC1S6	Q9UL45	974
BLOC1S4	BLOC1S1	P78537	916
BLOC1S4	BLOC1S3	Q6QNY0	892
BLOC1S4	BLOC1S2	Q6QNY1	871
BLOC1S4	BLOC1S5	Q8TDH9	866
BLOC1S4	SNAPIN	O95295	720
BLOC1S4	DTNBP1	Q96EV8	668
BLOC1S4	HPS6	Q86YV9	615
BLOC1S4	ESYT3	A0FGR9	464
BLOC1S4	LYST	Q99698	425
BLOC1S4	PTPMT1	Q8WUK0	409
BLOC1S4	TSPAN13	O95857	380
BLOC1S4	LENEP	Q9Y5L5	372
BLOC1S4	HPS3	Q969F9	369
BLOC1S4	VPS33A	Q96AX1	368

IntAct

46 interactions, top by confidence:

A	B	Type	Score
DTNBP1	SNAPIN	psi-mi:“MI:0914”(association)	0.900
BLOC1S6	BLOC1S1	psi-mi:“MI:0914”(association)	0.890
BLOC1S1	SNAPIN	psi-mi:“MI:0914”(association)	0.810
BLOC1S1	SNAPIN	psi-mi:“MI:0915”(physical association)	0.810
BRK1	HSBP1	psi-mi:“MI:0914”(association)	0.740
EXOC1	EXOC5	psi-mi:“MI:0914”(association)	0.730
FAM9C	NDC80	psi-mi:“MI:0914”(association)	0.670
BLOC1S6	BLOC1S4	psi-mi:“MI:0915”(physical association)	0.660
BLOC1S1	BLOC1S4	psi-mi:“MI:0914”(association)	0.660
BLOC1S1	BLOC1S4	psi-mi:“MI:0915”(physical association)	0.660
BLOC1S6	SNAPIN	psi-mi:“MI:0914”(association)	0.640
WASHC3	WASH3P	psi-mi:“MI:0914”(association)	0.530
BLOC1S5	SNAPIN	psi-mi:“MI:0914”(association)	0.530
BLOC1S4	SNAPIN	psi-mi:“MI:0915”(physical association)	0.370
BLOC1S2	BLOC1S4	psi-mi:“MI:0915”(physical association)	0.370
BLOC1S4	AIMP2	psi-mi:“MI:0915”(physical association)	0.370
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
POC1B	TACC1	psi-mi:“MI:0914”(association)	0.350
DTNBP1	AP3B1	psi-mi:“MI:0914”(association)	0.350
EXOC1	EXOC5	psi-mi:“MI:0914”(association)	0.350
	HLA-C	psi-mi:“MI:0914”(association)	0.350
EXOC1	RABGAP1L	psi-mi:“MI:0914”(association)	0.350
BLOC1S1	LAMTOR5	psi-mi:“MI:0914”(association)	0.350

BioGRID (28): BLOC1S4 (Affinity Capture-MS), BLOC1S4 (Affinity Capture-MS), BLOC1S4 (Affinity Capture-MS), BLOC1S4 (Affinity Capture-MS), BLOC1S4 (Affinity Capture-MS), BLOC1S4 (Affinity Capture-MS), BLOC1S4 (Two-hybrid), BLOC1S6 (Two-hybrid), SNAPIN (Two-hybrid), BLOC1S2 (Two-hybrid), BLOC1S4 (Two-hybrid), BLOC1S4 (Affinity Capture-RNA), BLOC1S4 (Affinity Capture-MS), BLOC1S4 (Affinity Capture-MS), BLOC1S4 (Affinity Capture-MS)

ESM2 similar proteins: A2ARS0, A6NH11, A6QQ91, C9JTQ0, D3ZVB0, D4A929, G3MZC5, O75064, O95996, P16386, P46062, P58660, Q02011, Q08DF2, Q16619, Q29RK8, Q2TBW5, Q2VPB7, Q3TAP4, Q3U0S6, Q3U1Y4, Q562E7, Q5TA50, Q5U651, Q60753, Q63086, Q64375, Q68J42, Q6P9B9, Q6ZS72, Q86YV0, Q8BH02, Q8BQU6, Q8C2K5, Q8CHT3, Q8K0R6, Q8K2B0, Q8N9M5, Q8VD26, Q92791

Diamond homologs: A0A096LPI5, A6NJG6, P51957, Q09FC8, Q5H9K5, Q68CZ1, Q8N9N2, Q8TDM0, Q8VED2, Q92918, Q96M98, Q96MD7, Q9NUP1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
BLOC1S4	“form complex”	BLOC-1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 35 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
trans-Golgi Network Vesicle Budding	5	57.7×	2e-06
Golgi Associated Vesicle Biogenesis	5	45.5×	4e-06
Membrane Trafficking	5	8.4×	6e-03
Vesicle-mediated transport	5	7.9×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
anterograde synaptic vesicle transport	7	216.8×	3e-13
melanosome organization	7	141.8×	4e-12
anterograde axonal transport	7	127.1×	7e-12
exocytosis	5	23.7×	5e-05
neuron projection development	6	22.9×	8e-06
cilium assembly	5	11.5×	1e-03
protein transport	8	11.0×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	49
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
253574	GRCh37/hg19 4p16.3-16.1(chr4:3776784-7361544)x1	Pathogenic

SpliceAI

101 predictions. Top by Δscore:

Variant	Effect	Δscore
4:6716638:G:GT	donor_gain	0.5900
4:6716760:GCAA:G	acceptor_gain	0.5800
4:6716676:TCACC:T	donor_gain	0.5700
4:6716627:GCC:G	donor_gain	0.5600
4:6716611:G:GT	donor_gain	0.5500
4:6716633:G:GG	donor_gain	0.5500
4:6716624:G:GT	donor_gain	0.5300
4:6716638:G:T	donor_gain	0.4800
4:6716199:G:GA	donor_gain	0.4700
4:6716677:C:A	donor_gain	0.4700
4:6716759:A:AG	acceptor_gain	0.4700
4:6716760:G:GG	acceptor_gain	0.4700
4:6716763:A:G	acceptor_gain	0.4700
4:6716632:C:CG	donor_gain	0.4600
4:6716662:G:GT	donor_gain	0.4600
4:6716198:T:TA	donor_gain	0.4500
4:6716218:T:TA	donor_gain	0.4100
4:6716219:A:AA	donor_gain	0.4100
4:6716175:G:GT	donor_gain	0.3900
4:6716637:G:GT	donor_gain	0.3800
4:6716722:G:GT	donor_gain	0.3800
4:6716558:G:GT	donor_gain	0.3700
4:6716612:A:T	donor_gain	0.3700
4:6716752:G:T	acceptor_gain	0.3700
4:6716775:CGAGG:C	acceptor_gain	0.3700
4:6716844:GT:G	acceptor_gain	0.3700
4:6716639:A:T	donor_gain	0.3600
4:6716761:C:T	donor_gain	0.3600
4:6716713:G:GT	donor_gain	0.3500
4:6716679:C:G	donor_gain	0.3400

AlphaMissense

1410 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:6716504:T:C	F99L	0.994
4:6716506:C:A	F99L	0.994
4:6716506:C:G	F99L	0.994
4:6716505:T:C	F99S	0.991
4:6716484:T:C	L92P	0.990
4:6716571:T:C	I121T	0.990
4:6716487:T:C	L93P	0.985
4:6716505:T:G	F99C	0.984
4:6716813:T:C	F202L	0.984
4:6716815:T:A	F202L	0.984
4:6716815:T:G	F202L	0.984
4:6716814:T:C	F202S	0.982
4:6716613:T:A	I135N	0.980
4:6716630:T:C	F141L	0.979
4:6716632:C:A	F141L	0.979
4:6716632:C:G	F141L	0.979
4:6716571:T:G	I121S	0.978
4:6716676:T:A	V156D	0.978
4:6716622:T:C	L138P	0.976
4:6716684:G:C	A159P	0.975
4:6716571:T:A	I121N	0.972
4:6716631:T:C	F141S	0.972
4:6716832:T:C	F208S	0.972
4:6716315:A:C	S36R	0.971
4:6716317:C:A	S36R	0.971
4:6716317:C:G	S36R	0.971
4:6716499:A:T	D97V	0.971
4:6716831:T:C	F208L	0.971
4:6716833:C:A	F208L	0.971
4:6716833:C:G	F208L	0.971

dbSNP variants (sampled 300 via entrez): RS1000477244 (4:6715103 C>T), RS1001527974 (4:6716079 G>A), RS1003029427 (4:6714859 G>C), RS1003497961 (4:6716159 G>A,T), RS1003524854 (4:6718136 G>T), RS1003954976 (4:6715464 T>C), RS1004341838 (4:6715732 A>C,G), RS1004365064 (4:6714712 T>A), RS1004415809 (4:6714371 A>T), RS1004674215 (4:6716523 T>C,G), RS1005429166 (4:6715805 A>T), RS1005626795 (4:6716362 C>A,T), RS1005957400 (4:6717413 A>G), RS1006346509 (4:6717573 GTA>G,GTATA), RS1006881643 (4:6717056 A>G)

Disease associations

OMIM: gene MIM:605695 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009391_1793	Metabolite levels	2.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0010449	3-methyladipic acid measurement
EFO:0010524	pimelic acid measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
methylmercuric chloride	decreases expression	1
sodium arsenite	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
Air Pollutants	decreases expression, increases abundance	1
Cadmium	increases expression, increases abundance	1
Diethylstilbestrol	decreases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	decreases expression	1
Cadmium Chloride	increases expression, increases abundance	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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