BLOC1S5

Summary

BLOC1S5 (biogenesis of lysosomal organelles complex 1 subunit 5, HGNC:18561) is a protein-coding gene on chromosome 6p24.3, encoding Biogenesis of lysosome-related organelles complex 1 subunit 5 (Q8TDH9). 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 gene encodes a component of BLOC-1 (biogenesis of lysosome-related organelles complex 1). Components of this complex are involved in the biogenesis of organelles such as melanosomes and platelet-dense granules. A mouse model for Hermansky-Pudlak Syndrome is mutated in the murine version of this gene. Alternative splicing results in multiple transcript variants. Read-through transcription exists between this gene and the upstream EEF1E1 (eukaryotic translation elongation factor 1 epsilon 1) gene, as well as with the downstream TXNDC5 (thioredoxin domain containing 5) gene.

Source: NCBI Gene 63915 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Hermansky-Pudlak syndrome 11 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 65 total — 10 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 17
• Druggable target: yes
• MANE Select transcript: NM_201280

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18561
Approved symbol	BLOC1S5
Name	biogenesis of lysosomal organelles complex 1 subunit 5
Location	6p24.3
Locus type	gene with protein product
Status	Approved
Aliases	MU, dJ303A1.3
Ensembl gene	ENSG00000188428
Ensembl biotype	protein_coding
OMIM	607289
Entrez	63915

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000244777, ENST00000397457, ENST00000475998, ENST00000486432, ENST00000543936, ENST00000627748, ENST00000853651, ENST00000853652

RefSeq mRNA: 3 — MANE Select: NM_201280 NM_001199322, NM_001199323, NM_201280

CCDS: CCDS4506, CCDS75394

Canonical transcript exons

ENST00000397457 — 5 exons

Exon	Start	End
ENSE00001125397	8064265	8064389
ENSE00001482342	8013567	8015828
ENSE00003607013	8041139	8041268
ENSE00003747451	8026367	8026425
ENSE00003800407	8062534	8062616

Expression profiles

Bgee: expression breadth ubiquitous, 257 present calls, max score 99.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.6387 / max 133.3829, expressed in 1779 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
71638	10.6387	1779

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	99.00	gold quality
visceral pleura	UBERON:0002401	94.50	gold quality
kidney epithelium	UBERON:0004819	94.49	gold quality
parietal pleura	UBERON:0002400	94.41	gold quality
tibia	UBERON:0000979	94.18	gold quality
tendon of biceps brachii	UBERON:0008188	93.99	gold quality
endothelial cell	CL:0000115	93.86	gold quality
germinal epithelium of ovary	UBERON:0001304	93.70	gold quality
sperm	CL:0000019	93.53	gold quality
superficial temporal artery	UBERON:0001614	93.48	gold quality
trabecular bone tissue	UBERON:0002483	93.46	gold quality
amniotic fluid	UBERON:0000173	93.31	gold quality
tendon	UBERON:0000043	92.77	gold quality
ileal mucosa	UBERON:0000331	92.68	gold quality
calcaneal tendon	UBERON:0003701	92.68	gold quality
epithelial cell of pancreas	CL:0000083	92.55	silver quality
layer of synovial tissue	UBERON:0007616	92.52	gold quality
skin of hip	UBERON:0001554	92.22	gold quality
renal medulla	UBERON:0000362	91.98	gold quality
epithelium of nasopharynx	UBERON:0001951	91.72	gold quality
palpebral conjunctiva	UBERON:0001812	91.63	gold quality
thymus	UBERON:0002370	91.54	gold quality
oral cavity	UBERON:0000167	91.48	gold quality
jejunal mucosa	UBERON:0000399	91.13	gold quality
oviduct epithelium	UBERON:0004804	90.51	gold quality
cartilage tissue	UBERON:0002418	89.65	gold quality
esophagus squamous epithelium	UBERON:0006920	89.53	gold quality
mucosa of paranasal sinus	UBERON:0005030	89.48	gold quality
seminal vesicle	UBERON:0000998	89.22	gold quality
nipple	UBERON:0002030	89.11	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.76
E-MTAB-4850	no	334.76

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SPI1

miRNA regulators (miRDB)

92 targeting BLOC1S5, 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-1277-5P	100.00	73.95	5056
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699

Literature-anchored findings (GeneRIF, showing 3)

• BLOC1S5 pathogenic variants cause a new type of Hermansky-Pudlak syndrome. (PMID:32565547)
• A novel BLOC1S5-related HPS-11 patient and zebrafish with bloc1s5 disruption. (PMID:34058075)
• A Novel Likely Pathogenic Variant in the BLOC1S5 Gene Associated with Hermansky-Pudlak Syndrome Type 11 and an Overview of Human BLOC-1 Deficiencies. (PMID:34685610)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	bloc1s5	ENSDARG00000111747
mus_musculus	Bloc1s5	ENSMUSG00000038982
rattus_norvegicus	Bloc1s5	ENSRNOG00000016497
drosophila_melanogaster	Muted	FBGN0083967

Protein

Protein identifiers

Biogenesis of lysosome-related organelles complex 1 subunit 5 — Q8TDH9 (reviewed: Q8TDH9)

Alternative names: Protein Muted homolog

All UniProt accessions (4): A0A0A0MTN6, A0A0D9SEU2, G5E931, Q8TDH9

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 BLOC1S4, DTNBP1/BLOC1S7 and PI4K2A. 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. Interacts with BLOC1S6.

Disease relevance. Hermansky-Pudlak syndrome 11 (HPS11) [MIM:619172] A form of Hermansky-Pudlak syndrome, a genetically heterogeneous autosomal recessive disorder characterized by oculocutaneous albinism, bleeding due to platelet storage pool deficiency, and lysosomal storage defects. This syndrome results from defects of diverse cytoplasmic organelles including melanosomes, platelet dense granules and lysosomes. Ceroid storage in the lungs is associated with pulmonary fibrosis, a common cause of premature death in individuals with HPS. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the BLOC1S5 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8TDH9-1	1	yes
Q8TDH9-2	2
Q8TDH9-3	3

RefSeq proteins (3): NP_001186251, NP_001186252, NP_958437* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR017243	Bloc1s5	Family

Pfam: PF14942

UniProt features (8 total): splice variant 3, initiator methionine 1, chain 1, region of interest 1, coiled-coil region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TDH9-F1	87.86	0.70

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): 2

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 221 (showing top): GOBP_SYNAPTIC_VESICLE_LOCALIZATION, GOBP_PIGMENT_GRANULE_LOCALIZATION, GOBP_AXO_DENDRITIC_TRANSPORT, GOBP_VESICLE_LOCALIZATION, chr6p24, GOBP_VESICLE_ORGANIZATION, GOBP_SYNAPTIC_VESICLE_CYTOSKELETAL_TRANSPORT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_CELLULAR_PIGMENTATION, GOBP_NEUROGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_ORGANELLE_TRANSPORT_ALONG_MICROTUBULE, GOBP_PIGMENTATION, GOBP_ANIMAL_ORGAN_MORPHOGENESIS

GO Biological Process (10): anterograde axonal transport (GO:0008089), vesicle-mediated transport (GO:0016192), neuron projection development (GO:0031175), melanosome transport (GO:0032402), melanosome organization (GO:0032438), otolith morphogenesis (GO:0032474), endosome to melanosome transport (GO:0035646), anterograde synaptic vesicle transport (GO:0048490), positive regulation of pigment cell differentiation (GO:0050942), developmental pigmentation (GO:0048066)

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

GO Cellular Component (4): transport vesicle (GO:0030133), BLOC-1 complex (GO:0031083), axon cytoplasm (GO:1904115), microvesicle (GO:1990742)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
axonal transport	1
axon cytoplasm	1
transport	1
cellular process	1
neuron development	1
plasma membrane bounded cell projection organization	1
melanosome localization	1
establishment of melanosome localization	1
pigment granule transport	1
pigment granule organization	1
inner ear morphogenesis	1
embryonic morphogenesis	1
otolith development	1
endosome to pigment granule transport	1
anterograde axonal transport	1
synaptic vesicle transport along microtubule	1
positive regulation of cell differentiation	1
positive regulation of developmental pigmentation	1
pigment cell differentiation	1
regulation of pigment cell differentiation	1
pigmentation	1
binding	1
endomembrane system	1
cytoplasmic vesicle	1
BLOC complex	1
axon	1
neuron projection cytoplasm	1
extracellular vesicle	1

Protein interactions and networks

STRING

632 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BLOC1S5	BLOC1S6	Q9UL45	988
BLOC1S5	SNAPIN	O95295	924
BLOC1S5	BLOC1S3	Q6QNY0	874
BLOC1S5	BLOC1S4	Q9NUP1	866
BLOC1S5	BLOC1S1	P78537	855
BLOC1S5	BLOC1S2	Q6QNY1	832
BLOC1S5	DTNBP1	Q96EV8	781
BLOC1S5	HPS3	Q969F9	710
BLOC1S5	HPS5	Q9UPZ3	599
BLOC1S5	HPS6	Q86YV9	589
BLOC1S5	H7C0V5	H7C0V5	543
BLOC1S5	TXNDC5	Q8NBS9	541
BLOC1S5	AP3D1	O14617	514
BLOC1S5	CCDC180	Q9P1Z9	453
BLOC1S5	VPS33A	Q96AX1	432

IntAct

75 interactions, top by confidence:

A	B	Type	Score
DTNBP1	SNAPIN	psi-mi:“MI:0914”(association)	0.900
BLOC1S2	SNAPIN	psi-mi:“MI:0914”(association)	0.830
BLOC1S1	SNAPIN	psi-mi:“MI:0914”(association)	0.810
BLOC1S1	SNAPIN	psi-mi:“MI:0915”(physical association)	0.810
BLOC1S5	DTNBP1	psi-mi:“MI:0915”(physical association)	0.770
BLOC1S5	TSNAX	psi-mi:“MI:0915”(physical association)	0.720
TSNAX	BLOC1S5	psi-mi:“MI:0915”(physical association)	0.720
BLOC1S2	BLOC1S5	psi-mi:“MI:0915”(physical association)	0.700
BLOC1S6	SNAPIN	psi-mi:“MI:0914”(association)	0.640
TGIF2LY	PGP	psi-mi:“MI:0914”(association)	0.640
ABI3	BLOC1S5	psi-mi:“MI:0915”(physical association)	0.560
HSBP1	BLOC1S5	psi-mi:“MI:0915”(physical association)	0.560
PBX2	BLOC1S5	psi-mi:“MI:0915”(physical association)	0.560
PKNOX1	BLOC1S5	psi-mi:“MI:0915”(physical association)	0.560
OIP5	BLOC1S5	psi-mi:“MI:0915”(physical association)	0.560
BLOC1S5	ABI3	psi-mi:“MI:0915”(physical association)	0.560
BLOC1S5	ABI2	psi-mi:“MI:0915”(physical association)	0.560
BLOC1S5	SMARCD1	psi-mi:“MI:0915”(physical association)	0.560
BORCS6	HSBP1	psi-mi:“MI:0914”(association)	0.530
KXD1	HIP1	psi-mi:“MI:0914”(association)	0.530
BLOC1S5	SNAPIN	psi-mi:“MI:0914”(association)	0.530
KXD1	TRAK2	psi-mi:“MI:0914”(association)	0.530

BioGRID (61): BLOC1S5 (Affinity Capture-MS), BLOC1S5 (Two-hybrid), BLOC1S5 (Affinity Capture-MS), BLOC1S5 (Affinity Capture-MS), BLOC1S5 (Affinity Capture-MS), BLOC1S5 (Affinity Capture-MS), BLOC1S5 (Affinity Capture-MS), BLOC1S5 (Affinity Capture-MS), BLOC1S5 (Affinity Capture-MS), BLOC1S5 (Affinity Capture-MS), BLOC1S5 (Affinity Capture-MS), BLOC1S5 (Affinity Capture-MS), BLOC1S5 (Affinity Capture-Western), BLOC1S5 (Affinity Capture-Western), BLOC1S5 (Affinity Capture-Western)

ESM2 similar proteins: A1L3H4, A5A777, A6ZRZ4, A9ULR1, B2GV52, B3LNU5, B4R1Z3, C5E2E7, C7GUN6, C8ZGE4, F4I0Z6, H2QII6, O14043, O48767, O94656, P33716, P34606, P48232, P49792, Q01050, Q01649, Q03954, Q10006, Q17695, Q18012, Q2TBY0, Q4R8E8, Q4V8S9, Q50HP3, Q5I0J4, Q60JJ0, Q61806, Q6CQ94, Q6FMH8, Q750P7, Q8BXX9, Q8GX05, Q8IR45, Q8R015, Q8TA52

Diamond homologs: A1L3H4, A5A777, A9ULR1, B2GV52, Q54TC6, Q5ZK77, Q8R015, Q8TDH9, A7SPE8

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
BLOC1S5	“form complex”	BLOC-1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 49 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	40.9×	9e-06
Golgi Associated Vesicle Biogenesis	6	38.8×	1e-06

GO biological processes:

GO term	Partners	Fold	FDR
anterograde synaptic vesicle transport	7	157.7×	4e-12
melanosome organization	7	103.1×	3e-11
anterograde axonal transport	7	92.5×	5e-11
platelet dense granule organization	5	76.6×	2e-07
lysosome localization	6	71.8×	1e-08
neuron projection development	6	16.6×	6e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	6
Uncertain significance	40
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (16)

Variant ID	HGVS	Classification
147369	GRCh38/hg38 6p25.3-24.3(chr6:163083-9525496)x3	Pathogenic
253511	GRCh37/hg19 6p25.3-24.1(chr6:204009-11608587)x1	Pathogenic
3065169	NM_201280.3(BLOC1S5):c.2T>G (p.Met1Arg)	Pathogenic
563149	GRCh37/hg19 6p25.1-24.3(chr6:4990661-10358695)x1	Pathogenic
563154	GRCh37/hg19 6p25.1-24.2(chr6:6990611-11276452)x1	Pathogenic
58411	GRCh38/hg38 6p25.3-24.3(chr6:165675-9036034)x1	Pathogenic
58423	GRCh38/hg38 6p25.1-24.3(chr6:4427090-8391140)x1	Pathogenic
813287	GRCh37/hg19 6p24.3(chr6:8023117-8042179)x0	Pathogenic
870631	NM_201280.3(BLOC1S5):c.345del (p.Val116fs)	Pathogenic
996012	NM_201280.2:c.196-678_384+3483del	Pathogenic
154190	GRCh38/hg38 6p25.3-24.2(chr6:156974-11550817)x3	Likely pathogenic
2431939	NM_201280.3(BLOC1S5):c.19G>T (p.Glu7Ter)	Likely pathogenic
2630117	NM_201280.3(BLOC1S5):c.326-2A>C	Likely pathogenic
3236053	NM_201280.3(BLOC1S5):c.154del (p.Val52fs)	Likely pathogenic
4845846	NM_201280.3(BLOC1S5):c.352A>T (p.Arg118Ter)	Likely pathogenic
563144	GRCh37/hg19 6p25.3-24.3(chr6:1860928-8884071)x3	Likely pathogenic

SpliceAI

1253 predictions. Top by Δscore:

Variant	Effect	Δscore
6:8026426:C:CC	acceptor_gain	1.0000
6:8041133:A:AC	donor_gain	1.0000
6:8041134:C:CC	donor_gain	1.0000
6:8041135:TCA:T	donor_loss	1.0000
6:8041135:TCACA:T	donor_loss	1.0000
6:8041136:CA:C	donor_loss	1.0000
6:8041137:A:AC	donor_gain	1.0000
6:8041137:ACAT:A	donor_gain	1.0000
6:8041138:C:CA	donor_gain	1.0000
6:8041138:CA:C	donor_gain	1.0000
6:8041138:CAT:C	donor_gain	1.0000
6:8041138:CATC:C	donor_gain	1.0000
6:8041138:CATCT:C	donor_gain	1.0000
6:8041265:TTTCC:T	acceptor_loss	1.0000
6:8041266:TTCC:T	acceptor_loss	1.0000
6:8041266:TTCCT:T	acceptor_loss	1.0000
6:8041267:TCCTA:T	acceptor_loss	1.0000
6:8041268:CCT:C	acceptor_loss	1.0000
6:8041269:C:CC	acceptor_gain	1.0000
6:8041269:CT:C	acceptor_loss	1.0000
6:8041269:CTATT:C	acceptor_loss	1.0000
6:8062532:A:AC	donor_gain	1.0000
6:8062533:C:CC	donor_gain	1.0000
6:8062533:CTT:C	donor_gain	1.0000
6:8062613:AGAT:A	acceptor_gain	1.0000
6:8062613:AGATC:A	acceptor_loss	1.0000
6:8062614:GAT:G	acceptor_gain	1.0000
6:8062614:GATC:G	acceptor_loss	1.0000
6:8062615:ATC:A	acceptor_loss	1.0000
6:8062616:TC:T	acceptor_loss	1.0000

AlphaMissense

1253 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:8041262:G:T	R68S	0.989
6:8062537:A:C	F64L	0.988
6:8062537:A:T	F64L	0.988
6:8062539:A:G	F64L	0.988
6:8062574:A:T	V52D	0.987
6:8041261:C:G	R68P	0.984
6:8062534:T:A	E65D	0.982
6:8062534:T:G	E65D	0.982
6:8062592:A:G	L46P	0.982
6:8062538:A:G	F64S	0.981
6:8062594:C:A	R45S	0.981
6:8062594:C:G	R45S	0.981
6:8062543:T:A	K62N	0.980
6:8062543:T:G	K62N	0.980
6:8062565:C:T	G55D	0.980
6:8062556:C:G	R58P	0.979
6:8062584:G:C	H49D	0.977
6:8062579:T:A	R50S	0.976
6:8062579:T:G	R50S	0.976
6:8062582:G:C	H49Q	0.976
6:8062582:G:T	H49Q	0.976
6:8062595:C:A	R45M	0.976
6:8015704:A:G	L170P	0.975
6:8041252:C:G	R71P	0.975
6:8062542:C:T	E63K	0.975
6:8062595:C:G	R45T	0.975
6:8041249:T:A	E72V	0.974
6:8062566:C:G	G55R	0.972
6:8015717:C:G	A166P	0.968
6:8062544:T:A	K62I	0.968

dbSNP variants (sampled 300 via entrez): RS1000004139 (6:8060950 G>A), RS1000123610 (6:8045929 A>T), RS1000149057 (6:8063996 G>A), RS1000163360 (6:8027414 T>A,C), RS1000164648 (6:8054999 C>A,T), RS1000184240 (6:8023923 A>G), RS1000312636 (6:8018516 C>G,T), RS1000315343 (6:8058358 A>G), RS1000345173 (6:8049003 C>T), RS1000362594 (6:8058039 T>C), RS1000410482 (6:8046148 A>C), RS1000570324 (6:8042068 A>G), RS1000587281 (6:8043214 T>C), RS1000693219 (6:8021405 C>A), RS1000708455 (6:8038099 A>G)

Disease associations

OMIM: gene MIM:607289 | disease phenotypes: MIM:619172, MIM:203300

GenCC curated gene-disease

Disease	Classification	Inheritance
Hermansky-Pudlak syndrome 11	Strong	Autosomal recessive
Hermansky-Pudlak syndrome	Moderate	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Hermansky-Pudlak syndrome 11	Definitive	AR

Mondo (2): Hermansky-Pudlak syndrome 11 (MONDO:0030903), Hermansky-Pudlak syndrome (MONDO:0019312)

Orphanet (1): Hermansky-Pudlak syndrome (Orphanet:79430)

HPO phenotypes

17 total (17 of 17 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000132	Menorrhagia
HP:0000225	Gingival bleeding
HP:0000421	Epistaxis
HP:0000486	Strabismus
HP:0000613	Photophobia
HP:0000639	Nystagmus
HP:0000978	Bruising susceptibility
HP:0000995	Melanocytic nevus
HP:0001022	Albinism
HP:0001107	Ocular albinism
HP:0002286	Fair hair
HP:0007663	Reduced visual acuity
HP:0007750	Hypoplasia of the fovea
HP:0008320	Impaired collagen-induced platelet aggregation
HP:0012805	Iris transillumination defect
HP:0033535	Reduced platelet dense granules

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002097_28	Coronary artery calcification	3.000000e-06
GCST002759_8	Motion sickness	3.000000e-18
GCST009172_2	Response to (pegylated) interferon in HBeAg-negative hepatitis B	3.000000e-06
GCST009391_260	Metabolite levels	6.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004723	coronary artery calcification
EFO:0006928	motion sickness
EFO:0007859	response to interferon
EFO:0010426	triacylglycerol 54:8 measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D022861	Hermanski-Pudlak Syndrome	C11.270.040.545.400; C15.378.100.100.515; C15.378.100.685.400; C15.378.140.735.400; C15.378.463.735.400; C16.320.099.515; C16.320.290.040.100.400; C16.320.565.100.102.100.400; C16.320.850.080.100.400; C17.800.621.440.102.100.400; C17.800.827.080.100.400; C18.452.648.100.102.100.400

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724755 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, decreases expression	1
Zoledronic Acid	increases expression	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Phenylmercuric Acetate	affects cotreatment, decreases expression	1
Tretinoin	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
Cadmium Chloride	decreases expression	1
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	1
Permethrin	increases expression	1
Volatile Organic Compounds	affects cotreatment, increases oxidation	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697390	Binding	Inhibition of MUTED (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04193592	PHASE2	UNKNOWN	Efficacy and Safety of Pirfenidone Treatment in HPS-ILD
NCT00467831	PHASE1/PHASE2	TERMINATED	Pilot Study of a Multi-Drug Regimen for Severe Pulmonary Fibrosis in Hermansky-Pudlak Syndrome
NCT00001456	Not specified	RECRUITING	Clinical and Basic Investigations Into Hermansky-Pudlak Syndrome
NCT00084305	Not specified	ACTIVE_NOT_RECRUITING	Analysis of Specimens From Individuals With Pulmonary Fibrosis
NCT01417520	Not specified	COMPLETED	Clinical and Pathophysiological Investigations Into Erdheim Chester Disease
NCT02368340	Not specified	COMPLETED	A Longitudinal Study of Hermansky-Pudlak Syndrome Pulmonary Fibrosis