BLOC1S3

Summary

BLOC1S3 (biogenesis of lysosomal organelles complex 1 subunit 3, HGNC:20914) is a protein-coding gene on chromosome 19q13.32, encoding Biogenesis of lysosome-related organelles complex 1 subunit 3 (Q6QNY0). 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 protein that is a component of the BLOC1 multi-subunit protein complex. This complex is necessary for the biogenesis of specialized organelles of the endosomal-lysosomal system, including platelet dense granules and melanosomes. Mutations in this gene cause Hermansky-Pudlak syndrome 8, a disease characterized by lysosomal storage defects, bleeding due to platelet storage pool deficiency, and oculocutaneous albinism.

Source: NCBI Gene 388552 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Hermansky-Pudlak syndrome 8 (Strong, GenCC)
• GWAS associations: 9
• Clinical variants (ClinVar): 262 total — 5 pathogenic
• Phenotypes (HPO): 30
• MANE Select transcript: NM_212550

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20914
Approved symbol	BLOC1S3
Name	biogenesis of lysosomal organelles complex 1 subunit 3
Location	19q13.32
Locus type	gene with protein product
Status	Approved
Aliases	BLOS3, HPS8
Ensembl gene	ENSG00000189114
Ensembl biotype	protein_coding
OMIM	609762
Entrez	388552

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000433642, ENST00000587722, ENST00000588362, ENST00000591569, ENST00000592910, ENST00000593083, ENST00000884249

RefSeq mRNA: 1 — MANE Select: NM_212550 NM_212550

CCDS: CCDS12656

Canonical transcript exons

ENST00000433642 — 2 exons

Exon	Start	End
ENSE00001510180	45178784	45178831
ENSE00001772844	45179288	45181800

Expression profiles

Bgee: expression breadth ubiquitous, 225 present calls, max score 92.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.6033 / max 311.7722, expressed in 1814 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176392	13.7083	1806
176393	1.8950	1021

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	92.23	gold quality
secondary oocyte	CL:0000655	90.09	gold quality
upper arm skin	UBERON:0004263	86.76	silver quality
granulocyte	CL:0000094	86.58	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.46	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.97	gold quality
blood	UBERON:0000178	82.67	gold quality
skin of leg	UBERON:0001511	81.76	gold quality
leukocyte	CL:0000738	80.85	gold quality
ileal mucosa	UBERON:0000331	80.66	gold quality
cortical plate	UBERON:0005343	80.64	gold quality
skin of abdomen	UBERON:0001416	80.59	gold quality
monocyte	CL:0000576	80.23	gold quality
mucosa of transverse colon	UBERON:0004991	80.03	gold quality
zone of skin	UBERON:0000014	79.85	gold quality
stromal cell of endometrium	CL:0002255	79.75	gold quality
apex of heart	UBERON:0002098	79.20	gold quality
spleen	UBERON:0002106	78.98	gold quality
right adrenal gland cortex	UBERON:0035827	78.44	gold quality
prefrontal cortex	UBERON:0000451	77.89	gold quality
kidney epithelium	UBERON:0004819	77.64	gold quality
right adrenal gland	UBERON:0001233	77.44	gold quality
cardiac muscle of right atrium	UBERON:0003379	77.39	gold quality
popliteal artery	UBERON:0002250	77.21	gold quality
tibial artery	UBERON:0007610	77.19	gold quality
right coronary artery	UBERON:0001625	77.07	gold quality
left ventricle myocardium	UBERON:0006566	77.02	gold quality
islet of Langerhans	UBERON:0000006	76.80	gold quality
aorta	UBERON:0000947	76.79	gold quality
lymph node	UBERON:0000029	76.67	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.68
E-GEOD-124858	no	284.75

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR1, FOS, JUN, SP1, SP3

miRNA regulators (miRDB)

82 targeting BLOC1S3, 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-6851-5P	100.00	65.63	1294
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-379-3P	99.69	69.60	1524

Literature-anchored findings (GeneRIF, showing 3)

• A germline mutation in BLOC1S3/reduced pigmentation causes a novel variant of Hermansky-Pudlak syndrome (HPS8). (PMID:16385460)
• BLOC-2 and BLOC-3 were destabilized due to the mutation of these Hermansky-Pudlak syndrome (HPS) genes which are so far the only reported causative genes in Chinese HPS patients (PMID:30387913)
• Novel variants in the BLOC1S3 gene in patients presenting a mild form of Hermansky-Pudlak syndrome. (PMID:32687635)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	bloc1s3	ENSDARG00000068828
danio_rerio		ENSDARG00000097344
mus_musculus	Bloc1s3	ENSMUSG00000057667
rattus_norvegicus	Bloc1s3	ENSRNOG00000017463

Protein

Protein identifiers

Biogenesis of lysosome-related organelles complex 1 subunit 3 — Q6QNY0 (reviewed: Q6QNY0)

All UniProt accessions (2): K7EN58, Q6QNY0

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, 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. Interacts directly with BLOC1S2.

Subcellular location. Cytoplasm.

Disease relevance. Hermansky-Pudlak syndrome 8 (HPS8) [MIM:614077] 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 BLOC1S3 family.

RefSeq proteins (1): NP_997715* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR017245	BLOC-1_complex_su-3	Family

Pfam: PF15753

UniProt features (7 total): compositionally biased region 3, modified residue 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6QNY0-F1	71.38	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 (2): 63, 65

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: 210 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_SYNAPTIC_VESICLE_LOCALIZATION, GOBP_PIGMENT_GRANULE_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_PIGMENTATION, GOBP_WOUND_HEALING, GOBP_SECRETORY_GRANULE_ORGANIZATION

GO Biological Process (16): eye development (GO:0001654), anterograde axonal transport (GO:0008089), response to xenobiotic stimulus (GO:0009410), platelet activation (GO:0030168), neuron projection development (GO:0031175), melanosome transport (GO:0032402), melanosome organization (GO:0032438), positive regulation of natural killer cell activation (GO:0032816), secretion of lysosomal enzymes (GO:0033299), endosome to melanosome transport (GO:0035646), pigmentation (GO:0043473), anterograde synaptic vesicle transport (GO:0048490), platelet dense granule organization (GO:0060155), blood coagulation (GO:0007596), developmental pigmentation (GO:0048066), protein transmembrane transport (GO:0071806)

GO Molecular Function (2): transmembrane protein transporter activity (GO:0008320), protein binding (GO:0005515)

GO Cellular Component (5): cytosol (GO:0005829), transport vesicle (GO:0030133), BLOC-1 complex (GO:0031083), axon cytoplasm (GO:1904115), cytoplasm (GO:0005737)

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
sensory organ development	1
visual system development	1
axonal transport	1
axon cytoplasm	1
response to chemical	1
cell activation	1
blood coagulation	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
natural killer cell activation	1
regulation of natural killer cell activation	1
positive regulation of lymphocyte activation	1
protein secretion	1
endosome to pigment granule transport	1
biological_process	1
anterograde axonal transport	1
synaptic vesicle transport along microtubule	1
secretory granule organization	1
hemostasis	1
wound healing	1
coagulation	1
pigmentation	1
protein transport	1
transmembrane transport	1
macromolecule transmembrane transporter activity	1
protein transmembrane transport	1
protein transporter activity	1
binding	1
cytoplasm	1
endomembrane system	1
cytoplasmic vesicle	1
BLOC complex	1
axon	1
neuron projection cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

540 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BLOC1S3	SNAPIN	O95295	999
BLOC1S3	BLOC1S2	Q6QNY1	999
BLOC1S3	BLOC1S1	P78537	999
BLOC1S3	BLOC1S6	Q9UL45	999
BLOC1S3	DTNBP1	Q96EV8	998
BLOC1S3	HPS3	Q969F9	959
BLOC1S3	HPS6	Q86YV9	951
BLOC1S3	HPS5	Q9UPZ3	950
BLOC1S3	HPS4	Q9NQG7	921
BLOC1S3	BLOC1S4	Q9NUP1	892
BLOC1S3	BLOC1S5	Q8TDH9	874
BLOC1S3	AP3B1	O00203	836
BLOC1S3	LYST	Q99698	683
BLOC1S3	TYRP1	P17643	639
BLOC1S3	MARK4	Q96L34	608

IntAct

32 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
BLOC1S6	SNAPIN	psi-mi:“MI:0914”(association)	0.640
BLOC1S5	SNAPIN	psi-mi:“MI:0914”(association)	0.530
DNALI1	GSN	psi-mi:“MI:0914”(association)	0.510
BLOC1S2	BLOC1S3	psi-mi:“MI:0915”(physical association)	0.480
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
DTNBP1	AP3B1	psi-mi:“MI:0914”(association)	0.350
BCAS4	SNAPIN	psi-mi:“MI:0914”(association)	0.350
MBLAC2	STAT3	psi-mi:“MI:0914”(association)	0.350
BLOC1S3	SNAPIN	psi-mi:“MI:0914”(association)	0.350
ENTHD1	C1orf226	psi-mi:“MI:0914”(association)	0.350
S100A2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
HSPA2	HGS	psi-mi:“MI:0914”(association)	0.350
BLOC1S1	LAMTOR5	psi-mi:“MI:0914”(association)	0.350
BLOC1S6	HSBP1	psi-mi:“MI:0914”(association)	0.350
MBLAC2	CD63	psi-mi:“MI:0914”(association)	0.350
BLOC1S6	KCNN4	psi-mi:“MI:0914”(association)	0.350
DTNBP1	DUSP14	psi-mi:“MI:0914”(association)	0.350
BLOC1S5	SRGAP2	psi-mi:“MI:0914”(association)	0.350
DTNBP1	SNAP23	psi-mi:“MI:0914”(association)	0.350

BioGRID (32): BLOC1S3 (Affinity Capture-MS), BLOC1S3 (Affinity Capture-MS), BLOC1S3 (Affinity Capture-MS), BLOC1S3 (Affinity Capture-MS), BLOC1S3 (Affinity Capture-MS), BLOC1S3 (Affinity Capture-MS), BLOC1S3 (Affinity Capture-MS), BLOC1S3 (Affinity Capture-RNA), BLOC1S3 (Co-purification), BLOC1S3 (Affinity Capture-Western), BLOC1S3 (Affinity Capture-Western), BLOC1S3 (Affinity Capture-Western), BLOC1S1 (Affinity Capture-Western), BLOC1S2 (Affinity Capture-Western), SNAPIN (Affinity Capture-Western)

ESM2 similar proteins: A0A140LIT1, A0A1B0GVG4, A0A494C0Y3, A0JNH6, A0JNN8, A1A5D9, A2ARS0, A5A769, A5PJP1, A6NC98, A7YWC8, C9JTQ0, O15049, O35764, O95502, P0C7N4, P0DPE3, P58660, Q0P5D1, Q1HCM0, Q2TAC2, Q3LUD3, Q3LUD4, Q3TMW1, Q3UMT1, Q4QRL3, Q5BLP8, Q5JTB6, Q6QNY0, Q6QZQ4, Q8BP01, Q8C7U1, Q8CHW5, Q8K262, Q8N283, Q8N6Y0, Q8TAT2, Q8TER5, Q8TF21, Q91XV7

Diamond homologs: A5A769, A5PJP1, Q5U5M8, Q6QNY0

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
BLOC1S3	“form complex”	BLOC-1	binding
TFEB	“up-regulates quantity by expression”	BLOC1S3	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 27 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	74.6×	7e-07
Golgi Associated Vesicle Biogenesis	5	58.9×	1e-06
Membrane Trafficking	5	10.9×	3e-03
Vesicle-mediated transport	5	10.2×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
anterograde synaptic vesicle transport	7	301.7×	2e-14
melanosome organization	7	197.3×	3e-13
anterograde axonal transport	7	176.9×	5e-13
neuron projection development	6	31.9×	2e-06
positive regulation of gene expression	5	8.4×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	0
Uncertain significance	125
Likely benign	99
Benign	13

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
1489	NM_212550.5(BLOC1S3):c.448del (p.Gln150fs)	Pathogenic
431167	NM_212550.5(BLOC1S3):c.131C>A (p.Ser44Ter)	Pathogenic
870134	NM_212550.5(BLOC1S3):c.444_467del (p.Gln150_Ala157del)	Pathogenic
870630	NM_212550.5(BLOC1S3):c.338_341del (p.Leu113fs)	Pathogenic
929862	NM_212550.5(BLOC1S3):c.385_403del (p.Ser129fs)	Pathogenic

SpliceAI

1206 predictions. Top by Δscore:

Variant	Effect	Δscore
19:45213354:CTGC:C	acceptor_gain	1.0000
19:45213355:TGC:T	acceptor_gain	1.0000
19:45213356:GC:G	acceptor_gain	1.0000
19:45213357:CC:C	acceptor_gain	1.0000
19:45213357:CCTG:C	acceptor_loss	1.0000
19:45213358:C:CC	acceptor_gain	1.0000
19:45216068:CTCAC:C	donor_loss	1.0000
19:45216069:TCACC:T	donor_loss	1.0000
19:45216070:CACCT:C	donor_loss	1.0000
19:45216071:A:AG	donor_loss	1.0000
19:45216072:C:G	donor_loss	1.0000
19:45216190:GACTC:G	acceptor_gain	1.0000
19:45216191:ACTC:A	acceptor_gain	1.0000
19:45216191:ACTCC:A	acceptor_gain	1.0000
19:45216192:CTC:C	acceptor_gain	1.0000
19:45216192:CTCC:C	acceptor_gain	1.0000
19:45216192:CTCCT:C	acceptor_gain	1.0000
19:45216193:TC:T	acceptor_gain	1.0000
19:45216193:TCCT:T	acceptor_gain	1.0000
19:45216194:CC:C	acceptor_gain	1.0000
19:45216195:C:A	acceptor_loss	1.0000
19:45216195:C:CC	acceptor_gain	1.0000
19:45216198:C:CT	acceptor_gain	1.0000
19:45179939:GGGG:G	donor_gain	0.9900
19:45179940:GGGG:G	donor_gain	0.9900
19:45187327:CCAG:C	acceptor_gain	0.9900
19:45187328:CAG:C	acceptor_gain	0.9900
19:45187329:A:AG	acceptor_gain	0.9900
19:45187329:AGA:A	acceptor_gain	0.9900
19:45187329:AGAGC:A	acceptor_gain	0.9900

AlphaMissense

1246 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:45179690:T:G	Y132D	0.965
19:45179853:T:C	I186T	0.964
19:45179484:C:T	T63I	0.955
19:45179796:T:A	L167H	0.951
19:45179634:T:C	L113P	0.944
19:45179853:T:A	I186N	0.944
19:45179753:G:A	G153R	0.942
19:45179753:G:C	G153R	0.942
19:45179544:T:A	L83H	0.941
19:45179690:T:A	Y132N	0.941
19:45179826:T:A	V177E	0.940
19:45179834:T:C	C180R	0.939
19:45179853:T:G	I186S	0.938
19:45179775:T:A	V160E	0.928
19:45179700:C:A	A135E	0.923
19:45179844:T:A	L183Q	0.923
19:45179642:A:C	S116R	0.920
19:45179644:C:A	S116R	0.920
19:45179644:C:G	S116R	0.920
19:45179793:A:T	D166V	0.915
19:45179796:T:C	L167P	0.911
19:45179765:G:C	A157P	0.909
19:45179823:T:A	I176N	0.909
19:45179634:T:A	L113Q	0.907
19:45179679:T:A	V128E	0.903
19:45179631:G:C	R112P	0.900
19:45179469:G:T	G58V	0.899
19:45179469:G:A	G58E	0.893
19:45179473:A:C	E59D	0.893
19:45179473:A:T	E59D	0.893

dbSNP variants (sampled 300 via entrez): RS1000026004 (19:45216897 C>T), RS1000067633 (19:45209719 C>G), RS1000112435 (19:45189323 G>A), RS1000181026 (19:45181098 C>G), RS1000357655 (19:45183629 T>TC), RS1000392209 (19:45204976 C>T), RS1000471139 (19:45214653 C>T), RS1000485626 (19:45189411 G>A), RS1000594057 (19:45192973 A>G), RS1000597135 (19:45195052 T>C), RS1000637685 (19:45181374 C>T), RS1000670929 (19:45204882 C>T), RS1000718631 (19:45198854 G>T), RS1000847915 (19:45210395 G>A,T), RS1000872706 (19:45200643 G>C,T)

Disease associations

OMIM: gene MIM:609762 | disease phenotypes: MIM:614077, MIM:620943, MIM:203300

GenCC curated gene-disease

Disease	Classification	Inheritance
Hermansky-Pudlak syndrome 8	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
Hermansky-Pudlak syndrome 8	Moderate	AR

Mondo (3): Hermansky-Pudlak syndrome 8 (MONDO:0013560), brain malformation renal syndrome (MONDO:0975799), Hermansky-Pudlak syndrome (MONDO:0019312)

Orphanet (2): Hermansky-Pudlak syndrome (Orphanet:79430), Hermansky-Pudlak syndrome type 8 (Orphanet:231537)

HPO phenotypes

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

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000132	Menorrhagia
HP:0000225	Gingival bleeding
HP:0000421	Epistaxis
HP:0000483	Astigmatism
HP:0000540	Hypermetropia
HP:0000543	Optic disc pallor
HP:0000545	Myopia
HP:0000565	Esotropia
HP:0000577	Exotropia
HP:0000635	Blue irides
HP:0000639	Nystagmus
HP:0000666	Horizontal nystagmus
HP:0000978	Bruising susceptibility
HP:0001022	Albinism
HP:0001107	Ocular albinism
HP:0002218	Silver-gray hair
HP:0003540	Impaired platelet aggregation
HP:0003577	Congenital onset
HP:0007513	Generalized hypopigmentation
HP:0007663	Reduced visual acuity
HP:0007750	Hypoplasia of the fovea
HP:0008499	High hypermetropia
HP:0011003	High myopia
HP:0012043	Pendular nystagmus
HP:0012805	Iris transillumination defect
HP:0030138	Excessive bleeding from superficial cuts
HP:0030139	Excessive bleeding after a venipuncture
HP:0031729	Moderate hypermetropia
HP:0500041	Myopic astigmatism

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST000337_21	Quantitative traits	2.000000e-06
GCST000337_22	Quantitative traits	4.000000e-07
GCST005950_15	Body mass index x sex x age interaction (4df test)	2.000000e-10
GCST005951_56	Body mass index	1.000000e-06
GCST005952_8	Body mass index (age>50)	9.000000e-12
GCST005954_4	Body mass index x age interaction	2.000000e-07
GCST007827_13	Alzheimer’s disease or HDL levels (pleiotropy)	7.000000e-22
GCST007827_3	Alzheimer’s disease or HDL levels (pleiotropy)	1.000000e-97
GCST007827_8	Alzheimer’s disease or HDL levels (pleiotropy)	3.000000e-36

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004458	C-reactive protein measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004340	body mass index
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004612	high density lipoprotein cholesterol 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: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation	2
Smoke	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
arsenite	increases reaction, affects binding	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
pentabromodiphenyl ether	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
Leflunomide	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Thimerosal	decreases expression	1
Thiram	decreases expression	1
Urethane	increases expression	1
Valproic Acid	increases expression	1
Cyclosporine	increases expression	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	increases expression	1

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