HPS3

Summary

HPS3 (HPS3 biogenesis of lysosomal organelles complex 2 subunit 1, HGNC:15597) is a protein-coding gene on chromosome 3q24, encoding BLOC-2 complex member HPS3 (Q969F9). Involved in early stages of melanosome biogenesis and maturation.

This gene encodes a protein containing a potential clathrin-binding motif, consensus dileucine signals, and tyrosine-based sorting signals for targeting to vesicles of lysosomal lineage. The encoded protein may play a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. Mutations in this gene are associated with Hermansky-Pudlak syndrome type 3.

Source: NCBI Gene 84343 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Hermansky-Pudlak syndrome 3 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 1,114 total — 87 pathogenic, 112 likely-pathogenic
• Phenotypes (HPO): 17
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_032383

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15597
Approved symbol	HPS3
Name	HPS3 biogenesis of lysosomal organelles complex 2 subunit 1
Location	3q24
Locus type	gene with protein product
Status	Approved
Aliases	SUTAL, BLOC2S1
Ensembl gene	ENSG00000163755
Ensembl biotype	protein_coding
OMIM	606118
Entrez	84343

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 13 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000296051, ENST00000460120, ENST00000460822, ENST00000462030, ENST00000478525, ENST00000486530, ENST00000494327, ENST00000870868, ENST00000870869, ENST00000870870, ENST00000870871, ENST00000870872, ENST00000940664, ENST00000940665, ENST00000940666, ENST00000940667, ENST00000960204, ENST00000960205

RefSeq mRNA: 2 — MANE Select: NM_032383 NM_001308258, NM_032383

CCDS: CCDS3140, CCDS77836

Canonical transcript exons

ENST00000296051 — 17 exons

Exon	Start	End
ENSE00001077971	149158666	149158846
ENSE00001077973	149155107	149155215
ENSE00001077979	149167893	149167983
ENSE00001077980	149157350	149157531
ENSE00001077982	149163842	149163949
ENSE00001077983	149162690	149162878
ENSE00001077984	149153494	149153648
ENSE00001077986	149167034	149167240
ENSE00001077987	149162148	149162333
ENSE00001246195	149172095	149173732
ENSE00001246257	149160046	149160279
ENSE00001913355	149129638	149129940
ENSE00003469635	149141017	149141188
ENSE00003497633	149140004	149140498
ENSE00003504795	149145354	149145546
ENSE00003513628	149141295	149141380
ENSE00003573155	149150599	149150680

Expression profiles

Bgee: expression breadth ubiquitous, 245 present calls, max score 94.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.0228 / max 162.8225, expressed in 1810 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
39135	20.8519	1810
39136	0.1017	29
39137	0.0692	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	94.98	gold quality
secondary oocyte	CL:0000655	92.09	gold quality
jejunal mucosa	UBERON:0000399	91.70	gold quality
oviduct epithelium	UBERON:0004804	91.28	gold quality
nasal cavity epithelium	UBERON:0005384	90.44	gold quality
lymph node	UBERON:0000029	89.89	gold quality
duodenum	UBERON:0002114	89.65	gold quality
monocyte	CL:0000576	89.61	gold quality
leukocyte	CL:0000738	89.60	gold quality
oocyte	CL:0000023	89.57	gold quality
spleen	UBERON:0002106	89.08	gold quality
pigmented layer of retina	UBERON:0001782	88.75	gold quality
islet of Langerhans	UBERON:0000006	88.69	gold quality
germinal epithelium of ovary	UBERON:0001304	88.46	gold quality
calcaneal tendon	UBERON:0003701	88.07	gold quality
endometrium	UBERON:0001295	88.03	gold quality
kidney epithelium	UBERON:0004819	87.83	gold quality
adrenal tissue	UBERON:0018303	87.54	gold quality
vermiform appendix	UBERON:0001154	87.40	gold quality
body of uterus	UBERON:0009853	87.38	gold quality
granulocyte	CL:0000094	87.33	gold quality
descending thoracic aorta	UBERON:0002345	87.13	gold quality
visceral pleura	UBERON:0002401	87.13	gold quality
right adrenal gland	UBERON:0001233	87.04	gold quality
stromal cell of endometrium	CL:0002255	87.03	gold quality
blood	UBERON:0000178	86.89	gold quality
left adrenal gland	UBERON:0001234	86.79	gold quality
right adrenal gland cortex	UBERON:0035827	86.73	gold quality
palpebral conjunctiva	UBERON:0001812	86.63	gold quality
liver	UBERON:0002107	86.60	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.92

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

63 targeting HPS3, 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-6867-5P	100.00	82.21	3464
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-219A-5P	99.91	73.36	735
HSA-MIR-4782-3P	99.88	73.31	735
HSA-MIR-6766-3P	99.88	73.38	732
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-548AI	99.69	69.24	1494
HSA-MIR-548BA	99.69	69.14	1514
HSA-MIR-570-5P	99.69	69.24	1494
HSA-MIR-7161-5P	99.68	68.92	1592

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 9)

• mutational analysis in Ashkenazi Jews with Hermansky-Pudlak syndrome 3 (PMID:11590544)
• Description of mutations in HPS genes that cause Hermansky-Pudlak syndrome (review) (PMID:12125811)
• HPS4 but not HPS3 associates with HPS1 in a complex, which we term biogenesis of lysosome-related organelles complex 3 (BLOC-3) (PMID:12847290)
• Component of BLOC-2. Results suggest a common biological basis underlying the pathogenesis of HPS-3, -5 and -6 disease. (PMID:15030569)
• A specific subset of melanocyte proteins are aberrantly trafficked throughout the HPS-3 melanocyte and may be responsible for the reduction in melanin synthesis. (PMID:15632015)
• HPS3 associates with clathrin, predominantly on small clathrin-containing vesicles in the perinuclear region. This association most likely occurs directly via a functional clathrin-binding domain in HPS3. (PMID:16159387)
• HPS3 mutation is associated with high hypopigmentation in Hermansky-Pudlak syndrome. (PMID:27593200)
• Subclinical hypopigmentation of the skin and hair in a Japanese patient with Hermansky-Pudlak syndrome type 3. (PMID:31621111)
• Report of Hermansky-Pudlak Syndrome in Two Families with Novel Variants in HPS3 and HPS4 Genes. (PMID:36672886)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	hps3	ENSDARG00000015749
mus_musculus	Hps3	ENSMUSG00000027615
rattus_norvegicus	Hps3	ENSRNOG00000031406
drosophila_melanogaster	CG14562	FBGN0037142

Protein

Protein identifiers

BLOC-2 complex member HPS3 — Q969F9 (reviewed: Q969F9)

Alternative names: Hermansky-Pudlak syndrome 3 protein

All UniProt accessions (3): Q969F9, G5E9V4, H7C5G2

UniProt curated annotations — full annotation on UniProt →

Function. Involved in early stages of melanosome biogenesis and maturation.

Subunit / interactions. Component of the biogenesis of lysosome-related organelles complex-2 (or BLOC2) composed of HPS3, HPS5 and HPS6. Interacts with HPS5. Interacts with HPS6.

Subcellular location. Cytoplasm. Cytosol.

Tissue specificity. Widely expressed. Higher levels of expression are observed in kidney, liver and placenta.

Disease relevance. Hermansky-Pudlak syndrome 3 (HPS3) [MIM:614072] 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.

Isoforms (2)

UniProt ID	Names	Canonical?
Q969F9-1	1	yes
Q969F9-2	2

RefSeq proteins (2): NP_001295187, NP_115759* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR017216	HPS3	Family
IPR029437	HPS3_N	Domain
IPR029438	HPS3_C	Domain

Pfam: PF14761, PF14763

UniProt features (10 total): sequence variant 3, sequence conflict 3, splice variant 2, chain 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q969F9-F1	82.67	0.47

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 167 (showing top): chr3q24, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_VESICLE_ORGANIZATION, GOBP_CELLULAR_PIGMENTATION, GOBP_PIGMENTATION, MODULE_205, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, GOBP_SECRETORY_GRANULE_ORGANIZATION, USF_01, GOBP_PIGMENT_GRANULE_ORGANIZATION, GOBP_ORGANELLE_ASSEMBLY, LIAO_METASTASIS, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, DOUGLAS_BMI1_TARGETS_UP

GO Biological Process (3): pigmentation (GO:0043473), platelet dense granule organization (GO:0060155), melanosome assembly (GO:1903232)

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

GO Cellular Component (4): cytoplasm (GO:0005737), early endosome (GO:0005769), cytosol (GO:0005829), BLOC-2 complex (GO:0031084)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
biological_process	1
secretory granule organization	1
melanosome organization	1
organelle assembly	1
binding	1
intracellular anatomical structure	1
endosome	1
cytoplasm	1
BLOC complex	1

Protein interactions and networks

STRING

674 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HPS3	HPS5	Q9UPZ3	999
HPS3	HPS6	Q86YV9	999
HPS3	HPS4	Q9NQG7	989
HPS3	BLOC1S3	Q6QNY0	959
HPS3	BLOC1S6	Q9UL45	939
HPS3	DTNBP1	Q96EV8	926
HPS3	AP3B1	O00203	925
HPS3	LYST	Q99698	741
HPS3	TYRP1	P17643	730
HPS3	AP3D1	O14617	727
HPS3	BLOC1S5	Q8TDH9	710
HPS3	SP4	Q02446	687
HPS3	HPS1	Q92902	666
HPS3	TYR	P14679	596
HPS3	LRMDA	Q9H2I8	577

IntAct

42 interactions, top by confidence:

A	B	Type	Score
TKT	POTEF	psi-mi:“MI:0914”(association)	0.530
TCL1B	MED14	psi-mi:“MI:0914”(association)	0.530
SLC15A4	PGRMC1	psi-mi:“MI:0914”(association)	0.530
HPS6	HPS3	psi-mi:“MI:0915”(physical association)	0.500
HPS3	sifA	psi-mi:“MI:0915”(physical association)	0.470
FKBP5	IFT56	psi-mi:“MI:0914”(association)	0.350
FKBP8	GNB5	psi-mi:“MI:0914”(association)	0.350
DUSP16	MEIOC	psi-mi:“MI:0914”(association)	0.350
HPS5	TTC4	psi-mi:“MI:0914”(association)	0.350
B4GALT2	LENG9	psi-mi:“MI:0914”(association)	0.350
KLHL34	IFT56	psi-mi:“MI:0914”(association)	0.350
ATG7	IFT56	psi-mi:“MI:0914”(association)	0.350
FAM167A	IFT56	psi-mi:“MI:0914”(association)	0.350
TRMU	IFT56	psi-mi:“MI:0914”(association)	0.350
INF2	PIPSL	psi-mi:“MI:0914”(association)	0.350
D2HGDH	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
C9orf163	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
SULT1C4	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
PUDP	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
LOXL4	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
NSUN5P1		psi-mi:“MI:0914”(association)	0.350
F12		psi-mi:“MI:0914”(association)	0.350
SLC25A48	TXNDC9	psi-mi:“MI:0914”(association)	0.350
CIB2	APAF1	psi-mi:“MI:0914”(association)	0.350
PPM1M	GAK	psi-mi:“MI:0914”(association)	0.350
ZNF252P-AS1	INPP4B	psi-mi:“MI:0914”(association)	0.350
SOHLH1	FANCA	psi-mi:“MI:0914”(association)	0.350
MAP2K2	FANCA	psi-mi:“MI:0914”(association)	0.350
DHFR	FANCA	psi-mi:“MI:0914”(association)	0.350

BioGRID (52): HPS3 (Affinity Capture-RNA), HPS3 (Affinity Capture-MS), HPS3 (Affinity Capture-MS), HPS3 (Affinity Capture-MS), HPS3 (Affinity Capture-MS), HPS3 (Affinity Capture-MS), HPS3 (Affinity Capture-MS), HPS3 (Affinity Capture-MS), HPS3 (Affinity Capture-MS), HPS3 (Affinity Capture-MS), HPS3 (Affinity Capture-RNA), HPS3 (Affinity Capture-MS), HPS3 (Proximity Label-MS), HPS3 (Affinity Capture-RNA), HPS3 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2JEB6, A0JM56, B0DOB4, B0FXQ5, B1ANS9, B4F7L9, B4GQJ7, B5DHW4, B7FF06, B7FF07, B7FF08, B7FF09, B7FF12, C5IAW9, F1LW30, F1P4W9, O08747, O95185, P0DM40, Q008S8, Q18264, Q32NR9, Q3V0B4, Q402B2, Q4G0P3, Q5R4M2, Q5T0N1, Q5XI14, Q6AXU1, Q6DCF6, Q6NRS1, Q6P2C0, Q6P5D8, Q6UXZ4, Q6ZTR5, Q6ZU64, Q761X5, Q7T2Z5, Q80W93, Q86YR7

Diamond homologs: Q91VB4, Q969F9

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
HPS3	“form complex”	BLOC-2	binding
TFEB	“up-regulates quantity by expression”	HPS3	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

1114 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	87
Likely pathogenic	112
Uncertain significance	298
Likely benign	479
Benign	58

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1067906	NM_032383.5(HPS3):c.712+1G>A	Pathogenic
1068938	NM_032383.5(HPS3):c.182_198del (p.Leu61fs)	Pathogenic
1068956	NM_032383.5(HPS3):c.1508dup (p.Met503fs)	Pathogenic
1069431	NM_032383.5(HPS3):c.814_815insGA (p.Val272fs)	Pathogenic
1070227	NM_032383.5(HPS3):c.1426dup (p.Ile476fs)	Pathogenic
1070801	NM_032383.5(HPS3):c.202_203insTGTTA (p.Ala68fs)	Pathogenic
1073245	NM_032383.5(HPS3):c.26del (p.Pro9fs)	Pathogenic
1074573	NC_000003.11:g.(?148847511)(148847747_?)del	Pathogenic
1076556	NM_032383.5(HPS3):c.1169del (p.Asn390fs)	Pathogenic
1076568	NM_032383.5(HPS3):c.859del (p.Ser287fs)	Pathogenic
1323065	NM_032383.5(HPS3):c.995_996dup (p.Leu333fs)	Pathogenic
1389989	NM_032383.5(HPS3):c.1732_1736del (p.Lys578fs)	Pathogenic
1439008	NM_032383.5(HPS3):c.1003C>T (p.Gln335Ter)	Pathogenic
1449892	NM_032383.5(HPS3):c.1686C>G (p.Tyr562Ter)	Pathogenic
1451694	NM_032383.5(HPS3):c.793del (p.Ser265fs)	Pathogenic
1451809	NC_000003.11:g.(?148868376)(148873012_?)del	Pathogenic
1452133	NM_032383.5(HPS3):c.2210dup (p.Pro738fs)	Pathogenic
1452983	NM_032383.5(HPS3):c.198_211del (p.Leu67fs)	Pathogenic
1453543	NM_032383.5(HPS3):c.306_307del (p.Arg103fs)	Pathogenic
1453803	NM_032383.5(HPS3):c.2167C>T (p.Gln723Ter)	Pathogenic
1453948	NM_032383.5(HPS3):c.712+2T>A	Pathogenic
1454368	NM_032383.5(HPS3):c.728_729insA (p.Ser244fs)	Pathogenic
1458482	NC_000003.11:g.(?148863121)(148863353_?)del	Pathogenic
1460020	NM_032383.5(HPS3):c.1045_1058del (p.Pro349fs)	Pathogenic
1460261	NM_032383.5(HPS3):c.699_700del (p.Arg234fs)	Pathogenic
1916243	NM_032383.5(HPS3):c.7C>T (p.Gln3Ter)	Pathogenic
1916244	NM_032383.5(HPS3):c.319C>T (p.Arg107Ter)	Pathogenic
1916245	NM_032383.5(HPS3):c.1012G>T (p.Glu338Ter)	Pathogenic
1916246	NM_032383.5(HPS3):c.1691+1G>A	Pathogenic
1971545	NM_032383.5(HPS3):c.119dup (p.Val41fs)	Pathogenic

SpliceAI

3086 predictions. Top by Δscore:

Variant	Effect	Δscore
3:149129936:GGCTG:G	donor_gain	1.0000
3:149129937:GCTG:G	donor_gain	1.0000
3:149129937:GCTGG:G	donor_gain	1.0000
3:149129939:TGGT:T	donor_loss	1.0000
3:149129940:GGT:G	donor_loss	1.0000
3:149129941:G:A	donor_loss	1.0000
3:149129941:G:GG	donor_gain	1.0000
3:149129942:T:A	donor_loss	1.0000
3:149141185:A:AG	donor_gain	1.0000
3:149141285:A:AG	acceptor_gain	1.0000
3:149141286:A:G	acceptor_gain	1.0000
3:149141287:A:AG	acceptor_gain	1.0000
3:149141293:A:AG	acceptor_gain	1.0000
3:149141293:AGAC:A	acceptor_gain	1.0000
3:149141294:G:GA	acceptor_gain	1.0000
3:149141294:GA:G	acceptor_gain	1.0000
3:149141294:GAC:G	acceptor_gain	1.0000
3:149141294:GACG:G	acceptor_gain	1.0000
3:149141294:GACGT:G	acceptor_gain	1.0000
3:149141376:GACCG:G	donor_gain	1.0000
3:149150597:A:AG	acceptor_gain	1.0000
3:149150598:G:GT	acceptor_gain	1.0000
3:149150598:GTA:G	acceptor_gain	1.0000
3:149150598:GTAA:G	acceptor_gain	1.0000
3:149150598:GTAAC:G	acceptor_gain	1.0000
3:149150677:GAAG:G	donor_gain	1.0000
3:149150679:AGG:A	donor_loss	1.0000
3:149150681:G:C	donor_loss	1.0000
3:149150681:G:GG	donor_gain	1.0000
3:149150682:T:G	donor_loss	1.0000

AlphaMissense

6554 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:149140066:T:A	W94R	0.997
3:149140066:T:C	W94R	0.997
3:149157420:T:C	L527P	0.996
3:149157500:A:C	S554R	0.996
3:149157502:C:A	S554R	0.996
3:149157502:C:G	S554R	0.996
3:149157413:G:C	A525P	0.995
3:149157515:G:T	G559W	0.995
3:149140229:T:C	L148P	0.994
3:149157402:T:C	L521P	0.993
3:149157516:G:A	G559E	0.993
3:149158700:T:G	Y576D	0.993
3:149150607:T:C	L391P	0.992
3:149157513:T:C	L558P	0.990
3:149158703:T:G	Y577D	0.990
3:149140052:G:C	R89P	0.989
3:149145444:T:C	L354P	0.989
3:149157429:G:C	R530P	0.988
3:149163878:T:A	W840R	0.988
3:149163878:T:C	W840R	0.988
3:149129824:T:C	F34S	0.987
3:149145488:T:G	Y369D	0.987
3:149155162:T:A	W486R	0.987
3:149155162:T:C	W486R	0.987
3:149157515:G:A	G559R	0.987
3:149157515:G:C	G559R	0.987
3:149140068:G:C	W94C	0.986
3:149140068:G:T	W94C	0.986
3:149140235:T:A	V150D	0.986
3:149145438:G:A	G352D	0.986

dbSNP variants (sampled 300 via entrez): RS1000135123 (3:149139396 G>T), RS1000187403 (3:149172828 C>T), RS1000248652 (3:149165973 A>G), RS1000362201 (3:149170899 G>A), RS1000363830 (3:149166249 G>T), RS1000423568 (3:149139645 T>C), RS1000429510 (3:149158928 T>C), RS1000478093 (3:149171138 C>T), RS1000581221 (3:149167502 C>A,G,T), RS1000700749 (3:149167672 T>C), RS1000715529 (3:149165105 T>C,G), RS1000813420 (3:149172469 G>A), RS1000886705 (3:149158591 C>A), RS1000891003 (3:149153347 CTTTTG>C), RS1001006688 (3:149158603 C>T)

Disease associations

OMIM: gene MIM:606118 | disease phenotypes: MIM:614072, MIM:203300, MIM:608233

GenCC curated gene-disease

Disease	Classification	Inheritance
Hermansky-Pudlak syndrome 3	Definitive	Autosomal recessive
Hermansky-Pudlak syndrome without pulmonary fibrosis	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
Hermansky-Pudlak syndrome 3	Definitive	AR

Mondo (6): Hermansky-Pudlak syndrome 3 (MONDO:0013555), Hermansky-Pudlak syndrome (MONDO:0019312), prostate cancer (MONDO:0008315), Hermansky-Pudlak syndrome 2 (MONDO:0011997), thrombocytopenia (MONDO:0002049), Hermansky-Pudlak syndrome without pulmonary fibrosis (MONDO:0016502)

Orphanet (5): Hermansky-Pudlak syndrome due to BLOC-2 deficiency (Orphanet:231512), Hermansky-Pudlak syndrome (Orphanet:79430), Familial prostate cancer (Orphanet:1331), Hermansky-Pudlak syndrome due to AP-3 deficiency (Orphanet:183678), Hermansky-Pudlak syndrome due to AP3B1 deficiency (Orphanet:664500)

HPO phenotypes

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

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000225	Gingival bleeding
HP:0000505	Visual impairment
HP:0000565	Esotropia
HP:0000639	Nystagmus
HP:0000666	Horizontal nystagmus
HP:0000978	Bruising susceptibility
HP:0001010	Hypopigmentation of the skin
HP:0001022	Albinism
HP:0001892	Abnormal bleeding
HP:0003540	Impaired platelet aggregation
HP:0003621	Juvenile onset
HP:0004406	Spontaneous, recurrent epistaxis
HP:0005599	Hypopigmentation of hair
HP:0006934	Congenital nystagmus
HP:0007663	Reduced visual acuity
HP:0012530	Abnormal number of dense granules

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002397_82	Mean spheric corpuscular volume	4.000000e-12

MeSH disease descriptors (4)

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
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
D013921	Thrombocytopenia	C15.378.140.855; C15.378.243.937
C537709	Hermansky Pudlak syndrome 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

38 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases methylation, affects cotreatment, increases expression	7
bisphenol A	affects expression, affects cotreatment, increases abundance	2
aristolochic acid I	decreases expression	1
ginger extract	affects cotreatment, affects expression, increases abundance	1
triphenyl phosphate	affects expression	1
kojic acid	decreases expression	1
arsenite	affects binding, decreases reaction	1
potassium chromate(VI)	decreases expression, affects cotreatment	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	1
dorsomorphin	affects cotreatment, decreases expression, increases expression	1
NSC 689534	affects binding, decreases expression	1
Bortezomib	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Arsenic Trioxide	increases expression	1
Vorinostat	increases expression	1
Air Pollutants, Occupational	decreases expression	1
Arbutin	decreases expression	1
Benztropine	affects cotreatment, increases expression	1
Cadmium	decreases expression, increases abundance	1
Copper	affects binding, decreases expression	1
Cuprizone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Hydralazine	increases expression, affects cotreatment	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression	1
Nickel	decreases expression	1
Oils, Volatile	affects cotreatment, affects expression, increases abundance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer