HPS6

Summary

HPS6 (HPS6 biogenesis of lysosomal organelles complex 2 subunit 3, HGNC:18817) is a protein-coding gene on chromosome 10q24.32, encoding BLOC-2 complex member HPS6 (Q86YV9). May regulate the synthesis and function of lysosomes and of highly specialized organelles, such as melanosomes and platelet dense granules.

This intronless gene encodes a protein that may play a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. This protein interacts with Hermansky-Pudlak syndrome 5 protein. Mutations in this gene are associated with Hermansky-Pudlak syndrome type 6.

Source: NCBI Gene 79803 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Hermansky-Pudlak syndrome 6 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 611 total — 63 pathogenic, 19 likely-pathogenic
• Phenotypes (HPO): 37
• Druggable target: yes
• MANE Select transcript: NM_024747

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18817
Approved symbol	HPS6
Name	HPS6 biogenesis of lysosomal organelles complex 2 subunit 3
Location	10q24.32
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22501, BLOC2S3
Ensembl gene	ENSG00000166189
Ensembl biotype	protein_coding
OMIM	607522
Entrez	79803

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000299238

RefSeq mRNA: 1 — MANE Select: NM_024747 NM_024747

CCDS: CCDS7527

Canonical transcript exons

ENST00000299238 — 1 exons

Exon	Start	End
ENSE00001100752	102065349	102068036

Expression profiles

Bgee: expression breadth ubiquitous, 216 present calls, max score 84.39.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.6152 / max 80.8415, expressed in 1772 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
106676	7.6152	1772

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	84.39	gold quality
gingival epithelium	UBERON:0001949	82.99	silver quality
stromal cell of endometrium	CL:0002255	82.50	gold quality
mucosa of transverse colon	UBERON:0004991	82.50	gold quality
gingiva	UBERON:0001828	81.48	silver quality
leukocyte	CL:0000738	81.46	gold quality
monocyte	CL:0000576	81.19	gold quality
mononuclear cell	CL:0000842	81.09	gold quality
cerebellar vermis	UBERON:0004720	80.71	gold quality
apex of heart	UBERON:0002098	80.33	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.16	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.13	gold quality
pancreatic ductal cell	CL:0002079	79.43	silver quality
ileal mucosa	UBERON:0000331	79.35	silver quality
decidua	UBERON:0002450	79.35	gold quality
right adrenal gland	UBERON:0001233	78.99	gold quality
epithelium of esophagus	UBERON:0001976	78.92	silver quality
mammalian vulva	UBERON:0000997	78.41	silver quality
right adrenal gland cortex	UBERON:0035827	78.41	gold quality
blood	UBERON:0000178	78.40	gold quality
esophagus mucosa	UBERON:0002469	78.31	gold quality
prefrontal cortex	UBERON:0000451	78.13	gold quality
left adrenal gland	UBERON:0001234	78.05	gold quality
body of stomach	UBERON:0001161	77.97	gold quality
squamous epithelium	UBERON:0006914	77.86	silver quality
esophagus	UBERON:0001043	77.74	gold quality
muscle of leg	UBERON:0001383	77.72	gold quality
esophagus squamous epithelium	UBERON:0006920	77.71	silver quality
gastrocnemius	UBERON:0001388	77.70	gold quality
transverse colon	UBERON:0001157	77.61	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.07

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

24 targeting HPS6, 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-8485	100.00	77.57	4731
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-5689	99.50	71.26	1154
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-5190	99.15	67.76	1234
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-153-3P	98.96	72.51	1644
HSA-MIR-6847-5P	97.93	66.74	1808
HSA-MIR-1291	96.28	65.89	1224
HSA-MIR-9900	96.06	65.48	557
HSA-MIR-6775-3P	95.76	65.91	982

Literature-anchored findings (GeneRIF, showing 11)

• Component of BLOC-2. Results suggest a common biological basis underlying the pathogenesis of HPS-3, -5 and -6 disease. (PMID:15030569)
• Molecular studies showed a variety of mutations in the single exon HPS6 gene, including frame shift, missense, and nonsense mutations as well as a approximately 20 kb deletion spanning the entire HPS6 genomic region. (PMID:19843503)
• Mutation of the protein-trafficking gene Hps6 increased sensitivity of melanoma cells to cis-diaminedichloroplatinum II treatment. (PMID:22203954)
• HPS6 interacts with dynactin p150Glued to mediate retrograde trafficking and maturation of lysosomes (PMID:25189619)
• Biallelic, truncating mutations in HPS6 were identified by candidate Sanger sequencing and included a novel variant. (PMID:26823395)
• we report novel HPS6 mutations as the first report of HPS6 mutations in the Japanese population. The clinical features in the two sisters suggest OA. Although the patients in this study showed no bleeding problem, we could establish a diagnosis of HPS-6 by WES. (PMID:27225848)
• Identification of a novel mutation in HPS6 in an individual with hemophilia B shows that, although quite rare, patients may be diagnosed with two independent inherited bleeding disorders. No evidence of lung disease was found in this adult patient with Hermansky-Pudlak syndrome subtype 6 (PMID:27641950)
• the novel loss-of-function variant in the HPS6 subunit of biogenesis of lysosome-related organelles complex 2 is pathologic and leads to a reduced platelet dense granules and their release. The findings are compatible with an impaired platelet function and hence an enhanced bleeding risk. (PMID:27917594)
• we report a novel homozygous c.383 T > C missense variant in HPS6 associated with low cellular levels of HPS6 mRNA and protein in an individual with subclinical oculocutaneous albinism and a history of severe bleeding (PMID:30369044)
• Hermansky-Pudlak syndrome: Five Chinese patients with novel variants in HPS1 and HPS6. (PMID:33878481)
• Novel Variants of HPS6 Cause Suspected Ocular Albinism: A Report of 2 Cases and the Profile of HPS6 Variants. (PMID:38091959)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Hps6	ENSMUSG00000074811
rattus_norvegicus	Hps6	ENSRNOG00000077977

Protein

Protein identifiers

BLOC-2 complex member HPS6 — Q86YV9 (reviewed: Q86YV9)

Alternative names: Hermansky-Pudlak syndrome 6 protein, Ruby-eye protein homolog

All UniProt accessions (1): Q86YV9

UniProt curated annotations — full annotation on UniProt →

Function. May regulate the synthesis and function of lysosomes and of highly specialized organelles, such as melanosomes and platelet dense granules. Acts as a cargo adapter for the dynein-dynactin motor complex to mediate the transport of lysosomes from the cell periphery to the perinuclear region. Facilitates retrograde lysosomal trafficking by linking the motor complex to lysosomes, and perinuclear positioning of lysosomes is crucial for the delivery of endocytic cargos to lysosomes, for lysosome maturation and functioning.

Subunit / interactions. Component of the biogenesis of lysosome-related organelles complex-2 (or BLOC2) composed of HPS3, HPS5 and HPS6. Interacts with HPS5 and HPS3. Interacts with biogenesis of lysosome-related organelles complex-1 (BLOC1). Interacts with AP-3 complex. Interacts with MNAT1. Interacts with DCTN1 and dynein intermediate chain.

Subcellular location. Microsome membrane. Cytoplasm. Cytosol. Early endosome membrane. Lysosome membrane.

Tissue specificity. Ubiquitous.

Disease relevance. Hermansky-Pudlak syndrome 6 (HPS6) [MIM:614075] 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.

RefSeq proteins (1): NP_079023* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR017218	BLOC-2_complex_Hps6_subunit	Family
IPR046822	HPS6_C	Domain
IPR046823	HPS6_N	Domain

Pfam: PF15702, PF20468

UniProt features (1 total): chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86YV9-F1	77.54	0.12

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 177 (showing top): GOCC_VACUOLAR_MEMBRANE, GOBP_VESICLE_ORGANIZATION, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_CELLULAR_PIGMENTATION, GOMF_GTPASE_BINDING, GOBP_PIGMENTATION, GOBP_LIPID_HOMEOSTASIS, GOBP_WOUND_HEALING, GOBP_SECRETORY_GRANULE_ORGANIZATION, GOBP_SECRETION, GOBP_PIGMENT_GRANULE_ORGANIZATION, GOBP_ORGANELLE_ASSEMBLY, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_LIPID_METABOLIC_PROCESS, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN

GO Biological Process (9): lipid metabolic process (GO:0006629), blood coagulation (GO:0007596), protein secretion (GO:0009306), lysosome localization (GO:0032418), lipid homeostasis (GO:0055088), platelet dense granule organization (GO:0060155), protein localization to membrane (GO:0072657), melanosome assembly (GO:1903232), pigmentation (GO:0043473)

GO Molecular Function (3): GTP-dependent protein binding (GO:0030742), small GTPase binding (GO:0031267), protein binding (GO:0005515)

GO Cellular Component (11): nucleoplasm (GO:0005654), lysosomal membrane (GO:0005765), early endosome (GO:0005769), cytosol (GO:0005829), membrane (GO:0016020), BLOC-2 complex (GO:0031084), early endosome membrane (GO:0031901), cytoplasm (GO:0005737), lysosome (GO:0005764), endosome (GO:0005768), endoplasmic reticulum (GO:0005783)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	2
endomembrane system	2
primary metabolic process	1
hemostasis	1
wound healing	1
coagulation	1
protein transport	1
secretion by cell	1
establishment of protein localization to extracellular region	1
protein localization to extracellular region	1
vacuolar localization	1
chemical homeostasis	1
secretory granule organization	1
intracellular protein localization	1
localization within membrane	1
melanosome organization	1
organelle assembly	1
biological_process	1
protein binding	1
GTPase binding	1
binding	1
nuclear lumen	1
lysosome	1
lytic vacuole membrane	1
endosome	1
BLOC complex	1
early endosome	1
endosome membrane	1
intracellular anatomical structure	1
lytic vacuole	1
cytoplasmic vesicle	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

872 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HPS6	HPS5	Q9UPZ3	999
HPS6	HPS3	Q969F9	999
HPS6	HPS4	Q9NQG7	985
HPS6	BLOC1S6	Q9UL45	954
HPS6	BLOC1S3	Q6QNY0	951
HPS6	DTNBP1	Q96EV8	941
HPS6	AP3B1	O00203	841
HPS6	TYRP1	P17643	759
HPS6	SP4	Q02446	688
HPS6	AP3D1	O14617	683
HPS6	BLOC1S2	Q6QNY1	678
HPS6	LYST	Q99698	654
HPS6	SNAPIN	O95295	648
HPS6	BLOC1S1	P78537	639
HPS6	DCTN1	Q14203	619

IntAct

42 interactions, top by confidence:

A	B	Type	Score
DNAJC7	PLD2	psi-mi:“MI:0914”(association)	0.640
TCL1B	MED14	psi-mi:“MI:0914”(association)	0.530
BAG2	HGS	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
EP300	HPS6	psi-mi:“MI:0915”(physical association)	0.370
HPS6	OSGEP	psi-mi:“MI:0915”(physical association)	0.370
HPS6	PIK3CB	psi-mi:“MI:0915”(physical association)	0.370
HPS6	TTC19	psi-mi:“MI:0915”(physical association)	0.370
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
BVLF1	VWA8	psi-mi:“MI:0914”(association)	0.350
NS1	ESYT2	psi-mi:“MI:0914”(association)	0.350
METTL14	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
HPS6	HPS3	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
	NUDT19	psi-mi:“MI:0914”(association)	0.350
IRAK1	ILVBL	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
HPS5	TTC4	psi-mi:“MI:0914”(association)	0.350
NPAS1	CIBAR1	psi-mi:“MI:0914”(association)	0.350
HSPA8	SBNO1	psi-mi:“MI:0914”(association)	0.350
SULT1C4	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
HPS6	TUSC2	psi-mi:“MI:0914”(association)	0.350
HPS5	BAG2	psi-mi:“MI:0914”(association)	0.350
AFG2A	ESYT2	psi-mi:“MI:0914”(association)	0.350
DNAJA2	ENC1	psi-mi:“MI:0914”(association)	0.350
SLC22A11	CNOT1	psi-mi:“MI:0914”(association)	0.350
SLC27A6	NBAS	psi-mi:“MI:0914”(association)	0.350
SLC30A6	PSMD14	psi-mi:“MI:0914”(association)	0.350
SLC35E4	XPO1	psi-mi:“MI:0914”(association)	0.350

BioGRID (51): HPS6 (Affinity Capture-MS), HPS6 (Affinity Capture-MS), HPS5 (Affinity Capture-MS), HPS3 (Affinity Capture-MS), HPS6 (Affinity Capture-MS), HPS6 (Affinity Capture-MS), HPS6 (Affinity Capture-MS), HPS6 (Affinity Capture-RNA), HPS6 (Affinity Capture-MS), HPS6 (Two-hybrid), HPS6 (Affinity Capture-MS), HPS6 (Affinity Capture-MS), HPS6 (Affinity Capture-MS), HPS6 (Affinity Capture-MS), HPS6 (Reconstituted Complex)

ESM2 similar proteins: A0JN53, A1L3T7, A6NE52, D3ZVB0, D4A929, G3MZC5, O15287, O43299, O75064, P29474, P46062, P49000, P58660, Q0P5G1, Q15572, Q2VPB7, Q3TAP4, Q3U1Y4, Q3UPH7, Q562E7, Q5JYT7, Q5ND34, Q5XIS1, Q6P773, Q6PDZ2, Q6ZNJ1, Q6ZPG2, Q6ZQA0, Q6ZQQ6, Q6ZS72, Q76MJ5, Q7M733, Q7Z3H0, Q80TE0, Q86YV9, Q8BLY7, Q8C2K5, Q8C7B8, Q8CIE4, Q8K330

Diamond homologs: Q7M733, Q86YV9, Q8BLY7

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
HPS6	“form complex”	BLOC-2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 62 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.

GO biological processes:

GO term	Partners	Fold	FDR
response to ethanol	5	13.8×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	63
Likely pathogenic	19
Uncertain significance	295
Likely benign	174
Benign	6

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1050563	NM_024747.6(HPS6):c.206_210dup (p.Trp71fs)	Pathogenic
1210214	NM_024747.6(HPS6):c.1030G>T (p.Glu344Ter)	Pathogenic
1323067	NM_024747.6(HPS6):c.1411C>T (p.Gln471Ter)	Pathogenic
1368527	NM_024747.6(HPS6):c.1114C>T (p.Arg372Ter)	Pathogenic
1452276	NM_024747.6(HPS6):c.60_64dup (p.Leu22fs)	Pathogenic
1459302	NC_000010.10:g.(?103825232)(103827559_?)del	Pathogenic
1691238	NM_024747.6(HPS6):c.1228_1252del (p.Tyr410fs)	Pathogenic
2012303	NM_024747.6(HPS6):c.1708C>T (p.Gln570Ter)	Pathogenic
2016481	NM_024747.6(HPS6):c.355G>T (p.Glu119Ter)	Pathogenic
2062597	NM_024747.6(HPS6):c.181C>T (p.Arg61Ter)	Pathogenic
2100988	NM_024747.6(HPS6):c.1612C>T (p.Gln538Ter)	Pathogenic
2178860	NM_024747.6(HPS6):c.1149_1150del (p.Phe384fs)	Pathogenic
2418963	NM_024747.6(HPS6):c.503_504del (p.Leu168fs)	Pathogenic
2699694	NM_024747.6(HPS6):c.407_429del (p.Gly136fs)	Pathogenic
2702141	NM_024747.6(HPS6):c.627G>A (p.Trp209Ter)	Pathogenic
2713019	NM_024747.6(HPS6):c.860del (p.Gly287fs)	Pathogenic
2751605	NM_024747.6(HPS6):c.894dup (p.Arg299fs)	Pathogenic
2772886	NM_024747.6(HPS6):c.657G>A (p.Trp219Ter)	Pathogenic
2775573	NM_024747.6(HPS6):c.139_148del (p.Arg47fs)	Pathogenic
2794877	NM_024747.6(HPS6):c.471del (p.Ala158fs)	Pathogenic
2797868	NM_024747.6(HPS6):c.1147_1148del (p.Leu383fs)	Pathogenic
2803492	NM_024747.6(HPS6):c.441_453del (p.Ala148fs)	Pathogenic
2824592	NM_024747.6(HPS6):c.89C>G (p.Ser30Ter)	Pathogenic
2826292	NM_024747.6(HPS6):c.651_655del (p.Ile218fs)	Pathogenic
2831614	NM_024747.6(HPS6):c.1573del (p.Leu525fs)	Pathogenic
2837145	NM_024747.6(HPS6):c.87_108dup (p.Ser37fs)	Pathogenic
2841763	NM_024747.6(HPS6):c.604del (p.Leu202fs)	Pathogenic
2842896	NM_024747.6(HPS6):c.1743del (p.Phe583fs)	Pathogenic
2845408	NM_024747.6(HPS6):c.1553G>A (p.Trp518Ter)	Pathogenic
2852241	NM_024747.6(HPS6):c.1403dup (p.Lys469fs)	Pathogenic

SpliceAI

84 predictions. Top by Δscore:

Variant	Effect	Δscore
10:102065569:TCC:T	donor_gain	0.9300
10:102065508:GACC:G	donor_gain	0.8200
10:102065543:G:GT	donor_gain	0.7000
10:102065629:T:TA	donor_gain	0.6400
10:102065630:A:AA	donor_gain	0.6400
10:102065552:G:GA	donor_gain	0.6300
10:102065764:A:T	donor_gain	0.6300
10:102065551:T:TA	donor_gain	0.6000
10:102065580:GGC:G	donor_gain	0.6000
10:102065589:G:GT	donor_gain	0.5800
10:102066939:G:GT	donor_gain	0.5800
10:102065477:G:GT	donor_gain	0.5600
10:102065570:C:A	donor_gain	0.5600
10:102065576:C:A	donor_gain	0.5600
10:102065574:G:GG	donor_gain	0.5200
10:102066687:G:GC	acceptor_gain	0.4600
10:102065573:A:AG	donor_gain	0.4500
10:102065566:C:CA	donor_gain	0.4400
10:102065565:GCG:G	donor_gain	0.4200
10:102065564:AGC:A	donor_gain	0.4100
10:102065758:TGTGG:T	donor_gain	0.4100
10:102065759:GTGGG:G	donor_gain	0.4100
10:102065640:C:G	donor_gain	0.3900
10:102066631:T:TA	acceptor_gain	0.3900
10:102066140:C:T	donor_gain	0.3800
10:102065583:A:AG	donor_gain	0.3700
10:102065584:G:GG	donor_gain	0.3700
10:102065760:TGGGA:T	donor_gain	0.3700
10:102065761:GGGAG:G	donor_gain	0.3700
10:102066187:G:GG	donor_gain	0.3700

AlphaMissense

4817 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:102067104:T:A	W544R	0.990
10:102067104:T:C	W544R	0.990
10:102066624:T:C	F384L	0.979
10:102066626:T:A	F384L	0.979
10:102066626:T:G	F384L	0.979
10:102067179:T:C	C569R	0.979
10:102067106:G:C	W544C	0.978
10:102067106:G:T	W544C	0.978
10:102067297:C:A	A608D	0.978
10:102066881:G:C	K469N	0.977
10:102066881:G:T	K469N	0.977
10:102067167:T:C	F565L	0.977
10:102067169:T:A	F565L	0.977
10:102067169:T:G	F565L	0.977
10:102067222:T:C	F583S	0.977
10:102067351:T:C	L626P	0.976
10:102067389:G:C	A639P	0.975
10:102067419:T:A	W649R	0.975
10:102067419:T:C	W649R	0.975
10:102066448:C:A	A325D	0.974
10:102066693:G:C	A407P	0.973
10:102067213:T:C	L580P	0.970
10:102067393:T:A	V640D	0.970
10:102066469:T:C	L332S	0.969
10:102067168:T:G	F565C	0.969
10:102065892:T:A	W140R	0.968
10:102065892:T:C	W140R	0.968
10:102067351:T:A	L626Q	0.967
10:102065583:A:C	S37R	0.966
10:102065585:T:A	S37R	0.966

dbSNP variants (sampled 300 via entrez): RS1000394135 (10:102064465 C>T), RS1000690587 (10:102063959 A>C), RS1001722720 (10:102064996 G>A), RS1001775314 (10:102064794 T>C), RS1002519784 (10:102063587 G>A), RS1003468935 (10:102065422 G>A,C), RS1003604981 (10:102065282 C>A,T), RS1005391727 (10:102065444 A>G,T), RS1006089495 (10:102065616 C>A), RS1006808165 (10:102064441 C>A,T), RS1007197875 (10:102068115 T>C,G), RS1007468130 (10:102068327 C>G), RS1008413444 (10:102065386 C>A,T), RS1008632314 (10:102064040 AAAAAT>A,AAAAATAAAAT,AAAAATAAAATAAAAT), RS1009403211 (10:102063591 T>C)

Disease associations

OMIM: gene MIM:607522 | disease phenotypes: MIM:614075, MIM:203300, MIM:185050

GenCC curated gene-disease

Disease	Classification	Inheritance
Hermansky-Pudlak syndrome 6	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 6	Definitive	AR

Mondo (4): Hermansky-Pudlak syndrome 6 (MONDO:0013558), Hermansky-Pudlak syndrome (MONDO:0019312), platelet storage pool deficiency (MONDO:0008495), Hermansky-Pudlak syndrome without pulmonary fibrosis (MONDO:0016502)

Orphanet (3): Hermansky-Pudlak syndrome due to BLOC-2 deficiency (Orphanet:231512), Hermansky-Pudlak syndrome (Orphanet:79430), Alpha delta granule deficiency (Orphanet:734)

HPO phenotypes

37 total (30 of 37 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000011	Neurogenic bladder
HP:0000020	Urinary incontinence
HP:0000365	Hearing impairment
HP:0000421	Epistaxis
HP:0000486	Strabismus
HP:0000613	Photophobia
HP:0000639	Nystagmus
HP:0000646	Amblyopia
HP:0000666	Horizontal nystagmus
HP:0000978	Bruising susceptibility
HP:0001010	Hypopigmentation of the skin
HP:0001022	Albinism
HP:0001104	Macular hypoplasia
HP:0001107	Ocular albinism
HP:0001195	Single umbilical artery
HP:0001263	Global developmental delay
HP:0001583	Rotary nystagmus
HP:0002023	Anal atresia
HP:0002206	Pulmonary fibrosis
HP:0002607	Bowel incontinence
HP:0002788	Recurrent upper respiratory tract infections
HP:0003010	Prolonged bleeding time
HP:0003577	Congenital onset
HP:0003593	Infantile onset
HP:0004866	Impaired ADP-induced platelet aggregation
HP:0004871	Perineal fistula
HP:0007443	Partial albinism
HP:0007663	Reduced visual acuity

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005316_73	Intelligence (MTAG)	2.000000e-09
GCST009524_304	Household income (MTAG)	1.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0009695	household income

MeSH disease descriptors (2)

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
D010981	Platelet Storage Pool Deficiency	C15.378.100.685; C15.378.140.735; C15.378.463.735

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295884 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression	2
Cadmium Chloride	decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	decreases expression	1
methylmercuric chloride	decreases expression	1
methylparaben	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
ferrous chloride	decreases expression	1
butylparaben	increases expression	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
chloropicrin	decreases expression	1
ICG 001	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Leflunomide	decreases expression	1
Atrazine	decreases expression	1
Benzene	increases expression	1
Cadmium	decreases expression	1
Cannabidiol	decreases expression	1
Cisplatin	increases expression, affects cotreatment	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Ivermectin	decreases expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, decreases expression, increases abundance	1
Potassium Chloride	decreases expression, decreases response to substance	1
Dronabinol	decreases expression, decreases response to substance	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118990	Binding	Binding affinity to HPS6 in human NCI-H358 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_0R46	GM17881	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04193592	PHASE2	UNKNOWN	Efficacy and Safety of Pirfenidone Treatment in HPS-ILD
NCT00001596	PHASE2	COMPLETED	Oral Pirfenidone for the Pulmonary Fibrosis of Hermansky-Pudlak Syndrome
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
NCT05529394	Not specified	UNKNOWN	Effect of Storage Condition on CD47 Expression Level in Platelet Concentrate