HPS5

Summary

HPS5 (HPS5 biogenesis of lysosomal organelles complex 2 subunit 2, HGNC:17022) is a protein-coding gene on chromosome 11p15.1, encoding BLOC-2 complex member HPS5 (Q9UPZ3). May regulate the synthesis and function of lysosomes and of highly specialized organelles, such as melanosomes and platelet dense granules.

This 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 6 protein and may interact with the cytoplasmic domain of integrin, alpha-3. Mutations in this gene are associated with Hermansky-Pudlak syndrome type 5. Multiple transcript variants encoding two distinct isoforms have been identified for this gene.

Source: NCBI Gene 11234 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Hermansky-Pudlak syndrome 5 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 8
• Clinical variants (ClinVar): 1,175 total — 91 pathogenic, 37 likely-pathogenic
• Phenotypes (HPO): 20
• MANE Select transcript: NM_181507

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17022
Approved symbol	HPS5
Name	HPS5 biogenesis of lysosomal organelles complex 2 subunit 2
Location	11p15.1
Locus type	gene with protein product
Status	Approved
Aliases	BLOC2S2, AIBP63, RU2
Ensembl gene	ENSG00000110756
Ensembl biotype	protein_coding
OMIM	607521
Entrez	11234

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 11 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000349215, ENST00000352460, ENST00000396253, ENST00000399287, ENST00000438420, ENST00000531848, ENST00000537258, ENST00000543728, ENST00000544218, ENST00000545561, ENST00000589545, ENST00000868347, ENST00000868348, ENST00000868349, ENST00000923628, ENST00000943365

RefSeq mRNA: 3 — MANE Select: NM_181507 NM_007216, NM_181507, NM_181508

CCDS: CCDS7836, CCDS7837

Canonical transcript exons

ENST00000349215 — 23 exons

Exon	Start	End
ENSE00000705611	18295999	18296122
ENSE00000705614	18296798	18296984
ENSE00000886573	18300828	18300916
ENSE00000886574	18305422	18305493
ENSE00001106643	18297559	18297717
ENSE00001106650	18308946	18309079
ENSE00001106654	18306135	18306347
ENSE00001106670	18298792	18298970
ENSE00001150970	18281950	18282220
ENSE00003458757	18285346	18285459
ENSE00003472510	18292899	18292976
ENSE00003485075	18311387	18311451
ENSE00003485787	18310741	18310933
ENSE00003492623	18287893	18288013
ENSE00003554355	18311914	18312024
ENSE00003564511	18295020	18295169
ENSE00003575642	18317751	18317907
ENSE00003582118	18291442	18292019
ENSE00003583850	18287535	18287690
ENSE00003627456	18286591	18286710
ENSE00003655944	18283795	18283901
ENSE00003896368	18321946	18322140
ENSE00003896533	18278676	18279942

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 93.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.0948 / max 1199.1351, expressed in 1783 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
118930	11.0170	1751
118931	1.1010	750
118932	0.4912	178
118929	0.3568	167
118928	0.0988	21
118927	0.0300	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	93.20	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.50	gold quality
liver	UBERON:0002107	89.43	gold quality
corpus callosum	UBERON:0002336	88.60	gold quality
adrenal tissue	UBERON:0018303	88.36	gold quality
tonsil	UBERON:0002372	88.06	gold quality
right lobe of liver	UBERON:0001114	88.04	gold quality
tibial nerve	UBERON:0001323	87.01	gold quality
lymph node	UBERON:0000029	86.89	gold quality
calcaneal tendon	UBERON:0003701	86.86	gold quality
saliva-secreting gland	UBERON:0001044	86.64	gold quality
minor salivary gland	UBERON:0001830	86.62	gold quality
bone marrow cell	CL:0002092	86.29	gold quality
right testis	UBERON:0004534	86.02	gold quality
testis	UBERON:0000473	85.86	gold quality
placenta	UBERON:0001987	85.85	gold quality
thoracic aorta	UBERON:0001515	85.52	gold quality
ascending aorta	UBERON:0001496	85.46	gold quality
left testis	UBERON:0004533	85.10	gold quality
monocyte	CL:0000576	84.62	gold quality
leukocyte	CL:0000738	84.54	gold quality
descending thoracic aorta	UBERON:0002345	84.54	gold quality
vermiform appendix	UBERON:0001154	84.00	gold quality
right coronary artery	UBERON:0001625	83.97	gold quality
left coronary artery	UBERON:0001626	83.95	gold quality
duodenum	UBERON:0002114	83.78	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.75	gold quality
colonic epithelium	UBERON:0000397	83.72	gold quality
islet of Langerhans	UBERON:0000006	83.67	gold quality
endometrium	UBERON:0001295	83.49	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CUX1, NFYA, RARB

miRNA regulators (miRDB)

67 targeting HPS5, 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-126-5P	100.00	72.71	3180
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-609	99.82	64.26	505
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712

Literature-anchored findings (GeneRIF, showing 7)

• Component of BLOC-2. Results suggest a common biological basis underlying the pathogenesis of HPS-3, -5 and -6 disease. (PMID:15030569)
• LAMP-3 distribution was restricted to the perinuclear region in HPS-5 fibroblasts, instead of extending to the periphery (PMID:15296495)
• Tyrosinase and TYRP1 are mistrafficked, however, and fail to be efficiently delivered to melanosomes of HPS-5 melanocytes (PMID:17301833)
• Seven mutations (six previously unreported) were described in the HPS1, HPS4, and HPS5 genes among Hermansky-Pudlak Syndrome patients of Mexican, Uruguayan, Honduran, Cuban, Venezuelan, and Salvadoran ancestries. (PMID:21833017)
• We report a 92-year-old man with HPS 5 who, to our knowledge, is the oldest patient with HPS documented in the literature. (PMID:23607980)
• HPS5 mutation is associated with high hypopigmentation in Hermansky-Pudlak syndrome. (PMID:27593200)
• This case underscores the importance of recognizing the mild clinical phenotype of HPS-5 and utilization of both laboratory and molecular testing for diagnosis, prognostication, and surveillance for end organ damage in patients affected with HPS. (PMID:29090612)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	hps5	ENSDARG00000071062
		ENSDARG00000104040
		ENSDARG00000114424
mus_musculus	Hps5	ENSMUSG00000014418
rattus_norvegicus	Hps5	ENSRNOG00000055531
drosophila_melanogaster	p	FBGN0086679

Paralogs (1): TECPR2 (ENSG00000196663)

Protein

Protein identifiers

BLOC-2 complex member HPS5 — Q9UPZ3 (reviewed: Q9UPZ3)

Alternative names: Alpha-integrin-binding protein 63, Hermansky-Pudlak syndrome 5 protein, Ruby-eye protein 2 homolog

All UniProt accessions (4): Q9UPZ3, F5GWM5, F5H6Q8, G3V159

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. Regulates intracellular vesicular trafficking in fibroblasts. May be involved in the regulation of general functions of integrins.

Subunit / interactions. Component of the biogenesis of lysosome-related organelles complex-2 (or BLOC2) composed of HPS3, HPS5 and HPS6. Interacts with HPS6. Interacts with HPS3. May interact with all alpha-integrin chains that have an aromatic residue before the first lysine of the conserved KXGFFKR motif, including ITGA2, ITGA3, ITGA5 and ITGA6.

Subcellular location. Cytoplasm. Cytosol.

Tissue specificity. Widely expressed. Isoform 1:Highly expressed in lungs and testis. Isoform 2:Highly expressed in placenta, kidney, testis ovary, lung and thymus.

Disease relevance. Hermansky-Pudlak syndrome 5 (HPS5) [MIM:614074] 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 HPS5 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UPZ3-1	1	yes
Q9UPZ3-2	2

RefSeq proteins (3): NP_009147, NP_852608, NP_852609 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR035431	HPS5	Family
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR056445	TPR_HPS5	Domain
IPR056499	Beta-prop_HPS5-like	Domain

Pfam: PF23756, PF23758

UniProt features (14 total): sequence variant 3, sequence conflict 3, modified residue 3, region of interest 2, chain 1, compositionally biased region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UPZ3-F1	73.21	0.33

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 (3): 532, 534, 695

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 216 (showing top): BOYAULT_LIVER_CANCER_SUBCLASS_G56_DN, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_VESICLE_ORGANIZATION, AAGCCAT_MIR135A_MIR135B, MAZ_Q6, GOBP_CELLULAR_PIGMENTATION, GOBP_PIGMENTATION, GOBP_WOUND_HEALING, GOBP_SECRETORY_GRANULE_ORGANIZATION, USF_01, GOBP_PIGMENT_GRANULE_ORGANIZATION, GOBP_ORGANELLE_ASSEMBLY, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, SCHLOSSER_SERUM_RESPONSE_DN, GOBP_DEVELOPMENTAL_PIGMENTATION

GO Biological Process (5): blood coagulation (GO:0007596), developmental pigmentation (GO:0048066), platelet dense granule organization (GO:0060155), melanosome assembly (GO:1903232), pigmentation (GO:0043473)

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
hemostasis	1
wound healing	1
coagulation	1
pigmentation	1
secretory granule organization	1
melanosome organization	1
organelle assembly	1
biological_process	1
binding	1
intracellular anatomical structure	1
endosome	1
cytoplasm	1
BLOC complex	1

Protein interactions and networks

STRING

567 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HPS5	HPS6	Q86YV9	999
HPS5	HPS3	Q969F9	999
HPS5	HPS4	Q9NQG7	974
HPS5	BLOC1S6	Q9UL45	953
HPS5	BLOC1S3	Q6QNY0	950
HPS5	DTNBP1	Q96EV8	947
HPS5	AP3B1	O00203	825
HPS5	LYST	Q99698	746
HPS5	TYRP1	P17643	720
HPS5	AP3D1	O14617	706
HPS5	SP4	Q02446	689
HPS5	FRMD7	Q6ZUT3	626
HPS5	BLOC1S5	Q8TDH9	599
HPS5	LRMDA	Q9H2I8	591
HPS5	SNAPIN	O95295	575

IntAct

37 interactions, top by confidence:

A	B	Type	Score
TCL1B	MED14	psi-mi:“MI:0914”(association)	0.530
HPS5	sifA	psi-mi:“MI:0915”(physical association)	0.520
HPS5	SAP18	psi-mi:“MI:0915”(physical association)	0.400
	FER1L5	psi-mi:“MI:0915”(physical association)	0.400
Ppp2r1a	CCHCR1	psi-mi:“MI:0914”(association)	0.350
Lck	TLE5	psi-mi:“MI:0914”(association)	0.350
CEP43	CCHCR1	psi-mi:“MI:0914”(association)	0.350
CSNK2A2	WDR46	psi-mi:“MI:0914”(association)	0.350
Rassf1	TTC31	psi-mi:“MI:0914”(association)	0.350
BUB1	RBPMS	psi-mi:“MI:0914”(association)	0.350
SMC6	IFT88	psi-mi:“MI:0914”(association)	0.350
Magoh	TRAPPC13	psi-mi:“MI:0914”(association)	0.350
BLM	MCM3AP	psi-mi:“MI:0914”(association)	0.350
PHKG2	PEX10	psi-mi:“MI:0914”(association)	0.350
DLST		psi-mi:“MI:0914”(association)	0.350
AARSD1	APAF1	psi-mi:“MI:0914”(association)	0.350
GATD1		psi-mi:“MI:0914”(association)	0.350
DEF8	DPYSL4	psi-mi:“MI:0914”(association)	0.350
HPS6	HPS3	psi-mi:“MI:0914”(association)	0.350
SH2D3C	TMEM14DP	psi-mi:“MI:0914”(association)	0.350
DUSP16	MEIOC	psi-mi:“MI:0914”(association)	0.350
DNAJA2	DENND11	psi-mi:“MI:0914”(association)	0.350
GATD1	MYO9A	psi-mi:“MI:0914”(association)	0.350
SKP1	BHLHE40	psi-mi:“MI:0914”(association)	0.350
AARSD1	MAP3K7	psi-mi:“MI:0914”(association)	0.350
HPS5	TTC4	psi-mi:“MI:0914”(association)	0.350

BioGRID (60): HPS5 (Affinity Capture-MS), HPS5 (Affinity Capture-MS), HPS5 (Affinity Capture-MS), HPS5 (Affinity Capture-MS), HPS5 (Affinity Capture-MS), HPS5 (Affinity Capture-MS), HPS5 (Affinity Capture-MS), HPS5 (Affinity Capture-MS), HPS5 (Affinity Capture-MS), HPS5 (Affinity Capture-MS), HPS5 (Affinity Capture-MS), HPS5 (Affinity Capture-MS), HPS5 (Affinity Capture-MS), HPS5 (Affinity Capture-MS), HPS5 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8GXY4, A4D1P6, A8XSV3, B0JZ65, B0R160, B0WYR6, E9Q7R9, F1REV3, F6S215, O00443, O65418, P50748, Q09178, Q12769, Q17I16, Q19317, Q2TAW0, Q3MHH2, Q402B2, Q4V9P9, Q5R6T6, Q5RAY1, Q5RB52, Q5RE88, Q5ZJY3, Q5ZL79, Q5ZLL7, Q6DTM3, Q6GM71, Q6INI5, Q6P996, Q6X9E4, Q6ZQQ6, Q7TMQ7, Q86XI2, Q8BJW5, Q8BMQ2, Q8C3Y4, Q8K3E5, Q8N157

Diamond homologs: O15040, P59438, Q297N8, Q9UPZ3, Q9VHN9, Q5TU55

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
HPS5	“form complex”	BLOC-2	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

1175 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	91
Likely pathogenic	37
Uncertain significance	386
Likely benign	499
Benign	92

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1068461	NM_181507.2(HPS5):c.1831C>T (p.Gln611Ter)	Pathogenic
1070992	NM_181507.2(HPS5):c.2681T>G (p.Leu894Ter)	Pathogenic
1072840	NM_181507.2(HPS5):c.1960A>T (p.Lys654Ter)	Pathogenic
1191090	NM_181507.2(HPS5):c.220-1G>T	Pathogenic
1409362	NM_181507.2(HPS5):c.1616_1617del (p.Leu539fs)	Pathogenic
1455836	NM_181507.2(HPS5):c.1487_1488dup (p.Cys497fs)	Pathogenic
1458721	NM_181507.2(HPS5):c.3063G>A (p.Trp1021Ter)	Pathogenic
1695385	NM_181507.2(HPS5):c.370C>T (p.Arg124Ter)	Pathogenic
1931068	NM_181507.2(HPS5):c.2232T>A (p.Cys744Ter)	Pathogenic
1995536	NM_181507.2(HPS5):c.2718-2A>T	Pathogenic
2014688	NM_181507.2(HPS5):c.1447G>T (p.Glu483Ter)	Pathogenic
2016192	NM_181507.2(HPS5):c.586C>T (p.Arg196Ter)	Pathogenic
2043667	NM_181507.2(HPS5):c.220-2A>G	Pathogenic
2137025	NM_181507.2(HPS5):c.1634+1G>A	Pathogenic
21818	NM_181507.2(HPS5):c.2593C>T (p.Arg865Ter)	Pathogenic
21819	NM_181507.2(HPS5):c.2624del (p.Leu875fs)	Pathogenic
21820	NM_181507.2(HPS5):c.2928_2929dup (p.Thr977fs)	Pathogenic
21822	NM_181507.2(HPS5):c.879dup (p.Lys294fs)	Pathogenic
2693933	NM_181507.2(HPS5):c.666_674delinsCATACTTGCATAATTGTTTTTTTGACTTGGGATTTTAAGTTGAAAGGTGCAACAATTTGGCTAAACTTAGAAACCACTGGAATGTTTAAGAACTTAACATTTATTATATTTAAAACTTAGTCCCAGTTGCTCTGGAGGCTGAAGTGGGAGGATTGCTTGAGCCGGAGTTAGAGGCTGCAGTGAGCCATGATCTGTGCCACTACACTCCAGCCTCATATTTTAAAAATAAAAAAGCTGATGATGTTGTGGAAAGTCCTCAAATAGCCCAAGTATCGAGACCATCCTGGATAACACGGTGAAACCCCGTCTCTACTAAAAATACAAAAAAAATTAGCTGGGCGTGGTGACGGGCGCCTGTAGTCCCAGCTACTCGGGAGGCTGAGGCAGGAGAATGGCGTGAACCCGGGAGGCGCAGCTTGCAGTGAGCCGAGATTGCGCCACTGCACTCCAGCCTGGGCGACAGAGTGAGACTCTGTCTCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAGAAATAAATAAGAAAGACCTGAACCAGGACAGGGAAAAACAGCTAATGGAATTTATGAAGCAGGTTGACCT (p.Phe223_Pro225delinsIleLeuAlaTer)	Pathogenic
2696387	NM_181507.2(HPS5):c.1733C>G (p.Ser578Ter)	Pathogenic
2696417	NM_181507.2(HPS5):c.251T>G (p.Leu84Ter)	Pathogenic
2705746	NM_181507.2(HPS5):c.2713C>T (p.Gln905Ter)	Pathogenic
2706831	NM_181507.2(HPS5):c.2415G>A (p.Trp805Ter)	Pathogenic
2707427	NM_181507.2(HPS5):c.1109G>A (p.Trp370Ter)	Pathogenic
2735562	NM_181507.2(HPS5):c.888dup (p.His297fs)	Pathogenic
2735563	NM_181507.2(HPS5):c.302_305del (p.Val101fs)	Pathogenic
2736411	NM_181507.2(HPS5):c.1783G>T (p.Glu595Ter)	Pathogenic
2736597	NM_181507.2(HPS5):c.82dup (p.Leu28fs)	Pathogenic
2744093	NM_181507.2(HPS5):c.2949_2950insTA (p.Gly984Ter)	Pathogenic
2747149	NM_181507.2(HPS5):c.1237del (p.Asp412_Leu413insTer)	Pathogenic

SpliceAI

3756 predictions. Top by Δscore:

Variant	Effect	Δscore
11:18283914:C:CT	acceptor_gain	1.0000
11:18283915:G:T	acceptor_gain	1.0000
11:18283919:T:C	acceptor_gain	1.0000
11:18283919:T:TC	acceptor_gain	1.0000
11:18285342:TTA:T	donor_loss	1.0000
11:18285343:TACC:T	donor_loss	1.0000
11:18285344:A:AC	donor_gain	1.0000
11:18285344:AC:A	donor_gain	1.0000
11:18285345:C:CA	donor_loss	1.0000
11:18285345:C:CC	donor_gain	1.0000
11:18285345:CC:C	donor_gain	1.0000
11:18285345:CCCA:C	donor_gain	1.0000
11:18287525:T:A	donor_gain	1.0000
11:18287534:CCG:C	donor_gain	1.0000
11:18287886:AACTT:A	donor_loss	1.0000
11:18287887:ACTTA:A	donor_loss	1.0000
11:18287888:CTT:C	donor_loss	1.0000
11:18287889:TTA:T	donor_loss	1.0000
11:18287890:TA:T	donor_loss	1.0000
11:18287891:A:AC	donor_gain	1.0000
11:18287891:A:AG	donor_loss	1.0000
11:18287892:C:CC	donor_gain	1.0000
11:18292897:A:AC	donor_gain	1.0000
11:18292898:C:CC	donor_gain	1.0000
11:18292898:CA:C	donor_gain	1.0000
11:18292898:CATTG:C	donor_gain	1.0000
11:18295018:A:AC	donor_gain	1.0000
11:18295019:C:CC	donor_gain	1.0000
11:18295019:CT:C	donor_gain	1.0000
11:18295168:CA:C	acceptor_gain	1.0000

AlphaMissense

7423 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:18306221:C:A	W246C	0.999
11:18306221:C:G	W246C	0.999
11:18306223:A:G	W246R	0.999
11:18306223:A:T	W246R	0.999
11:18306227:C:A	R244S	0.998
11:18306227:C:G	R244S	0.998
11:18306228:C:G	R244T	0.998
11:18297586:G:C	S432R	0.997
11:18297586:G:T	S432R	0.997
11:18297588:T:G	S432R	0.997
11:18306228:C:A	R244M	0.997
11:18296950:C:G	R453P	0.996
11:18297583:A:C	S433R	0.996
11:18297583:A:T	S433R	0.996
11:18297585:T:G	S433R	0.996
11:18306222:C:G	W246S	0.996
11:18306314:T:A	R215S	0.996
11:18306314:T:G	R215S	0.996
11:18306327:C:T	G211E	0.996
11:18310827:A:G	W131R	0.996
11:18310827:A:T	W131R	0.996
11:18311399:G:T	A91D	0.996
11:18306180:A:G	F260S	0.995
11:18306243:G:T	A239D	0.995
11:18308988:A:G	L190P	0.995
11:18308991:A:G	L189P	0.995
11:18296979:A:C	S443R	0.994
11:18296979:A:T	S443R	0.994
11:18296981:T:G	S443R	0.994
11:18306198:A:T	V254D	0.994

dbSNP variants (sampled 300 via entrez): RS1000081928 (11:18318368 G>A), RS1000110856 (11:18322076 C>T), RS1000185204 (11:18280764 T>C), RS1000190934 (11:18323166 C>A,T), RS1000283434 (11:18282316 C>T), RS1000319484 (11:18280502 G>T), RS1000346016 (11:18324065 T>G), RS1000362908 (11:18301823 AATAAT>A), RS1000490514 (11:18294832 A>G,T), RS1000603912 (11:18301259 T>C), RS1000779209 (11:18323763 C>T), RS1000796998 (11:18307305 T>A), RS1000850180 (11:18306656 A>C), RS1000890708 (11:18307082 T>C), RS1000968916 (11:18319927 G>A,T)

Disease associations

OMIM: gene MIM:607521 | disease phenotypes: MIM:614074, MIM:203300

GenCC curated gene-disease

Disease	Classification	Inheritance
Hermansky-Pudlak syndrome 5	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 5	Definitive	AR

Mondo (4): Hermansky-Pudlak syndrome 5 (MONDO:0013557), Hermansky-Pudlak syndrome (MONDO:0019312), thrombocytopenia (MONDO:0002049), Hermansky-Pudlak syndrome without pulmonary fibrosis (MONDO:0016502)

Orphanet (2): Hermansky-Pudlak syndrome due to BLOC-2 deficiency (Orphanet:231512), Hermansky-Pudlak syndrome (Orphanet:79430)

HPO phenotypes

20 total (20 of 20 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000132	Menorrhagia
HP:0000421	Epistaxis
HP:0000486	Strabismus
HP:0000639	Nystagmus
HP:0000666	Horizontal nystagmus
HP:0000978	Bruising susceptibility
HP:0001022	Albinism
HP:0001107	Ocular albinism
HP:0001873	Thrombocytopenia
HP:0003010	Prolonged bleeding time
HP:0003593	Infantile onset
HP:0003621	Juvenile onset
HP:0003623	Neonatal onset
HP:0004866	Impaired ADP-induced platelet aggregation
HP:0007663	Reduced visual acuity
HP:0007750	Hypoplasia of the fovea
HP:0012805	Iris transillumination defect
HP:0033263	Absent platelet dense granules
HP:0100608	Metrorrhagia

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST000876_1	Amyloid A serum levels	2.000000e-51
GCST000876_4	Amyloid A serum levels	3.000000e-111
GCST001217_29	Metabolic traits	1.000000e-20
GCST004485_44	Survival in pancreatic cancer	9.000000e-06
GCST006249_20	Serum metabolite levels	3.000000e-16
GCST010244_202	Triglyceride levels	1.000000e-08
GCST012164_4	Adiponectin levels	2.000000e-06
GCST012168_6	Adiponectin levels	9.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004725	metabolite measurement
EFO:0000638	overall survival
EFO:0004530	triglyceride measurement
EFO:0004502	adiponectin measurement

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
D013921	Thrombocytopenia	C15.378.140.855; C15.378.243.937

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, affects cotreatment, decreases expression	3
Benzo(a)pyrene	increases methylation, increases expression	2
Valproic Acid	affects expression, decreases methylation, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	2
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
beta-lapachone	decreases expression	1
perfluorooctanoic acid	increases expression	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
nickel sulfate	increases expression	1
coumarin	increases phosphorylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
abrine	increases expression	1
PCI 5002	increases expression, affects cotreatment	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Estradiol	decreases expression	1
Ivermectin	decreases expression	1
Manganese	decreases expression, increases abundance, affects cotreatment	1
Methyl Methanesulfonate	increases expression	1
Quercetin	increases phosphorylation	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
Zinc	affects cotreatment, increases expression	1
Cyclosporine	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1TV	Abcam HeLa HPS5 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00039858	PHASE4	COMPLETED	Evaluation of Argatroban Injection in Pediatric Patients Requiring Anticoagulant Alternatives to Heparin
NCT00239733	PHASE4	TERMINATED	Anti-D for Treating Thrombocytopenia in Adults Infected With Hepatitis C Virus With or Without HIV Co-Infection
NCT00907478	PHASE4	COMPLETED	Study on Bone Marrow Morphology in Adults Receiving Romiplostim for Treatment of Thrombocytopenia Associated With Immune Thrombocytopenia Purpura (ITP)
NCT01727401	PHASE4	TERMINATED	Thromboprophylaxis of Venous Thromboembolism in Acutely-ill Medical Inpatients With Thrombocytopenia
NCT02032134	PHASE4	TERMINATED	Protocol for the Infusion of Buffy Coat-derived Cryopreserved Platelets in Patients With Severe Thrombocytopenia
NCT02267993	PHASE4	COMPLETED	Efficacy and Safety of rhTPO for the Treatment of Thrombocytopenia After Chemotherapy in AML Patients
NCT03633019	PHASE4	UNKNOWN	High-dose Use of rhTPO in CIT Patients
NCT03688191	PHASE4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04906083	PHASE4	UNKNOWN	Avatrombopag in Patients With End-stage Liver Disease and Thrombocytopenia
NCT05217719	PHASE4	UNKNOWN	Effects of Recombinant Human Thrombopoietin on Platelet Levels in ICU Patients
NCT05255003	PHASE4	RECRUITING	STrategies for Anticoagulation in Patients With thRombocytopenia and Cancer-associated Thrombosis
NCT05382013	PHASE4	UNKNOWN	Efficacy and Safety of Avatrombopag for Treating TCP in HBV-ACLF Patients Receiving ALSS Treatment
NCT05944458	PHASE4	COMPLETED	Efficacy of Intravenous N-Acetylcysteine in Preventing Linezolid-Induced Thrombocytopenia in Critically Ill Patients
NCT06562738	PHASE4	RECRUITING	Clinical Study on Efficacy and Safety of Hetrombopag in the Preoperative Patients of Thrombocytopenia
NCT00037791	PHASE3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00039910	PHASE3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00073580	PHASE3	COMPLETED	Angiomax in Patients With HIT/HITTS Type II Undergoing Off-Pump Coronary Artery Bypass Grafting (CABG) (CHOOSE)
NCT00102323	PHASE3	COMPLETED	AMG 531 Treatment of Thrombocytopenic Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) Refractory to Splenectomy
NCT00102336	PHASE3	COMPLETED	AMG 531 Treatment of Thrombocytopenic Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) Prior to Splenectomy
NCT00116688	PHASE3	COMPLETED	Open Label Extension Study of Romiplostim (AMG 531) in Thrombocytopenic Patients With Immune (Idiopathic) Thrombocytopenic Purpura (ITP)
NCT00128713	PHASE3	COMPLETED	Optimal Platelet Dose Strategy for Management of Thrombocytopenia
NCT00151866	PHASE3	COMPLETED	Efficacy of Transfusions With Platelets Stored in Platelet Additive Solution II Versus Plasma
NCT00261924	PHASE3	COMPLETED	Efficacy and Safety Study of Platelets Treated for Pathogen Inactivation and Stored for Up to Seven Days
NCT00415532	PHASE3	COMPLETED	Romiplostim (AMG 531) Versus Medical Standard of Care for Immune (Idiopathic) Thrombocytopenic Purpura
NCT00420914	PHASE3	TERMINATED	Strategies for Transfusion of Platelets (SToP)
NCT00501345	PHASE3	TERMINATED	Aspirin in Patients With Myocardial Infarction and Thrombocytopenia
NCT00508820	PHASE3	COMPLETED	An Open Label Study of Romiplostim in Adult Thrombocytopenic Subjects With ITP
NCT00678587	PHASE3	TERMINATED	Eltrombopag To Reduce The Need For Platelet Transfusion In Subjects With Chronic Liver Disease And Thrombocytopenia Undergoing Elective Invasive Procedures
NCT01438840	PHASE3	COMPLETED	Efficacy and Safety of Oral E5501 Plus Standard of Care for the Treatment of Thrombocytopenia in Adults With Chronic Immune Thrombocytopenia (Amendment 02)
NCT01444417	PHASE3	COMPLETED	Safety and Efficacy Study of Romiplostim to Treat Immune Thrombocytopenia (ITP) in Pediatric Patients
NCT01805648	PHASE3	UNKNOWN	Efficacy and Safety Study of Maintenance Treatment With rhTPO in Thrombocytopenic Subjects With ITP
NCT02244658	PHASE3	UNKNOWN	Recombinant Human Thrombopoietin (rhTPO) in Management of Chemotherapy-induced Thrombocytopenia in Acute Myelocytic Leukemia
NCT02389621	PHASE3	COMPLETED	Safety and Efficacy Study of Lusutrombopag for Thrombocytopenia in Patients With Chronic Liver Disease Undergoing Elective Invasive Procedures
NCT02444728	PHASE3	TERMINATED	Cyclophosphamide and Hydroxychloroquine for Thrombocytopenia in SLE
NCT02487563	PHASE3	COMPLETED	Prospective Study of Patients With Thrombocytopenia Following HSCT
NCT02578901	PHASE3	COMPLETED	American Trial Using Tranexamic Acid in Thrombocytopenia
NCT03326843	PHASE3	TERMINATED	Avatrombopag for the Treatment of Thrombocytopenia in Adults Scheduled for a Surgical Procedure
NCT03515096	PHASE3	COMPLETED	Eltrombopag vs. rhTPO to Increase Platelet Level After HSCT
NCT05563064	PHASE3	UNKNOWN	Effect of Herbal Formulation on Thrombocytes Count
NCT07442513	PHASE3	RECRUITING	Comparison of Etamsylate Versus Placebo to Prevent Bleeding in HSCT