Details of Disease

General Information of Disease (ID: DISCY0HQ)

• Disease Name: Hermansky-Pudlak syndrome
• Synonyms: Hermansky Pudlak syndrome; HPS (Hermansky Pudlak syndrome); HPS; Hepatopulmonary Syndrome
• Definition: Hermansky-Pudlak syndrome (HSP) is a multi-system disorder characterized by oculocutaneous albinism, bleeding diathesis and, in some cases, neutropenia, pulmonary fibrosis, or granulomatous colitis. HPS comprises eight known disorders (HPS-1 to HPS-8), the majority of which present with the same clinical phenotype to varying degrees of severity.
• Disease Hierarchy:
  DIS063EG: Syndromic oculocutaneous albinism
  DISOSIQY: Disorder of lysosomal-related organelles
  DIS1DL2M: Inherited blood coagulation disorder
  DISCY0HQ: Hermansky-Pudlak syndrome
• Disease Identifiers:
  MONDO ID: MONDO_0019312
  MESH ID: D022861
  UMLS CUI: C0079504
  MedGen ID: 36313
  Orphanet ID: 79430
  SNOMED CT ID: 9311003

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 4 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CHM	TTOA18V	Strong	Genetic Variation	[1]
RAB9A	TT958S6	Strong	Biomarker	[2]
TYR	TTULVH8	Strong	Genetic Variation	[3]
TYRP1	TTFRV98	Strong	Biomarker	[4]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC35D3	DT63MZQ	Strong	Biomarker	[5]

This Disease Is Related to 29 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
AP3D1	OTJLI0IM	Limited	Genetic Variation	[6]
PI4K2A	OTL9L6MX	Limited	Biomarker	[7]
RASGRF1	OTNWJ7EN	Limited	Biomarker	[2]
SOS1	OTTCWXC3	Limited	Biomarker	[2]
BLOC1S5	OTE3LL6Q	Moderate	Autosomal recessive	[8]
RAB38	OTU0NZU0	moderate	Biomarker	[2]
BHLHE22	OTZUQY5L	Strong	Genetic Variation	[9]
BLOC1S3	OTNRFFLW	Strong	Genetic Variation	[10]
BLOC1S4	OTDCFUJC	Strong	Genetic Variation	[11]
BLOC1S6	OT96NE03	Strong	Genetic Variation	[12]
CD63	OT2UGZA9	Strong	Biomarker	[13]
DTNBP1	OT9UQT2S	Strong	CausalMutation	[14]
FGL1	OTT0QHQ1	Strong	Genetic Variation	[15]
FUZ	OTC427QQ	Strong	Biomarker	[16]
GDI1	OTYM3928	Strong	Biomarker	[17]
HPS1	OTKS5I7T	Strong	Biomarker	[2]
HPS3	OTAKROK7	Strong	Genetic Variation	[3]
HPS4	OTBTW01J	Strong	Biomarker	[2]
HPS5	OTLO2374	Strong	Genetic Variation	[14]
HPS6	OTXL5KQW	Strong	CausalMutation	[14]
OCA2	OTDWIGBF	Strong	Biomarker	[18]
PADI1	OT13WAQX	Strong	Biomarker	[19]
PDIA2	OTC2WMXS	Strong	Biomarker	[19]
RAB32	OTTR4H7S	Strong	Biomarker	[2]
RIMS2	OTQASWDH	Strong	Genetic Variation	[20]
SFTPC	OTIZJD09	Strong	Biomarker	[21]
SLC2A4RG	OTW3LX8D	Strong	Biomarker	[2]
TCAP	OTQQMJ94	Strong	Biomarker	[22]
LYST	OTIUB1B3	Definitive	Genetic Variation	[23]

References

• [1] Prenylation of Rab GTPases: molecular mechanisms and involvement in genetic disease.FEBS Lett. 2001 Jun 8;498(2-3):197-200. doi: 10.1016/s0014-5793(01)02483-8.
• [2] The BLOC-3 subunit HPS4 is required for activation of Rab32/38 GTPases in melanogenesis, but its Rab9 activity is dispensable for melanogenesis.J Biol Chem. 2019 Apr 26;294(17):6912-6922. doi: 10.1074/jbc.RA119.007345. Epub 2019 Mar 5.
• [3] Hermansky-Pudlak syndrome and oculocutaneous albinism in Chinese children with pigmentation defects and easy bruising.Orphanet J Rare Dis. 2019 Feb 21;14(1):52. doi: 10.1186/s13023-019-1023-7.
• [4] ESCRT-I function is required for Tyrp1 transport from early endosomes to the melanosome limiting membrane.Traffic. 2009 Sep;10(9):1318-36. doi: 10.1111/j.1600-0854.2009.00955.x. Epub 2009 Jun 9.
• [5] SLC35D3 delivery from megakaryocyte early endosomes is required for platelet dense granule biogenesis and is differentially defective in Hermansky-Pudlak syndrome models.Blood. 2012 Jul 12;120(2):404-14. doi: 10.1182/blood-2011-11-389551. Epub 2012 May 18.
• [6] Biallelic mutations in AP3D1 cause Hermansky-Pudlak syndrome type 10 associated with immunodeficiency and seizure disorder.Eur J Med Genet. 2019 Nov;62(11):103583. doi: 10.1016/j.ejmg.2018.11.017. Epub 2018 Nov 22.
• [7] The WASH complex, an endosomal Arp2/3 activator, interacts with the Hermansky-Pudlak syndrome complex BLOC-1 and its cargo phosphatidylinositol-4-kinase type II.Mol Biol Cell. 2013 Jul;24(14):2269-84. doi: 10.1091/mbc.E13-02-0088. Epub 2013 May 15.
• [8] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [9] Nonsense mutations in ADTB3A cause complete deficiency of the beta3A subunit of adaptor complex-3 and severe Hermansky-Pudlak syndrome type 2.Pediatr Res. 2002 Feb;51(2):150-8. doi: 10.1203/00006450-200202000-00006.
• [10] A BLOC-1 mutation screen reveals a novel BLOC1S3 mutation in Hermansky-Pudlak Syndrome type 8.Pigment Cell Melanoma Res. 2012 Sep;25(5):584-91. doi: 10.1111/j.1755-148X.2012.01029.x. Epub 2012 Aug 2.
• [11] Defects in the cappuccino (cno) gene on mouse chromosome 5 and human 4p cause Hermansky-Pudlak syndrome by an AP-3-independent mechanism.Blood. 2000 Dec 15;96(13):4227-35.
• [12] A BLOC-1 mutation screen reveals that PLDN is mutated in Hermansky-Pudlak Syndrome type 9. Am J Hum Genet. 2011 Jun 10;88(6):778-787. doi: 10.1016/j.ajhg.2011.05.009.
• [13] Defective AP-3-dependent VAMP8 trafficking impairs Weibel-Palade body exocytosis in Hermansky-Pudlak Syndrome type 2 blood outgrowth endothelial cells.Haematologica. 2019 Oct;104(10):2091-2099. doi: 10.3324/haematol.2018.207787. Epub 2019 Jan 10.
• [14] Diagnostic high-throughput sequencing of 2396 patients with bleeding, thrombotic, and platelet disorders.Blood. 2019 Dec 5;134(23):2082-2091. doi: 10.1182/blood.2018891192.
• [15] Characterizing renal involvement in Hermansky-Pudlak Syndrome in a zebrafish model.Sci Rep. 2019 Nov 27;9(1):17718. doi: 10.1038/s41598-019-54058-5.
• [16] Hexa-Longin domain scaffolds for inter-Rab signalling.Bioinformatics. 2020 Feb 15;36(4):990-993. doi: 10.1093/bioinformatics/btz739.
• [17] Rab GTPases, intracellular traffic and disease.Trends Mol Med. 2002 Jan;8(1):23-30. doi: 10.1016/s1471-4914(01)02227-4.
• [18] A cross-sectional examination of visual acuity by specific type of albinism.J AAPOS. 2016 Oct;20(5):419-424. doi: 10.1016/j.jaapos.2016.06.006. Epub 2016 Sep 16.
• [19] Defective PDI release from platelets and endothelial cells impairs thrombus formation in Hermansky-Pudlak syndrome.Blood. 2015 Mar 5;125(10):1633-42. doi: 10.1182/blood-2014-08-597419. Epub 2015 Jan 15.
• [20] rim2 (recombination-induced mutation 2) is a new allele of pearl and a mouse model of human Hermansky-Pudlak syndrome (HPS): genetic and physical mapping.Mamm Genome. 1998 Jan;9(1):2-7. doi: 10.1007/s003359900670.
• [21] Systematic review of drug effects in humans and models with surfactant-processing disease.Eur Respir Rev. 2018 Jul 11;27(149):170135. doi: 10.1183/16000617.0135-2017. Print 2018 Sep 30.
• [22] Precise therapeutic gene correction by a simple nuclease-induced double-stranded break.Nature. 2019 Apr;568(7753):561-565. doi: 10.1038/s41586-019-1076-8. Epub 2019 Apr 3.
• [23] Molecular basis of albinism: mutations and polymorphisms of pigmentation genes associated with albinism. Hum Mutat. 1999;13(2):99-115. doi: 10.1002/(SICI)1098-1004(1999)13:2<99::AID-HUMU2>3.0.CO;2-C.