MCID: HRM017
MIFTS: 45

Hermansky-Pudlak Syndrome 2

Categories: Genetic diseases, Rare diseases, Blood diseases, Eye diseases, Skin diseases, Metabolic diseases

Aliases & Classifications for Hermansky-Pudlak Syndrome 2

MalaCards integrated aliases for Hermansky-Pudlak Syndrome 2:

Name: Hermansky-Pudlak Syndrome 2 53 12 49 71 13 14 69
Hps2 53 49 55 71
Hermansky Pudlak Syndrome 2 49 28
Albinism with Hemorrhagic Diathesis and Pigmented Reticuloendothelial Cells 69
Albinism with Hemorrhagic Diathesis and Pigmented Reticuloendothelial 71
Platelet Defects and Oculocutaneous Albinism 49
Hermansky-Pudlak Syndrome with Neutropenia 55
Platelet Storage Pool Deficiency 69
Hermansky-Pudlak Syndrome Type 2 55
Delta Storage Pool Disease 71

Characteristics:

Orphanet epidemiological data:

55
hermansky-pudlak syndrome with neutropenia
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide);

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
onset at birth
genetic heterogeneity, see


HPO:

31
hermansky-pudlak syndrome 2:
Onset and clinical course congenital onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Hermansky-Pudlak Syndrome 2

NIH Rare Diseases : 49 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 183678Disease definitionHermansky-Pudlak syndrome type 2 (HPS-2) is a type of Hermansky-Pudlak syndrome (HPS; see this term), a multi-system disorder characterized by oculocutaneous albinism, bleeding diathesis and neutropenia.EpidemiologyTo date HPS-2 has been described in eight patients.Clinical descriptionHPS-2 presents with features of HPS including oculocutaneous albinisim, reduced visual acuity, horizontal nystagmus, easy bruising of soft tissues, epistaxis, and prolonged bleeding after dental extraction, surgery or childbirth. Women may present with medically significant menstrual bleeding. In addition, HPS-2 patients present with recurrent infections due to neutropenia and impaired cytotoxic activity. Recently, pulmonary fibrosis has been described in some HPS-2 cases.EtiologyHPS-2 is caused by mutations in the AP3B1 gene (5q14.1) and is transmitted in an autosomal recessive manner. The gene product is the Beta 3A subunit of adaptor protein 3 (AP3), involved in vesicle formation and protein sorting.Management and treatmentThe neutropenia is responsive to granulocyte-cell stimulating factor (G-CSF).Visit the Orphanet disease page for more resources. Last updated: 3/30/2010

MalaCards based summary : Hermansky-Pudlak Syndrome 2, also known as hps2, is related to isolated delta-storage pool disease and hermansky-pudlak syndrome 1, and has symptoms including photophobia, low-set ears and nystagmus. An important gene associated with Hermansky-Pudlak Syndrome 2 is AP3B1 (Adaptor Related Protein Complex 3 Beta 1 Subunit), and among its related pathways/superpathways is Lysosome. The drugs Ezetimibe and Nicotine have been mentioned in the context of this disorder. Affiliated tissues include lung, skin and eye, and related phenotypes are Decreased viability after Maraba virus infection and Decreased viability after Maraba virus infection

Disease Ontology : 12 A Hermansky-Pudlak syndrome that has material basis in homozygous or compound heterozygous mutation in the gene encoding the beta-3A subunit of the AP3 complex (AP3B1) on chromosome 5q14.1.

OMIM : 53 Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disease characterized by platelet defects and oculocutaneous albinism. HPS2 differs from the other forms of HPS in that it includes immunodeficiency, and patients with HPS2 have an increased susceptibility to infections due to congenital neutropenia (Jung et al., 2006). (608233)

UniProtKB/Swiss-Prot : 71 Hermansky-Pudlak syndrome 2: 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. HPS2 differs from the other forms of HPS in that it includes immunodeficiency in its phenotype and patients with HPS2 have an increased susceptibility to infections.

Related Diseases for Hermansky-Pudlak Syndrome 2

Graphical network of the top 20 diseases related to Hermansky-Pudlak Syndrome 2:



Diseases related to Hermansky-Pudlak Syndrome 2

Symptoms & Phenotypes for Hermansky-Pudlak Syndrome 2

Symptoms via clinical synopsis from OMIM:

53
Head And Neck Eyes:
photophobia
nystagmus
strabismus
upslanting palpebral fissures
decreased visual acuity
more
Head And Neck Face:
coarse facial features
long, flat philtrum
protruding midface

Abdomen Spleen:
splenomegaly

Head And Neck Head:
microcephaly

Immunology:
neutropenia
recurrent bacterial infections
neutrophils show disorganized lysosomal compartments on ultrastructural analysis
decreased numbers of natural killer cells (nk)

Head And Neck Mouth:
thin upper lip

Neurologic Central Nervous System:
mental retardation, mild
motor retardation, mild

Head And Neck Teeth:
dental decay due to recurrent bacterial periodontitis

Head And Neck Ears:
low-set ears
posteriorly rotated ears

Skeletal Pelvis:
hip dysplasia
dysplastic acetabulae

Abdomen Liver:
hepatomegaly

Hematology:
thrombocytopenia
absence of platelet dense bodies

Skin Nails Hair Hair:
fair hair
aberrant melanosome maturation

Skin Nails Hair Skin:
fair skin
cutaneous albinism, tyrosinase-positive
aberrant melanosome maturation

Head And Neck Nose:
broad nasal root

Respiratory Lung:
pulmonary fibrosis due to recurrent infections


Clinical features from OMIM:

608233

Human phenotypes related to Hermansky-Pudlak Syndrome 2:

31 (show all 30)
# Description HPO Frequency HPO Source Accession
1 photophobia 31 HP:0000613
2 low-set ears 31 HP:0000369
3 nystagmus 31 HP:0000639
4 coarse facial features 31 HP:0000280
5 hip dysplasia 31 HP:0001385
6 splenomegaly 31 HP:0001744
7 hepatomegaly 31 HP:0002240
8 wide nasal bridge 31 HP:0000431
9 carious teeth 31 HP:0000670
10 microcephaly 31 HP:0000252
11 smooth philtrum 31 HP:0000319
12 visual impairment 31 HP:0000505
13 intellectual disability, mild 31 HP:0001256
14 pulmonary fibrosis 31 HP:0002206
15 long philtrum 31 HP:0000343
16 strabismus 31 HP:0000486
17 reduced visual acuity 31 HP:0007663
18 thrombocytopenia 31 HP:0001873
19 upslanted palpebral fissure 31 HP:0000582
20 thin upper lip vermilion 31 HP:0000219
21 periodontitis 31 HP:0000704
22 neutropenia 31 HP:0001875
23 motor delay 31 HP:0001270
24 ocular albinism 31 HP:0001107
25 recurrent bacterial infections 31 HP:0002718
26 posteriorly rotated ears 31 HP:0000358
27 albinism 31 HP:0001022
28 acetabular dysplasia 31 HP:0008807
29 fair hair 31 HP:0002286
30 aberrant melanosome maturation 31 HP:0007384

UMLS symptoms related to Hermansky-Pudlak Syndrome 2:


photophobia, abdominal pain

GenomeRNAi Phenotypes related to Hermansky-Pudlak Syndrome 2 according to GeneCards Suite gene sharing:

25
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability after Maraba virus infection GR00252-A-1 9.35 WDTC1
2 Decreased viability after Maraba virus infection GR00252-A-2 9.35 LAMP1 WDTC1
3 Decreased viability after Maraba virus infection GR00252-A-3 9.35 LAMP1 WDTC1
4 FOXO1 nuclear localization GR00247-A-1 8.8 LAMP1 WDTC1
5 FOXO1 nuclear localization GR00247-A-2 8.8 WDTC1

Drugs & Therapeutics for Hermansky-Pudlak Syndrome 2

Drugs for Hermansky-Pudlak Syndrome 2 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 21)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Ezetimibe Approved Phase 3 163222-33-1 150311
2
Nicotine Approved Phase 3 54-11-5 89594 942
3
Simvastatin Approved Phase 3 79902-63-9 54454
4
Folic Acid Approved, Nutraceutical, Vet_approved Phase 3 59-30-3 6037
5
Niacin Approved, Investigational, Nutraceutical Phase 3 59-67-6 938
6
Nicotinamide Approved, Investigational, Nutraceutical Phase 3 98-92-0 936
7 Anticholesteremic Agents Phase 3
8 Antimetabolites Phase 3
9 Ezetimibe, Simvastatin Drug Combination Phase 3
10 Hydroxymethylglutaryl-CoA Reductase Inhibitors Phase 3
11 Hypolipidemic Agents Phase 3
12 Lipid Regulating Agents Phase 3
13 Micronutrients Phase 3
14 Nicotinic Acids Phase 3
15 Trace Elements Phase 3
16 Vasodilator Agents Phase 3
17 Vitamin B Complex Phase 3
18 Vitamins Phase 3
19 Folate Nutraceutical Phase 3
20 Vitamin B3 Nutraceutical Phase 3
21 Vitamin B9 Nutraceutical Phase 3

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Treatment of HDL to Reduce the Incidence of Vascular Events HPS2-THRIVE Completed NCT00461630 Phase 3 ER niacin/laropiprant;simvastatin;ezetimibe/simvastatin
2 A Longitudinal Study of Hermansky-Pudlak Syndrome Pulmonary Fibrosis Recruiting NCT02368340

Search NIH Clinical Center for Hermansky-Pudlak Syndrome 2

Genetic Tests for Hermansky-Pudlak Syndrome 2

Genetic tests related to Hermansky-Pudlak Syndrome 2:

# Genetic test Affiliating Genes
1 Hermansky Pudlak Syndrome 2 28 AP3B1

Anatomical Context for Hermansky-Pudlak Syndrome 2

MalaCards organs/tissues related to Hermansky-Pudlak Syndrome 2:

38
Lung, Skin, Eye, Neutrophil

Publications for Hermansky-Pudlak Syndrome 2

Articles related to Hermansky-Pudlak Syndrome 2:

(show all 13)
# Title Authors Year
1
Hermansky-Pudlak syndrome type 2: Aberrant pre-mRNA splicing and mislocalization of granule proteins in neutrophils. ( 28585318 )
2017
2
Generation of Hermansky Pudlak syndrome type 2 (HPS2) induced pluripotent stem cells (iPSCs). ( 27345985 )
2016
3
Disruption of AP3B1 by a chromosome 5 inversion: a new disease mechanism in Hermansky-Pudlak syndrome type 2. ( 23557002 )
2013
4
The risk of hemophagocytic lymphohistiocytosis in Hermansky-Pudlak syndrome type 2. ( 23403622 )
2013
5
Novel mutation in Hermansky-Pudlak syndrome type 2 with mild immunological phenotype. ( 23215637 )
2013
6
Defective HIV-1 particle assembly in AP-3-deficient cells derived from patients with Hermansky-Pudlak syndrome type 2. ( 22875976 )
2012
7
Interstitial lung disease and pulmonary fibrosis in Hermansky-Pudlak syndrome type 2, an adaptor protein-3 complex disease. ( 22009278 )
2012
8
Two patients with Hermansky Pudlak syndrome type 2 and novel mutations in AP3B1. ( 19679886 )
2010
9
Novel mutation causing Hermansky-Pudlak Syndrome Type 2. ( 20981699 )
2010
10
Identification of a homozygous deletion in the AP3B1 gene causing Hermansky-Pudlak syndrome, type 2. ( 16537806 )
2006
11
Nonsense mutations in ADTB3A cause complete deficiency of the beta3A subunit of adaptor complex-3 and severe Hermansky-Pudlak syndrome type 2. ( 11809908 )
2002
12
The Hermansky-Pudlak syndrome 1 (HPS1) and HPS2 genes independently contribute to the production and function of platelet dense granules, melanosomes, and lysosomes. ( 11861280 )
2002
13
Comparison of the amino acid sequences of human protamines HP2 and HP3 and of intermediate basic nuclear proteins HPS1 and HPS2. Structural evidence that HPS1 and HPS2 are pro-protamines. ( 3403514 )
1988

Variations for Hermansky-Pudlak Syndrome 2

UniProtKB/Swiss-Prot genetic disease variations for Hermansky-Pudlak Syndrome 2:

71
# Symbol AA change Variation ID SNP ID
1 AP3B1 p.Leu580Arg VAR_011596 rs121908904

ClinVar genetic disease variations for Hermansky-Pudlak Syndrome 2:

6 (show all 13)
# Gene Variation Type Significance SNP ID Assembly Location
1 AP3B1 NM_003664.4(AP3B1): c.1975G> T (p.Glu659Ter) single nucleotide variant Pathogenic rs121908907 GRCh37 Chromosome 5, 77412052: 77412052
2 AP3B1 NM_003664.4(AP3B1): c.1168_1230del63 (p.Leu390_Gln410del) deletion Pathogenic GRCh38 Chromosome 5, 78165610: 78165672
3 AP3B1 NM_003664.4(AP3B1): c.1739T> G (p.Leu580Arg) single nucleotide variant Pathogenic rs121908904 GRCh37 Chromosome 5, 77425043: 77425043
4 AP3B1 AP3B1, 1-BP INS, 1618G insertion Pathogenic
5 AP3B1 AP3B1, IVS14DS, T-C, +6 single nucleotide variant Pathogenic
6 AP3B1 NM_003664.4(AP3B1): c.1474-7072_1650+921del deletion Pathogenic GRCh37 Chromosome 5, 77436046: 77444215
7 AP3B1 NM_003664.4(AP3B1): c.904A> T (p.Arg302Ter) single nucleotide variant Pathogenic rs121908905 GRCh37 Chromosome 5, 77477369: 77477369
8 AP3B1 NM_003664.4(AP3B1): c.1525C> T (p.Arg509Ter) single nucleotide variant Pathogenic rs121908906 GRCh37 Chromosome 5, 77437092: 77437092
9 AP3B1 NM_003664.4(AP3B1): c.2702C> G (p.Ser901Cys) single nucleotide variant Pathogenic rs869312835 GRCh37 Chromosome 5, 77334974: 77334974
10 AP3B1 NM_003664.4(AP3B1): c.1839_1842delTAGA (p.Asp613Glufs) deletion Pathogenic rs869312839 GRCh37 Chromosome 5, 77423980: 77423983
11 AP3B1 NM_003664.4(AP3B1): c.1754delT (p.Val585Glufs) deletion Pathogenic rs869312836 GRCh37 Chromosome 5, 77425028: 77425028
12 AP3B1 NM_003664.4(AP3B1): c.716G> A (p.Trp239Ter) single nucleotide variant Pathogenic rs869312837 GRCh37 Chromosome 5, 77511949: 77511949
13 AP3B1 NM_003664.4(AP3B1): c.177delA (p.Lys59Asnfs) deletion Pathogenic rs869312838 GRCh37 Chromosome 5, 77563371: 77563371

Expression for Hermansky-Pudlak Syndrome 2

Search GEO for disease gene expression data for Hermansky-Pudlak Syndrome 2.

Pathways for Hermansky-Pudlak Syndrome 2

Pathways related to Hermansky-Pudlak Syndrome 2 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.71 AP3B1 LAMP1

GO Terms for Hermansky-Pudlak Syndrome 2

Cellular components related to Hermansky-Pudlak Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytoplasmic vesicle GO:0031410 8.96 AP3B1 LAMP1
2 lysosomal membrane GO:0005765 8.62 AP3B1 LAMP1

Sources for Hermansky-Pudlak Syndrome 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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