MCID: HRM017
MIFTS: 43

Hermansky-Pudlak Syndrome 2

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

Aliases & Classifications for Hermansky-Pudlak Syndrome 2

MalaCards integrated aliases for Hermansky-Pudlak Syndrome 2:

Name: Hermansky-Pudlak Syndrome 2 57 12 53 75 13 15 73
Hps2 57 53 59 75
Hermansky Pudlak Syndrome 2 53 29 6
Albinism with Hemorrhagic Diathesis and Pigmented Reticuloendothelial Cells 73
Albinism with Hemorrhagic Diathesis and Pigmented Reticuloendothelial 75
Platelet Defects and Oculocutaneous Albinism 53
Hermansky-Pudlak Syndrome with Neutropenia 59
Hermansky-Pudlak Syndrome, Type 2 40
Platelet Storage Pool Deficiency 73
Hermansky-Pudlak Syndrome Type 2 59
Delta Storage Pool Disease 75

Characteristics:

Orphanet epidemiological data:

59
hermansky-pudlak syndrome with neutropenia
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide);

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
onset at birth
genetic heterogeneity, see


HPO:

32
hermansky-pudlak syndrome 2:
Onset and clinical course congenital onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Hermansky-Pudlak Syndrome 2

NIH Rare Diseases : 53 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.

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 and abdominal pain. An important gene associated with Hermansky-Pudlak Syndrome 2 is AP3B1 (Adaptor Related Protein Complex 3 Subunit Beta 1), 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 neutrophil, and related phenotypes are thin upper lip vermilion and microcephaly

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 : 57 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 : 75 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:

57
Head And Neck Ears:
low-set ears
posteriorly rotated ears

Head And Neck Face:
coarse facial features
long, flat philtrum
protruding midface

AbdomenSpleen:
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 Eyes:
nystagmus
photophobia
strabismus
upslanting palpebral fissures
decreased visual acuity
more
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:

32 (show all 30)
# Description HPO Frequency HPO Source Accession
1 thin upper lip vermilion 32 HP:0000219
2 microcephaly 32 HP:0000252
3 coarse facial features 32 HP:0000280
4 smooth philtrum 32 HP:0000319
5 long philtrum 32 HP:0000343
6 posteriorly rotated ears 32 HP:0000358
7 low-set ears 32 HP:0000369
8 wide nasal bridge 32 HP:0000431
9 strabismus 32 HP:0000486
10 visual impairment 32 HP:0000505
11 upslanted palpebral fissure 32 HP:0000582
12 photophobia 32 HP:0000613
13 nystagmus 32 HP:0000639
14 carious teeth 32 HP:0000670
15 periodontitis 32 HP:0000704
16 albinism 32 HP:0001022
17 ocular albinism 32 HP:0001107
18 intellectual disability, mild 32 HP:0001256
19 motor delay 32 HP:0001270
20 hip dysplasia 32 HP:0001385
21 splenomegaly 32 HP:0001744
22 thrombocytopenia 32 HP:0001873
23 neutropenia 32 HP:0001875
24 pulmonary fibrosis 32 HP:0002206
25 hepatomegaly 32 HP:0002240
26 fair hair 32 HP:0002286
27 recurrent bacterial infections 32 HP:0002718
28 aberrant melanosome maturation 32 HP:0007384
29 reduced visual acuity 32 HP:0007663
30 acetabular dysplasia 32 HP:0008807

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:

26
# 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 54-11-5 942 89594
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 29 AP3B1

Anatomical Context for Hermansky-Pudlak Syndrome 2

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

41
Lung, Skin, Neutrophil, Eye

Publications for Hermansky-Pudlak Syndrome 2

Articles related to Hermansky-Pudlak Syndrome 2:

(show all 12)
# Title Authors Year
1
Hermansky-Pudlak syndrome type 2 manifests with fibrosing lung disease early in childhood. ( 29580292 )
2018
2
Hermansky-Pudlak syndrome type 2: Aberrant pre-mRNA splicing and mislocalization of granule proteins in neutrophils. ( 28585318 )
2017
3
Generation of Hermansky Pudlak syndrome type 2 (HPS2) induced pluripotent stem cells (iPSCs). ( 27345985 )
2016
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
Disruption of AP3B1 by a chromosome 5 inversion: a new disease mechanism in Hermansky-Pudlak syndrome type 2. ( 23557002 )
2013
7
Interstitial lung disease and pulmonary fibrosis in Hermansky-Pudlak syndrome type 2, an adaptor protein-3 complex disease. ( 22009278 )
2012
8
Defective HIV-1 particle assembly in AP-3-deficient cells derived from patients with Hermansky-Pudlak syndrome type 2. ( 22875976 )
2012
9
Two patients with Hermansky Pudlak syndrome type 2 and novel mutations in AP3B1. ( 19679886 )
2010
10
Novel mutation causing Hermansky-Pudlak Syndrome Type 2. ( 20981699 )
2010
11
Identification of a homozygous deletion in the AP3B1 gene causing Hermansky-Pudlak syndrome, type 2. ( 16537806 )
2006
12
Nonsense mutations in ADTB3A cause complete deficiency of the beta3A subunit of adaptor complex-3 and severe Hermansky-Pudlak syndrome type 2. ( 11809908 )
2002

Variations for Hermansky-Pudlak Syndrome 2

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

75
# 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 top 50) (show all 82)
# Gene Variation Type Significance SNP ID Assembly Location
1 AP3B1 NM_003664.4(AP3B1): c.1168_1230del63 (p.Leu390_Gln410del) deletion Pathogenic GRCh38 Chromosome 5, 78165610: 78165672
2 AP3B1 NM_003664.4(AP3B1): c.1168_1230del63 (p.Leu390_Gln410del) deletion Pathogenic GRCh37 Chromosome 5, 77461434: 77461496
3 AP3B1 NM_003664.4(AP3B1): c.1739T> G (p.Leu580Arg) single nucleotide variant Pathogenic rs121908904 GRCh37 Chromosome 5, 77425043: 77425043
4 AP3B1 NM_003664.4(AP3B1): c.1739T> G (p.Leu580Arg) single nucleotide variant Pathogenic rs121908904 GRCh38 Chromosome 5, 78129219: 78129219
5 AP3B1 AP3B1, 1-BP INS, 1618G insertion Pathogenic
6 AP3B1 AP3B1, IVS14DS, T-C, +6 single nucleotide variant Pathogenic
7 AP3B1 NM_003664.4(AP3B1): c.1474-7072_1650+921del deletion Pathogenic GRCh37 Chromosome 5, 77436046: 77444215
8 AP3B1 NM_003664.4(AP3B1): c.1474-7072_1650+921del deletion Pathogenic GRCh38 Chromosome 5, 78140222: 78148391
9 AP3B1 NM_003664.4(AP3B1): c.904A> T (p.Arg302Ter) single nucleotide variant Pathogenic rs121908905 GRCh37 Chromosome 5, 77477369: 77477369
10 AP3B1 NM_003664.4(AP3B1): c.904A> T (p.Arg302Ter) single nucleotide variant Pathogenic rs121908905 GRCh38 Chromosome 5, 78181545: 78181545
11 AP3B1 NM_003664.4(AP3B1): c.1525C> T (p.Arg509Ter) single nucleotide variant Pathogenic rs121908906 GRCh37 Chromosome 5, 77437092: 77437092
12 AP3B1 NM_003664.4(AP3B1): c.1525C> T (p.Arg509Ter) single nucleotide variant Pathogenic rs121908906 GRCh38 Chromosome 5, 78141268: 78141268
13 AP3B1 NM_003664.4(AP3B1): c.1975G> T (p.Glu659Ter) single nucleotide variant Pathogenic rs121908907 GRCh37 Chromosome 5, 77412052: 77412052
14 AP3B1 NM_003664.4(AP3B1): c.1975G> T (p.Glu659Ter) single nucleotide variant Pathogenic rs121908907 GRCh38 Chromosome 5, 78116228: 78116228
15 AP3B1 NM_003664.4(AP3B1): c.1317T> G (p.Thr439=) single nucleotide variant Conflicting interpretations of pathogenicity rs75248449 GRCh37 Chromosome 5, 77458689: 77458689
16 AP3B1 NM_003664.4(AP3B1): c.1317T> G (p.Thr439=) single nucleotide variant Conflicting interpretations of pathogenicity rs75248449 GRCh38 Chromosome 5, 78162865: 78162865
17 AP3B1 NM_003664.4(AP3B1): c.2409_2411delGAA (p.Lys804del) deletion Benign/Likely benign rs199702315 GRCh37 Chromosome 5, 77396836: 77396838
18 AP3B1 NM_003664.4(AP3B1): c.2409_2411delGAA (p.Lys804del) deletion Benign/Likely benign rs199702315 GRCh38 Chromosome 5, 78101012: 78101014
19 AP3B1 NM_003664.4(AP3B1): c.2995G> A (p.Val999Met) single nucleotide variant Conflicting interpretations of pathogenicity rs146503597 GRCh37 Chromosome 5, 77311370: 77311370
20 AP3B1 NM_003664.4(AP3B1): c.2995G> A (p.Val999Met) single nucleotide variant Conflicting interpretations of pathogenicity rs146503597 GRCh38 Chromosome 5, 78015546: 78015546
21 AP3B1 NM_003664.4(AP3B1): c.2661C> A (p.Phe887Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs139344924 GRCh37 Chromosome 5, 77335015: 77335015
22 AP3B1 NM_003664.4(AP3B1): c.2661C> A (p.Phe887Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs139344924 GRCh38 Chromosome 5, 78039191: 78039191
23 AP3B1 NM_003664.4(AP3B1): c.2613C> T (p.His871=) single nucleotide variant Conflicting interpretations of pathogenicity rs144420604 GRCh38 Chromosome 5, 78039239: 78039239
24 AP3B1 NM_003664.4(AP3B1): c.2613C> T (p.His871=) single nucleotide variant Conflicting interpretations of pathogenicity rs144420604 GRCh37 Chromosome 5, 77335063: 77335063
25 AP3B1 NM_003664.4(AP3B1): c.2702C> G (p.Ser901Cys) single nucleotide variant Pathogenic rs869312835 GRCh37 Chromosome 5, 77334974: 77334974
26 AP3B1 NM_003664.4(AP3B1): c.2702C> G (p.Ser901Cys) single nucleotide variant Pathogenic rs869312835 GRCh38 Chromosome 5, 78039150: 78039150
27 AP3B1 NM_003664.4(AP3B1): c.1839_1842delTAGA (p.Asp613Glufs) deletion Pathogenic rs869312839 GRCh37 Chromosome 5, 77423980: 77423983
28 AP3B1 NM_003664.4(AP3B1): c.1839_1842delTAGA (p.Asp613Glufs) deletion Pathogenic rs869312839 GRCh38 Chromosome 5, 78128156: 78128159
29 AP3B1 NM_003664.4(AP3B1): c.1754delT (p.Val585Glufs) deletion Pathogenic rs869312836 GRCh37 Chromosome 5, 77425028: 77425028
30 AP3B1 NM_003664.4(AP3B1): c.1754delT (p.Val585Glufs) deletion Pathogenic rs869312836 GRCh38 Chromosome 5, 78129204: 78129204
31 AP3B1 NM_003664.4(AP3B1): c.716G> A (p.Trp239Ter) single nucleotide variant Pathogenic rs869312837 GRCh37 Chromosome 5, 77511949: 77511949
32 AP3B1 NM_003664.4(AP3B1): c.716G> A (p.Trp239Ter) single nucleotide variant Pathogenic rs869312837 GRCh38 Chromosome 5, 78216125: 78216125
33 AP3B1 NM_003664.4(AP3B1): c.177delA (p.Lys59Asnfs) deletion Pathogenic rs869312838 GRCh37 Chromosome 5, 77563371: 77563371
34 AP3B1 NM_003664.4(AP3B1): c.177delA (p.Lys59Asnfs) deletion Pathogenic rs869312838 GRCh38 Chromosome 5, 78267547: 78267547
35 AP3B1 NM_003664.4(AP3B1): c.3023_3025delCTG (p.Ala1008del) deletion Benign/Likely benign rs111935323 GRCh38 Chromosome 5, 78015516: 78015518
36 AP3B1 NM_003664.4(AP3B1): c.3023_3025delCTG (p.Ala1008del) deletion Benign/Likely benign rs111935323 GRCh37 Chromosome 5, 77311340: 77311342
37 AP3B1 NM_003664.4(AP3B1): c.687A> G (p.Leu229=) single nucleotide variant Benign/Likely benign rs35496909 GRCh38 Chromosome 5, 78216154: 78216154
38 AP3B1 NM_003664.4(AP3B1): c.687A> G (p.Leu229=) single nucleotide variant Benign/Likely benign rs35496909 GRCh37 Chromosome 5, 77511978: 77511978
39 AP3B1 NM_003664.4(AP3B1): c.339A> C (p.Ala113=) single nucleotide variant Benign/Likely benign rs7706167 GRCh37 Chromosome 5, 77524004: 77524004
40 AP3B1 NM_003664.4(AP3B1): c.339A> C (p.Ala113=) single nucleotide variant Benign/Likely benign rs7706167 GRCh38 Chromosome 5, 78228180: 78228180
41 AP3B1 NM_003664.4(AP3B1): c.2730T> C (p.Thr910=) single nucleotide variant Benign rs143527588 GRCh37 Chromosome 5, 77334946: 77334946
42 AP3B1 NM_003664.4(AP3B1): c.2730T> C (p.Thr910=) single nucleotide variant Benign rs143527588 GRCh38 Chromosome 5, 78039122: 78039122
43 AP3B1 NM_003664.4(AP3B1): c.3131+5G> T single nucleotide variant Uncertain significance rs191616060 GRCh37 Chromosome 5, 77311229: 77311229
44 AP3B1 NM_003664.4(AP3B1): c.3131+5G> T single nucleotide variant Uncertain significance rs191616060 GRCh38 Chromosome 5, 78015405: 78015405
45 AP3B1 NM_003664.4(AP3B1): c.2324T> A (p.Ile775Lys) single nucleotide variant Benign/Likely benign rs62001050 GRCh38 Chromosome 5, 78110280: 78110280
46 AP3B1 NM_003664.4(AP3B1): c.2324T> A (p.Ile775Lys) single nucleotide variant Benign/Likely benign rs62001050 GRCh37 Chromosome 5, 77406104: 77406104
47 AP3B1 NM_003664.4(AP3B1): c.3207G> A (p.Gln1069=) single nucleotide variant Conflicting interpretations of pathogenicity rs34089426 GRCh37 Chromosome 5, 77298804: 77298804
48 AP3B1 NM_003664.4(AP3B1): c.3207G> A (p.Gln1069=) single nucleotide variant Conflicting interpretations of pathogenicity rs34089426 GRCh38 Chromosome 5, 78002980: 78002980
49 AP3B1 NM_003664.4(AP3B1): c.2880C> T (p.Ala960=) single nucleotide variant Conflicting interpretations of pathogenicity rs62001052 GRCh38 Chromosome 5, 78034375: 78034375
50 AP3B1 NM_003664.4(AP3B1): c.2880C> T (p.Ala960=) single nucleotide variant Conflicting interpretations of pathogenicity rs62001052 GRCh37 Chromosome 5, 77330199: 77330199

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 lysosomal membrane GO:0005765 8.62 AP3B1 LAMP1

Sources for Hermansky-Pudlak Syndrome 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
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30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
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45 MESH via Orphanet
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62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
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74 UMLS via Orphanet
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