This report includes information relevant to a potential model of Hermansky-Pudlak syndrome 5 (HPS5), which is a subtype of Hermansky-Pudlak syndrome. The human gene implicated in this disease is HPS5, which encodes a protein that may play a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. There is one high-scoring fly ortholog, p (pink), for which RNAi targeting constructs, alleles caused by insertional mutagenesis, and classical amorphic alleles have been generated.
Human HPS5 has not yet been introduced into flies.
For multiple subtypes of Hermansky-Pudlak syndrome, the implicated gene encodes a subunit of a BLOC complex, in this case the BLOC2 complex.
[updated Aug. 2018 by FlyBase; FBrf0222196]
Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder in which oculocutaneous albinism, bleeding, and lysosomal ceroid storage result from defects of multiple cytoplasmic organelles: melanosomes, platelet-dense granules, and lysosomes (Oh et al., 1998, pubmed:9497254). [from MIM:115200, 2016.03.25]
Hermansky-Pudlak syndrome (HPS) is a multisystem disorder characterized by: tyrosinase-positive oculocutaneous albinism; a bleeding diathesis resulting from a platelet storage pool deficiency; and, in some cases, pulmonary fibrosis, granulomatous colitis, or immunodeficiency. The albinism is characterized by: hypopigmentation of the skin and hair; and ocular findings of reduced iris pigment with iris transillumination, reduced retinal pigment, foveal hypoplasia with significant reduction in visual acuity (usually in the range of 20/50 to 20/400), nystagmus, and increased crossing of the optic nerve fibers. Hair color ranges from white to brown; skin color ranges from white to olive and is usually a shade lighter than that of other family members. The bleeding diathesis can result in easy bruising, frequent epistaxis, gingival bleeding, postpartum hemorrhage, colonic bleeding, and prolonged bleeding with menses or after tooth extraction, circumcision, and other surgeries. Pulmonary fibrosis, a restrictive lung disease, typically causes symptoms in the early thirties and can progress to death within a decade. Granulomatous colitis is severe in about 15% of affected individuals. Neutropenia and/or immune defects are associated primarily with HPS-2. [from GeneReviews, Hermansky-Pudlak Syndrome, pubmed:20301486 2016.01.26]
[HERMANSKY-PUDLAK SYNDROME 5; HPS5](https://omim.org/entry/614074)
[HPS5 BIOGENESIS OF LYSOSOMAL ORGANELLES COMPLEX 2, SUBUNIT 2; HPS5](https://omim.org/entry/607521)
A Hermansky-Pudlak syndrome patient with a mutation in the HP5 gene was described as having clinically mild oculocutaneous albinism and easy bruising. The patient had a moderately reducted platelet count and a moderately prolonged bleeding time (Zhang, et al., 2003, pubmed:12548288). [From MIM:614074, 2016.03.25]
Hermansky-Pudlak syndrome-5 (HPS5) is caused by homozygous mutation in the HPS5 gene [From MIM:614074, 2016.03.25]
Hermansky-Pudlak syndrome-5 has been modeled in mice through mutation of the murine HPS5 ortholog ru2 (ruby-eye-2). Affected mice have normal lysosomal morphology, while kidney proximal tubule cells secrete lysosomal enzymes into urine at greatly reduced rates. Platelet dense granules are very deficient in critical components such as serotonin and adenine nucleotides, leading to functionally abnormal platelets and prolonged bleeding times (Zhang, et al., 2003, pubmed:12548288). [From MIM:607521, 2016.03.25]
HPS5 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. [provided by RefSeq, Jul 2008]
The mutation associated with Hermansky-Pudlak syndrome 5 is a 4-bp deletion (AGTT) at codons leu675 to val676 in the HPS5 gene. The mutation results in a frameshift with truncation of the nonsense polypeptide at codon 682, causing loss of 40% of the protein at the C terminus (Zhang, et al., 2003, pubmed:12548288). [From MIM:614074 and MIM:607521, 2016.03.25]
One to one: 1 human to 1 Drosophila.
