HPS4 gene


Gene (OMIM No.)
Function of gene/protein
  • Protein: subunit 2 of the biogenesis of lysosome-related organelles complex-3 (BLOC-3)
  • BLOC-3 complex plays an important role in the control of melanin production and melanosome biogenesis by promoting membrane recruitment of specific Rab GTPases (Rab32 and Rab38)
Clinical phenotype
(OMIM phenotype no.)
  • Hermansky-Pudlak syndrome 4 (#614073)
  • Autosomal recessive
Ocular features
  • Albinism
  • Intra- and interfamilial variability in disease severity
Systemic features
  • Skin and hair depigmentation
  • Bleeding diathesis due to platelet storage pool deficiency (easy/prolonged bleeding, easy bruising, prolonged/heavy menorrhagia, epistaxis)
  • At risk of developing pulmonary fibrosis (onset usually during early 30s) and granulomatous colitis
Key investigations
  • Orthoptic assessment and refraction
  • OCT to detect foveal hypoplasia
  • Visual evoked potentials to detect evidence of chiasmal misrouting
  • Eye movement recordings
  • Systemic assessment with a pediatrician, haematologists and other relevant specialists
Molecular diagnosisNext generation sequencing
  • Targeted gene panels (albinism)
  • Whole exome sequencing
  • Whole genome sequencing
  • Multidisciplinary approach
Therapies under research
Further information

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Additional information

Hermansky-Pudlak syndrome (HPS) patients with BLOC-3 defects (HPS1 or HPS4) have more severe ocular and systemic phenotypes compared to those with BLOC-2 defects (HPS3, HPS5 and HPS6).[2] 

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  1.  Gerondopoulos A, Langemeyer L, Liang JR, Linford A, Barr FA. BLOC-3 mutated in Hermansky-Pudlak syndrome is a Rab32/38 guanine nucleotide exchange factor. Curr Biol. 2012;22(22):2135-2139
  2.  Huizing M, Helip-Wooley A, Westbroek W, Gunay-Aygun M, Gahl WA. Disorders of lysosome-related organelle biogenesis: clinical and molecular genetics. Annu Rev Genomics Hum Genet. 2008;9:359-386
  3.  Suzuki T, Li W, Zhang Q, et al. Hermansky-Pudlak syndrome is caused by mutations in HPS4, the human homolog of the mouse light-ear gene. Nat Genet. 2002;30(3):321-324
  4.  Anderson PD, Huizing M, Claassen DA, White J, Gahl WA. Hermansky-Pudlak syndrome type 4 (HPS-4): clinical and molecular characteristics. Hum Genet. 2003;113(1):10-17
  5.  Bachli EB, Brack T, Eppler E, et al. Hermansky-Pudlak syndrome type 4 in a patient from Sri Lanka with pulmonary fibrosis. Am J Med Genet A. 2004;127A(2):201-207

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Updated on November 30, 2020
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