HPS4 Gene

Name	Hermansky-Pudlak syndrome 4
Description	This gene encodes a protein component of biogenesis of lysosome-related organelles complexes (BLOC). BLOC complexes are important for the formation of endosomal-lysosomal organelles such as melanosomes and platelet dense granules. Mutations in this gene result in subtype 4 of Hermansky-Pudlak syndrome, a form of albinism. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n HPS4 encodes a subunit protein that functions as an integral component of the biogenesis of lysosome‐related organelles complex 3 (BLOC‐3). In conjunction with HPS1, HPS4 forms a stable heterodimer that plays a central role in intracellular membrane trafficking and organelle maturation. This complex is essential for proper cargo sorting and the generation of specialized organelles such as melanosomes, platelet dense granules, and lysosomes. Notably, HPS4 within BLOC‐3 acts to regulate the localization and activation of specific Rab GTPases—including Rab32 and Rab38—by functioning as a guanine nucleotide exchange factor; such activity is critical for ensuring that vesicular cargo is appropriately delivered to maturing melanosomes and related organelles."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, studies have demonstrated that the physical and functional association between HPS4 and HPS1 is indispensable for maintaining the stability of BLOC‐3, as loss of either subunit disrupts the proper subcellular localization of late endosomes and lysosomes, leading to deficits in pigment formation and other clinical manifestations observed in Hermansky–Pudlak syndrome."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": " In addition, further biochemical studies reveal that HPS4-containing complexes may also be organized into larger modular assemblies (BLOC‐3 and BLOC‐4) that are critical for effective cargo trafficking to newly formed lysosome‐related organelles."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Overall, the function of HPS4 as part of BLOC‐3 underscores its pivotal role in the regulation of endosomal trafficking pathways, with its impairment resulting in the mislocalization of key Rab GTPases, defective melanosome biogenesis, and the consequent clinical features of hypopigmentation, bleeding diathesis, and pulmonary fibrosis associated with Hermansky–Pudlak syndrome."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}, {"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Andreas Gerondopoulos, Lars Langemeyer, Jin-Rui Liang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BLOC-3 mutated in Hermansky-Pudlak syndrome is a Rab32/38 guanine nucleotide exchange factor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Biol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cub.2012.09.020"}], "href": "https://doi.org/10.1016/j.cub.2012.09.020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23084991"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23084991"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Daniel P Kloer, Raul Rojas, Viorica Ivan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Assembly of the biogenesis of lysosome-related organelles complex-3 (BLOC-3) and its interaction with Rab9."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.069088"}], "href": "https://doi.org/10.1074/jbc.M109.069088"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20048159"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20048159"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Tamio Suzuki, Wei Li, Qing Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hermansky-Pudlak syndrome is caused by mutations in HPS4, the human homolog of the mouse light-ear gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng835"}], "href": "https://doi.org/10.1038/ng835"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11836498"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11836498"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ramin Nazarian, Juan M Falcón-Pérez, Esteban C Dell'Angelica "}, {"type": "b", "children": [{"type": "t", "text": "Biogenesis of lysosome-related organelles complex 3 (BLOC-3): a complex containing the Hermansky-Pudlak syndrome (HPS) proteins HPS1 and HPS4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1532040100"}], "href": "https://doi.org/10.1073/pnas.1532040100"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12847290"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12847290"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "José A Martina, Kengo Moriyama, Juan S Bonifacino "}, {"type": "b", "children": [{"type": "t", "text": "BLOC-3, a protein complex containing the Hermansky-Pudlak syndrome gene products HPS1 and HPS4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M301294200"}], "href": "https://doi.org/10.1074/jbc.M301294200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12756248"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12756248"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Pei-Wen Chiang, Naoki Oiso, Rashi Gautam, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Hermansky-Pudlak syndrome 1 (HPS1) and HPS4 proteins are components of two complexes, BLOC-3 and BLOC-4, involved in the biogenesis of lysosome-related organelles."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M300090200"}], "href": "https://doi.org/10.1074/jbc.M300090200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12663659"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12663659"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Paul D Anderson, Marjan Huizing, David A Claassen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hermansky-Pudlak syndrome type 4 (HPS-4): clinical and molecular characteristics."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Genet (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00439-003-0933-5"}], "href": "https://doi.org/10.1007/s00439-003-0933-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12664304"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12664304"}]}]}]}
Synonyms	BLOC3S2
Proteins	HPS4_HUMAN
NCBI Gene ID	89781
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

HPS4 has 5,852 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 123 datasets.

Click the + buttons to view associations for HPS4 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

HPS4 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of HPS4 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of HPS4 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of HPS4 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of HPS4 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of HPS4 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of HPS4 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of HPS4 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of HPS4 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of HPS4 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of HPS4 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of HPS4 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of HPS4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with HPS4 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with HPS4 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of HPS4 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of HPS4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of HPS4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with HPS4 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with HPS4 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of HPS4 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing HPS4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing HPS4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing HPS4 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing HPS4 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with HPS4 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with HPS4 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing HPS4 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of HPS4 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with HPS4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with HPS4 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with HPS4 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of HPS4 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by HPS4 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving HPS4 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving HPS4 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with HPS4 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with HPS4 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with HPS4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with HPS4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at HPS4 gene from the ENCODE Histone Modification Site Profiles dataset.