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 vari... See more...

Aliases for HPS4 Gene

Aliases for HPS4 Gene

  • HPS4 Biogenesis Of Lysosomal Organelles Complex 3 Subunit 2 2 3 5
  • Hermansky-Pudlak Syndrome 4 Protein 3 4
  • Light-Ear Protein Homolog 3 4
  • KIAA1667 2 4
  • BLOC3S2 2 3
  • LE 2 3
  • Hermansky-Pudlak Syndrome 4 2
  • HPS4 5

External Ids for HPS4 Gene

Previous GeneCards Identifiers for HPS4 Gene

  • GC22M023544
  • GC22M025172
  • GC22M025177
  • GC22M026840
  • GC22M009795

Summaries for HPS4 Gene

Entrez Gene Summary for HPS4 Gene

  • 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]

GeneCards Summary for HPS4 Gene

HPS4 (HPS4 Biogenesis Of Lysosomal Organelles Complex 3 Subunit 2) is a Protein Coding gene. Diseases associated with HPS4 include Hermansky-Pudlak Syndrome 4 and Hermansky-Pudlak Syndrome With Pulmonary Fibrosis. Among its related pathways are RAB GEFs exchange GTP for GDP on RABs and Vesicle-mediated transport. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and protein dimerization activity.

UniProtKB/Swiss-Prot Summary for HPS4 Gene

  • Component of the BLOC-3 complex, a complex that acts as a guanine exchange factor (GEF) for RAB32 and RAB38, promotes the exchange of GDP to GTP, converting them from an inactive GDP-bound form into an active GTP-bound form. The BLOC-3 complex plays an important role in the control of melanin production and melanosome biogenesis and promotes the membrane localization of RAB32 and RAB38 (PubMed:23084991).

Gene Wiki entry for HPS4 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for HPS4 Gene

Genomics for HPS4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for HPS4 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around HPS4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for HPS4

Top Transcription factor binding sites by QIAGEN in the HPS4 gene promoter:
  • COUP
  • COUP-TF
  • COUP-TF1
  • HNF-4alpha1
  • HNF-4alpha2
  • STAT3

Genomic Locations for HPS4 Gene

Genomic Locations for HPS4 Gene
chr22:26,443,109-26,483,863
(GRCh38/hg38)
Size:
40,755 bases
Orientation:
Minus strand
chr22:26,839,389-26,879,820
(GRCh37/hg19)
Size:
40,432 bases
Orientation:
Minus strand

Genomic View for HPS4 Gene

Genes around HPS4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
HPS4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for HPS4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for HPS4 Gene

Proteins for HPS4 Gene

  • Protein details for HPS4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9NQG7-HPS4_HUMAN
    Recommended name:
    Hermansky-Pudlak syndrome 4 protein
    Protein Accession:
    Q9NQG7
    Secondary Accessions:
    • B1AHQ4
    • Q5H8V6
    • Q96LX6
    • Q9BY93
    • Q9UH37
    • Q9UH38

    Protein attributes for HPS4 Gene

    Size:
    708 amino acids
    Molecular mass:
    76919 Da
    Quaternary structure:
    • Component of the biogenesis of lysosome-related organelles complex-3 (or BLOC-3), a heterodimer of HPS1 and HPS4 (PubMed:20048159, PubMed:23084991). HPS4 and the BLOC-3 complex interact with the GTP-bound form of RAB9A and RAB9B but not with the GDP-bound form of RAB9A and RAB9B. The BLOC-3 complex does not interact with RAB5A, RAB7A and RAB27A (PubMed:20048159).
    SequenceCaution:
    • Sequence=BAB33337.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=BAB33337.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305}; Sequence=BC035614; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};

    Alternative splice isoforms for HPS4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for HPS4 Gene

Post-translational modifications for HPS4 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for HPS4 Gene

Domains & Families for HPS4 Gene

Gene Families for HPS4 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted intracellular proteins

Protein Domains for HPS4 Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for HPS4 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ77277, highly similar to Homo sapiens Hermansky-Pudlak syndrome 4 (HPS4), transcript variant 1, mRNA (A8K2E6_HUMAN)
  • Light-ear protein homolog (HPS4_HUMAN)
  • Hermansky-Pudlak syndrome 4 (Q6P1K3_HUMAN)
genes like me logo Genes that share domains with HPS4: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for HPS4 Gene

Function for HPS4 Gene

Molecular function for HPS4 Gene

UniProtKB/Swiss-Prot Function:
Component of the BLOC-3 complex, a complex that acts as a guanine exchange factor (GEF) for RAB32 and RAB38, promotes the exchange of GDP to GTP, converting them from an inactive GDP-bound form into an active GTP-bound form. The BLOC-3 complex plays an important role in the control of melanin production and melanosome biogenesis and promotes the membrane localization of RAB32 and RAB38 (PubMed:23084991).

Phenotypes From GWAS Catalog for HPS4 Gene

Gene Ontology (GO) - Molecular Function for HPS4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005085 contributes_to guanyl-nucleotide exchange factor activity IEA,IDA 23084991
GO:0005515 protein binding IPI 12756248
GO:0017137 Rab GTPase binding IPI 20048159
GO:0042803 protein homodimerization activity IPI 12663659
GO:0046983 protein dimerization activity IPI 12663659
genes like me logo Genes that share ontologies with HPS4: view
genes like me logo Genes that share phenotypes with HPS4: view

Human Phenotype Ontology for HPS4 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for HPS4

No data available for Enzyme Numbers (IUBMB) , Animal Models , Transcription Factor Targets and HOMER Transcription for HPS4 Gene

Localization for HPS4 Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for HPS4 gene
Compartment Confidence
cytosol 5
lysosome 5
nucleus 3
cytoskeleton 2
endosome 2
plasma membrane 1
extracellular 1
endoplasmic reticulum 1
golgi apparatus 1
peroxisome 0

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for HPS4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IDA 12756248
GO:0005764 lysosome IDA 12663659
GO:0005765 lysosomal membrane IBA 21873635
GO:0005829 cytosol TAS --
GO:0016020 membrane IDA 12756248
genes like me logo Genes that share ontologies with HPS4: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for HPS4 Gene

Pathways & Interactions for HPS4 Gene

genes like me logo Genes that share pathways with HPS4: view

Pathways by source for HPS4 Gene

Gene Ontology (GO) - Biological Process for HPS4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006605 protein targeting IDA 12663659
GO:0006996 organelle organization IEA --
GO:0007040 lysosome organization IDA 12663659
GO:0007596 blood coagulation IEA --
GO:0007599 hemostasis TAS 11836498
genes like me logo Genes that share ontologies with HPS4: view

No data available for SIGNOR curated interactions for HPS4 Gene

Drugs & Compounds for HPS4 Gene

No Compound Related Data Available

Transcripts for HPS4 Gene

mRNA/cDNA for HPS4 Gene

14 REFSEQ mRNAs :
18 NCBI additional mRNA sequence :
18 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for HPS4

Alternative Splicing Database (ASD) splice patterns (SP) for HPS4 Gene

ExUns: 1a · 1b · 1c · 1d · 1e · 1f · 1g ^ 2 ^ 3a · 3b · 3c ^ 4a · 4b · 4c · 4d · 4e · 4f ^ 5 ^ 6a · 6b ^ 7a · 7b ^ 8 ^ 9 ^ 10 ^ 11 ^
SP1: - -
SP2: - -
SP3:
SP4: - -
SP5: - -
SP6: -
SP7: - - - - - -
SP8:
SP9: - -
SP10: - - - - -
SP11: - - - -
SP12:

ExUns: 12 ^ 13 ^ 14a · 14b ^ 15 ^ 16 ^ 17 ^ 18 ^ 19a · 19b · 19c ^ 20
SP1: - -
SP2:
SP3: -
SP4: - - -
SP5: - - - -
SP6:
SP7:
SP8:
SP9:
SP10:
SP11:
SP12: - -

Relevant External Links for HPS4 Gene

GeneLoc Exon Structure for
HPS4

Expression for HPS4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for HPS4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for HPS4 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (50.3) and CD4 Tcells (14.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for HPS4 Gene



Protein tissue co-expression partners for HPS4 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for HPS4

SOURCE GeneReport for Unigene cluster for HPS4 Gene:

Hs.474436

Evidence on tissue expression from TISSUES for HPS4 Gene

  • Nervous system(4.7)
  • Blood(4.4)
  • Liver(4.3)
  • Skin(2.5)
  • Lung(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for HPS4 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • immune
  • integumentary
  • nervous
  • respiratory
  • urinary
Regions:
Head and neck:
  • brain
  • cranial nerve
  • ear
  • eye
  • face
  • head
  • mouth
  • nose
Thorax:
  • heart
  • heart valve
  • lung
Abdomen:
  • intestine
  • kidney
  • large intestine
  • small intestine
Pelvis:
  • anus
  • ureter
  • urinary bladder
General:
  • blood
  • blood vessel
  • coagulation system
  • hair
  • peripheral nervous system
  • skin
genes like me logo Genes that share expression patterns with HPS4: view

No data available for mRNA differential expression in normal tissues and mRNA Expression by UniProt/SwissProt for HPS4 Gene

Orthologs for HPS4 Gene

This gene was present in the common ancestor of animals.

Orthologs for HPS4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia HPS4 30 31
  • 99.01 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia HPS4 30 31
  • 78.24 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia HPS4 30 31
  • 75.61 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Hps4 30 17 31
  • 72.26 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Hps4 30
  • 68.59 (n)
Oppossum
(Monodelphis domestica)
Mammalia HPS4 31
  • 56 (a)
OneToOne
Chicken
(Gallus gallus)
Aves HPS4 30 31
  • 70.3 (n)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia hps4 30
  • 60.8 (n)
Zebrafish
(Danio rerio)
Actinopterygii hps4 31
  • 37 (a)
OneToOne
-- 30
Fruit Fly
(Drosophila melanogaster)
Insecta HPS4 31
  • 16 (a)
OneToOne
Species where no ortholog for HPS4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Lizard (Anolis carolinensis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for HPS4 Gene

ENSEMBL:
Gene Tree for HPS4 (if available)
TreeFam:
Gene Tree for HPS4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for HPS4: view image

Paralogs for HPS4 Gene

(1) SIMAP similar genes for HPS4 Gene using alignment to 7 proteins:

  • HPS4_HUMAN
  • A8K2E6_HUMAN
  • E5RG08_HUMAN
  • F1LLU8_HUMAN
  • F8VYA9_HUMAN
  • F8WC53_HUMAN
  • Q6P1K3_HUMAN
genes like me logo Genes that share paralogs with HPS4: view

No data available for Paralogs for HPS4 Gene

Variants for HPS4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for HPS4 Gene

SNP ID Clinical significance and condition Chr 22 pos Variation AA Info Type
666701 Likely Benign: not specified; not provided 26,472,896(-) C/A MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT
690343 Likely Pathogenic: Hermansky-Pudlak syndrome 26,476,988(-) C/T INTRON_VARIANT
708993 Conflicting Interpretations: Hermansky-Pudlak syndrome 4; not provided 26,466,228(-) T/C MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT
723870 Benign: not provided 26,465,517(-) A/G NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT
725698 Conflicting Interpretations: Hermansky-Pudlak syndrome 4; not provided 26,466,218(-) C/G INTRON_VARIANT

Additional dbSNP identifiers (rs#s) for HPS4 Gene

Structural Variations from Database of Genomic Variants (DGV) for HPS4 Gene

Variant ID Type Subtype PubMed ID
nsv519472 CNV loss 19592680
nsv7350 OTHER inversion 18451855

Variation tolerance for HPS4 Gene

Residual Variation Intolerance Score: 73.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.20; 69.77% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for HPS4 Gene

Human Gene Mutation Database (HGMD)
HPS4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
HPS4

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for HPS4 Gene

Disorders for HPS4 Gene

MalaCards: The human disease database

(14) MalaCards diseases for HPS4 Gene - From: OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
hermansky-pudlak syndrome 4
  • albinism with hemorrhagic diathesis and pigmented reticuloendothelial cells
hermansky-pudlak syndrome with pulmonary fibrosis
  • hps with pulmonary fibrosis
hermansky-pudlak syndrome
  • albinism with hemorrhagic diathesis and pigmented reticuloendothelial cells
oculocutaneous albinism
  • albinism, oculocutaneous
albinism
- elite association - COSMIC cancer census association via MalaCards
Search HPS4 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

HPS4_HUMAN
  • Hermansky-Pudlak syndrome 4 (HPS4) [MIM:614073]: 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. {ECO:0000269 PubMed:11836498}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for HPS4

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with HPS4: view

No data available for Genatlas for HPS4 Gene

Publications for HPS4 Gene

  1. Hermansky-Pudlak syndrome is caused by mutations in HPS4, the human homolog of the mouse light-ear gene. (PMID: 11836498) Suzuki T … Spritz RA (Nature genetics 2002) 2 3 4 23
  2. Comprehensive analysis of oculocutaneous albinism among non-Hispanic caucasians shows that OCA1 is the most prevalent OCA type. (PMID: 18463683) Hutton SM … Spritz RA (The Journal of investigative dermatology 2008) 3 23 41
  3. BLOC-3 mutated in Hermansky-Pudlak syndrome is a Rab32/38 guanine nucleotide exchange factor. (PMID: 23084991) Gerondopoulos A … Barr FA (Current biology : CB 2012) 3 4
  4. Assembly of the biogenesis of lysosome-related organelles complex-3 (BLOC-3) and its interaction with Rab9. (PMID: 20048159) Kloer DP … Bonifacino JS (The Journal of biological chemistry 2010) 3 4
  5. Intestinal disease in Hermansky-Pudlak syndrome: occurrence of colitis and relation to genotype. (PMID: 16431308) Hussain N … Mannon P (Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 2006) 3 41

Products for HPS4 Gene

Sources for HPS4 Gene