Seroatlas · Human Serome Atlas

HPS4

BLOC-3 complex member HPS4

Also known as: BLOC3S2, HPS4_HUMAN, KIAA1667, LE

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: Q9NQG7
Gene: HPS4
Ensembl: ENSG00000100099
Chromosome: 22
Canonical length: 708 aa
Protein class: Disease related genes, Human disease related genes, Predicted intracellular proteins
Subcellular location: Plasma membrane

OverviewNCBI 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]

Canonical amino-acid sequenceUniProt

708 residues, UniProt reviewed canonical sequence.

>Q9NQG7|HPS4
     1  MATSTSTEAK SASWWNYFFL YDGSKVKEEG DPTRAGICYF YPSQTLLDQQ ELLCGQIAGV
    61  VRCVSDISDS PPTLVRLRKL KFAIKVDGDY LWVLGCAVEL PDVSCKRFLD QLVGFFNFYN
   121  GPVSLAYENC SQEELSTEWD TFIEQILKNT SDLHKIFNSL WNLDQTKVEP LLLLKAARIL
   181  QTCQRSPHIL AGCILYKGLI VSTQLPPSLT AKVLLHRTAP QEQRLPTGED APQEHGAALP
   241  PNVQIIPVFV TKEEAISLHE FPVEQMTRSL ASPAGLQDGS AQHHPKGGST SALKENATGH
   301  VESMAWTTPD PTSPDEACPD GRKENGCLSG HDLESIRPAG LHNSARGEVL GLSSSLGKEL
   361  VFLQEELDLS EIHIPEAQEV EMASGHFAFL HVPVPDGRAP YCKASLSASS SLEPTPPEDT
   421  AISSLRPPSA PEMLTQHGAQ EQLEDHPGHS SQAPIPRADP LPRRTRRPLL LPRLDPGQRG
   481  NKLPTGEQGL DEDVDGVCES HAAPGLECSS GSANCQGAGP SADGISSRLT PAESCMGLVR
   541  MNLYTHCVKG LVLSLLAEEP LLGDSAAIEE VYHSSLASLN GLEVHLKETL PRDEAASTSS
   601  TYNFTHYDRI QSLLMANLPQ VATPQDRRFL QAVSLMHSEF AQLPALYEMT VRNASTAVYA
   661  CCNPIQETYF QQLAPAARSS GFPNPQDGAF SLSGKAKQKL LKHGVNLL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HPS4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Other membrane
Secreted: No
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.47
Highest tissue expression: 22 nTPM

Expression across tissuesHPA

Tissue

cerebellum: 22 nTPM
skin: 14 nTPM
testis: 13 nTPM
basal ganglia: 12 nTPM
pancreas: 11 nTPM
thymus: 11 nTPM

Single-cell type

sertoli cells: 129 nCPM
melanocytes: 104 nCPM
erythrocyte progenitors: 97 nCPM
undifferentiated spermatogonia: 82 nCPM
rod photoreceptor cells: 74 nCPM
retinal pigment epithelial cells: 68 nCPM

Immune cell

basophil: 7 nTPM
NK-cell: 6.4 nTPM
memory B-cell: 4.4 nTPM
total PBMC: 3.9 nTPM
gdT-cell: 3.8 nTPM
myeloid DC: 3.7 nTPM

Brain region

thalamus: 12 nTPM
midbrain: 11 nTPM
choroid plexus: 10 nTPM
hypothalamus: 10 nTPM
spinal cord: 10 nTPM
amygdala: 9.8 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about HPS4.

Disease | AllUniProt

Conditions HPS4 is implicated in, by any mechanism.

Hermansky-Pudlak syndrome 4 (HPS4) MIM:614073

Disease | GeneticClinVar

91 pathogenic / likely-pathogenic of 940 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Hermansky-Pudlak syndrome 4
Hermansky-Pudlak syndrome
Melanoma
See cases

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.63
gnomAD pLI: 0
gnomAD missense Z: -0.8
DepMap mean gene effect: 0.04
DepMap dependency class: none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

blood coagulation
hemostasis
lysosome organization
melanocyte differentiation
melanosome assembly
platelet dense granule organization
positive regulation of protein targeting to mitochondrion
protein stabilization
protein targeting
vesicle-mediated transport
positive regulation of eye pigmentation

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

CCZ1/INTU/HSP4, first Longin domain
CCZ1/INTU/HPS4, third Longin domain
First Longin domain of INTU, CCZ1 and HPS4
Intu longin-like domain 3
BLOC-3 complex member HPS4

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of HPS4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads HPS4 as an antibody target. Whether an autoantibody or antibody against HPS4 could matter depends on whether native HPS4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

HPS4 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label HPS4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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