Seroatlas · Human Serome Atlas

ROBO4

Roundabout homolog 4

Also known as: ECSM4, FLJ20798, MRB, ROBO4_HUMAN

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

Protein identityUniProt · HPA

UniProt accession
Q8WZ75
Gene
ROBO4
Ensembl
ENSG00000154133
Chromosome
11
Canonical length
1007 aa
Protein class
Disease related genes, Human disease related genes, Plasma proteins, Predicted membrane proteins
Subcellular location
Plasma membrane

OverviewNCBI Gene

Predicted to enable cell-cell adhesion mediator activity. Involved in establishment of endothelial barrier. Located in extracellular exosome. Implicated in aortic valve disease 3. Biomarker of pre-eclampsia and thyroid gland carcinoma. [provided by Alliance of Genome Resources, Jul 2025]

Canonical amino-acid sequenceUniProt

1007 residues, UniProt reviewed canonical sequence.

>Q8WZ75|ROBO4
     1  MGSGGDSLLG GRGSLPLLLL LIMGGMAQDS PPQILVHPQD QLFQGPGPAR MSCQASGQPP
    61  PTIRWLLNGQ PLSMVPPDPH HLLPDGTLLL LQPPARGHAH DGQALSTDLG VYTCEASNRL
   121  GTAVSRGARL SVAVLREDFQ IQPRDMVAVV GEQFTLECGP PWGHPEPTVS WWKDGKPLAL
   181  QPGRHTVSGG SLLMARAEKS DEGTYMCVAT NSAGHRESRA ARVSIQEPQD YTEPVELLAV
   241  RIQLENVTLL NPDPAEGPKP RPAVWLSWKV SGPAAPAQSY TALFRTQTAP GGQGAPWAEE
   301  LLAGWQSAEL GGLHWGQDYE FKVRPSSGRA RGPDSNVLLL RLPEKVPSAP PQEVTLKPGN
   361  GTVFVSWVPP PAENHNGIIR GYQVWSLGNT SLPPANWTVV GEQTQLEIAT HMPGSYCVQV
   421  AAVTGAGAGE PSRPVCLLLE QAMERATQEP SEHGPWTLEQ LRATLKRPEV IATCGVALWL
   481  LLLGTAVCIH RRRRARVHLG PGLYRYTSED AILKHRMDHS DSQWLADTWR STSGSRDLSS
   541  SSSLSSRLGA DARDPLDCRR SLLSWDSRSP GVPLLPDTST FYGSLIAELP SSTPARPSPQ
   601  VPAVRRLPPQ LAQLSSPCSS SDSLCSRRGL SSPRLSLAPA EAWKAKKKQE LQHANSSPLL
   661  RGSHSLELRA CELGNRGSKN LSQSPGAVPQ ALVAWRALGP KLLSSSNELV TRHLPPAPLF
   721  PHETPPTQSQ QTQPPVAPQA PSSILLPAAP IPILSPCSPP SPQASSLSGP SPASSRLSSS
   781  SLSSLGEDQD SVLTPEEVAL CLELSEGEET PRNSVSPMPR APSPPTTYGY ISVPTASEFT
   841  DMGRTGGGVG PKGGVLLCPP RPCLTPTPSE GSLANGWGSA SEDNAASARA SLVSSSDGSF
   901  LADAHFARAL AVAVDSFGFG LEPREADCVF IDASSPPSPR DEIFLTPNLS LPLWEWRPDW
   961  LEDMEVSHTQ RLGRGMPPWP PDSQISSQRS QLHCRMPKAG ASPVDYS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ROBO4 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
Cell surface
Secreted
No
Transmembrane segments
0
Mean surface accessibility (rSASA)
0.55
Highest tissue expression
47 nTPM

Expression across tissuesHPA

Tissue

  • spleen: 47 nTPM
  • adipose tissue: 42 nTPM
  • lung: 37 nTPM
  • breast: 34 nTPM
  • heart muscle: 29 nTPM
  • placenta: 27 nTPM

Single-cell type

  • lymphatic endothelial cells: 132 nCPM
  • vascular endothelial cells: 131 nCPM
  • hematopoietic stem cells: 36 nCPM
  • mesothelial cells: 14 nCPM
  • epicardial cells: 11 nCPM
  • adrenal medulla cells: 11 nCPM

Immune cell

  • myeloid DC: 0.1 nTPM
  • basophil: 0 nTPM
  • classical monocyte: 0 nTPM
  • eosinophil: 0 nTPM
  • gdT-cell: 0 nTPM
  • intermediate monocyte: 0 nTPM

Brain region

  • thalamus: 20 nTPM
  • medulla oblongata: 16 nTPM
  • amygdala: 16 nTPM
  • pons: 16 nTPM
  • midbrain: 15 nTPM
  • basal ganglia: 12 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ROBO4.

Disease | AllUniProt

Conditions ROBO4 is implicated in, by any mechanism.

Disease | GeneticClinVar

15 pathogenic / likely-pathogenic of 310 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

  • Bicuspid aortic valve
  • Ascending tubular aorta aneurysm
  • Aortic valve disease 3
  • Thoracic aortic aneurysm
  • ROBO4-related disorder

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)
0.91
gnomAD pLI
0
gnomAD missense Z
0.09
DepMap mean gene effect
0.06
DepMap dependency class
selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of ROBO4 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 ROBO4 as an antibody target. Whether an autoantibody or antibody against ROBO4 could matter depends on whether native ROBO4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

ROBO4 is annotated at the cell surface, where native ROBO4 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Annotation status

The present source text does not explicitly label ROBO4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/ROBO4. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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