Seroatlas · Human Serome Atlas

SIX3

Homeobox protein SIX3

Also known as: HPE2, SIX3_HUMAN

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

Protein identityUniProt · HPA

UniProt accession
O95343
Gene
SIX3
Ensembl
ENSG00000138083
Chromosome
2
Canonical length
332 aa
Protein class
Disease related genes, Human disease related genes, Predicted intracellular proteins, Transcription factors
Subcellular location
Nucleoplasm

OverviewNCBI Gene

This gene encodes a member of the sine oculis homeobox transcription factor family. The encoded protein plays a role in eye development. Mutations in this gene have been associated with holoprosencephaly type 2. [provided by RefSeq, Oct 2009]

Canonical amino-acid sequenceUniProt

332 residues, UniProt reviewed canonical sequence.

>O95343|SIX3
     1  MVFRSPLDLY SSHFLLPNFA DSHHRSILLA SSGGGNGAGG GGGAGGGSGG GNGAGGGGAG
    61  GAGGGGGGGS RAPPEELSMF QLPTLNFSPE QVASVCETLE ETGDIERLGR FLWSLPVAPG
   121  ACEAINKHES ILRARAVVAF HTGNFRDLYH ILENHKFTKE SHGKLQAMWL EAHYQEAEKL
   181  RGRPLGPVDK YRVRKKFPLP RTIWDGEQKT HCFKERTRSL LREWYLQDPY PNPSKKRELA
   241  QATGLTPTQV GNWFKNRRQR DRAAAAKNRL QHQAIGPSGM RSLAEPGCPT HGSAESPSTA
   301  ASPTTSVSSL TERADTGTSI LSVTSSDSEC DV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SIX3 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
Intracellular
Secreted
No
Transmembrane segments
0
Mean surface accessibility (rSASA)
0.52
Highest tissue expression
37 nTPM

Expression across tissuesHPA

Tissue

  • basal ganglia: 37 nTPM
  • pituitary gland: 25 nTPM
  • retina: 24 nTPM
  • hypothalamus: 14 nTPM
  • choroid plexus: 10 nTPM
  • parathyroid gland: 8.6 nTPM

Single-cell type

  • müller glia: 329 nCPM
  • retinal pigment epithelial cells: 222 nCPM
  • pituicytes/fscs: 184 nCPM
  • retinal bipolar cells: 116 nCPM
  • retinal amacrine cells: 115 nCPM
  • retinal horizontal cells: 106 nCPM

Immune cell

  • basophil: 1.4 nTPM
  • non-classical monocyte: 0.5 nTPM
  • neutrophil: 0.4 nTPM
  • eosinophil: 0.3 nTPM
  • MAIT T-cell: 0.3 nTPM
  • NK-cell: 0.3 nTPM

Brain region

  • basal ganglia: 47 nTPM
  • hypothalamus: 38 nTPM
  • choroid plexus: 26 nTPM
  • cerebral cortex: 26 nTPM
  • amygdala: 17 nTPM
  • thalamus: 12 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SIX3.

Disease | AllUniProt

Conditions SIX3 is implicated in, by any mechanism.

Disease | GeneticClinVar

34 pathogenic / likely-pathogenic of 268 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

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)
0.32
gnomAD pLI
0.95
gnomAD missense Z
2.07
DepMap mean gene effect
-0.01
DepMap dependency class
selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% 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 SIX3 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 SIX3 as an antibody target. Whether an autoantibody or antibody against SIX3 could matter depends on whether native SIX3 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

SIX3 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 SIX3 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/SIX3. 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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