Seroatlas · Human Serome Atlas

ZNRF4

E3 ubiquitin-protein ligase ZNRF4

Also known as: RNF204, spzn, Ssrzf1, ZNRF4_HUMAN

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

Protein identityUniProt · HPA

UniProt accession
Q8WWF5
Gene
ZNRF4
Ensembl
ENSG00000105428
Chromosome
19
Canonical length
429 aa
Protein class
Enzymes, Predicted membrane proteins

OverviewNCBI Gene

Enables ubiquitin protein ligase activity. Involved in negative regulation of nucleotide-binding activity oligomerization domain containing 2 signaling pathway and proteasome-mediated ubiquitin-dependent protein catabolic process. Is active in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Jul 2025]

Canonical amino-acid sequenceUniProt

429 residues, UniProt reviewed canonical sequence.

>Q8WWF5|ZNRF4
     1  MPLCRPEHLM PRASRVPVAA SLPLSHAVIP TQLPSRPGHR PPGRPRRCPK ASCLPPPVGP
    61  SSTQTAKRVT MGWPRPGRAL VAVKALLVLS LLQVPAQAVV RAVLEDNSSS VDFADLPALF
   121  GVPLAPEGIR GYLMEVKPAN ACHPIEAPRL GNRSLGAIVL IRRYDCTFDL KVLNAQRAGF
   181  EAAIVHNVHS DDLVSMTHVY EDLRGQIAIP SVFVSEAASQ DLRVILGCNK SAHALLLPDD
   241  PPCHDLGCHP VLTVSWVLGC TLALVVSAFF VLNHLWLWAQ ACCSHRRPVK TSTCQKAQVR
   301  TFTWHNDLCA ICLDEYEEGD QLKILPCSHT YHCKCIDPWF SQAPRRSCPV CKQSVAATED
   361  SFDSTTYSFR DEDPSLPGHR PPIWAIQVQL RSRRLELLGR ASPHCHCSTT SLEAEYTTVS
   421  SAPPEAPGQ

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ZNRF4 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
1
Mean surface accessibility (rSASA)
0.47
Highest tissue expression
113 nTPM

Expression across tissuesHPA

Tissue

  • testis: 113 nTPM
  • amygdala: 0.2 nTPM
  • cerebral cortex: 0.1 nTPM
  • hippocampal formation: 0.1 nTPM
  • hypothalamus: 0.1 nTPM
  • adipose tissue: 0 nTPM

Single-cell type

  • late spermatids: 841 nCPM
  • early spermatids: 694 nCPM
  • late primary spermatocytes: 277 nCPM
  • leydig cells: 2.9 nCPM
  • undifferentiated spermatogonia: 1.5 nCPM
  • differentiating spermatogonia: 1.2 nCPM

Immune cell

  • basophil: 0 nTPM
  • classical monocyte: 0 nTPM
  • eosinophil: 0 nTPM
  • gdT-cell: 0 nTPM
  • intermediate monocyte: 0 nTPM
  • MAIT T-cell: 0 nTPM

Brain region

  • amygdala: 0.3 nTPM
  • cerebral cortex: 0.3 nTPM
  • hypothalamus: 0.3 nTPM
  • basal ganglia: 0.2 nTPM
  • hippocampal formation: 0.2 nTPM
  • midbrain: 0.2 nTPM

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)
1.42
gnomAD pLI
0.49
gnomAD missense Z
0.24
DepMap mean gene effect
0.11
DepMap dependency class
none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% 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 ZNRF4 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 ZNRF4 as an antibody target. Whether an autoantibody or antibody against ZNRF4 could matter depends on whether native ZNRF4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

ZNRF4 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 ZNRF4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/ZNRF4. 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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