Seroatlas · Human Serome Atlas

ZC4H2

Zinc finger C4H2 domain-containing protein

Also known as: HCA127, KIAA1166, MCS, MRXS4, WWS, ZC4H2_HUMAN

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

Protein identityUniProt · HPA

UniProt accession
Q9NQZ6
Gene
ZC4H2
Ensembl
ENSG00000126970
Chromosome
X
Canonical length
224 aa
Protein class
Disease related genes, Human disease related genes, Predicted intracellular proteins
Subcellular location
Vesicles,Microtubules,Primary cilium,Basal body

OverviewNCBI Gene

This gene encodes a member of the zinc finger domain-containing protein family. This family member has a C-terminal zinc finger domain that is characterized by four cysteine residues and two histidine residues, and it also includes a coiled-coil region. This protein has been detected as an autoantigen in hepatocellular carcinoma patients. This gene has been identified as a potential candidate for X-linked cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

Canonical amino-acid sequenceUniProt

224 residues, UniProt reviewed canonical sequence.

>Q9NQZ6|ZC4H2
     1  MADEQEIMCK LESIKEIRNK TLQMEKIKAR LKAEFEALES EERHLKEYKQ EMDLLLQEKM
    61  AHVEELRLIH ADINVMENTI KQSENDLNKL LESTRRLHDE YKPLKEHVDA LRMTLGLQRL
   121  PDLCEEEEKL SLDYFEKQKA EWQTEPQEPP IPESLAAAAA AAQQLQVARK QDTRQTATFR
   181  QQPPPMKACL SCHQQIHRNA PICPLCKAKS RSRNPKKPKR KQDE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ZC4H2 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)
0.49
Highest tissue expression
11 nTPM

Expression across tissuesHPA

Tissue

  • parathyroid gland: 11 nTPM
  • hypothalamus: 8.5 nTPM
  • colon: 8.1 nTPM
  • ovary: 7.9 nTPM
  • pituitary gland: 7.8 nTPM
  • spinal cord: 7.3 nTPM

Single-cell type

  • choroid plexus epithelial cells: 191 nCPM
  • gonadotrophs: 130 nCPM
  • cone photoreceptor cells: 126 nCPM
  • somatotrophs: 125 nCPM
  • lactotrophs: 116 nCPM
  • corticotrophs: 108 nCPM

Immune cell

  • naive CD4 T-cell: 2.8 nTPM
  • MAIT T-cell: 1.8 nTPM
  • plasmacytoid DC: 1.7 nTPM
  • memory CD4 T-cell: 1.6 nTPM
  • memory B-cell: 1.5 nTPM
  • naive CD8 T-cell: 1.2 nTPM

Brain region

  • medulla oblongata: 8 nTPM
  • hypothalamus: 7.8 nTPM
  • pons: 7.7 nTPM
  • midbrain: 7.2 nTPM
  • white matter: 7.2 nTPM
  • spinal cord: 6.8 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ZC4H2.

Disease | AllUniProt

Conditions ZC4H2 is implicated in, by any mechanism.

  • Wieacker-Wolf syndrome (WRWF) MIM:314580
  • Wieacker-Wolff syndrome, female-restricted (WRWFFR) MIM:301041

Disease | GeneticClinVar

68 pathogenic / likely-pathogenic of 254 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)
0.39
gnomAD pLI
0.91
gnomAD missense Z
1.51
DepMap mean gene effect
0.13
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

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

  • Zinc finger C4H2 domain-containing protein
  • Zinc finger C4H2-type
  • Zinc finger-containing protein

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of ZC4H2 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 ZC4H2 as an antibody target. Whether an autoantibody or antibody against ZC4H2 could matter depends on whether native ZC4H2 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

ZC4H2 is annotated at the cell surface, where native ZC4H2 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Source-annotated serology context

The source annotations explicitly mention antibody, autoantibody, autoantigen, or autoimmune context. This is biological context, not study-specific reactivity.

  • This protein has been detected as an autoantigen in hepatocellular carcinoma patients.

Canonical record: https://seroatlas.com/gene/ZC4H2. 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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