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 pote... See more...

Aliases for ZC4H2 Gene

Aliases for ZC4H2 Gene

  • Zinc Finger C4H2-Type Containing 2 3 5
  • KIAA1166 2 3 4
  • Miles-Carpenter X-Linked Mental Retardation Syndrome 2 3
  • Hepatocellular Carcinoma-Associated Antigen 127 3 4
  • Zinc Finger C4H2 Domain-Containing Protein 3 4
  • Zinc Finger, C4H2 Domain Containing 2 3
  • HCA127 3 4
  • Miles-Carpenter Syndrome (Mental Retardation, X-Linked, Syndromic-4, With Congenital Contractures And Low Fingertip Arches) 3
  • Wieacker-Wolff Syndrome 2
  • MRXS4 3
  • WRWF 3
  • MCS 3
  • WWS 3

External Ids for ZC4H2 Gene

Previous HGNC Symbols for ZC4H2 Gene

  • KIAA1166
  • WWS
  • MCS
  • MRXS4

Previous GeneCards Identifiers for ZC4H2 Gene

  • GC0XM064053
  • GC0XM057961
  • GC0XM064136

Summaries for ZC4H2 Gene

Entrez Gene Summary for ZC4H2 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]

GeneCards Summary for ZC4H2 Gene

ZC4H2 (Zinc Finger C4H2-Type Containing) is a Protein Coding gene. Diseases associated with ZC4H2 include Wieacker-Wolff Syndrome and Intellectual Disability-Developmental Delay-Contractures Syndrome.

UniProtKB/Swiss-Prot Summary for ZC4H2 Gene

  • Plays a role in interneurons differentiation (PubMed:26056227). Involved in neuronal development and in neuromuscular junction formation.

Gene Wiki entry for ZC4H2 Gene

Additional gene information for ZC4H2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for ZC4H2 Gene

Genomics for ZC4H2 Gene

GeneHancer (GH) Regulatory Elements for ZC4H2 Gene

Promoters and enhancers for ZC4H2 Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH0XJ065034 Promoter/Enhancer 2 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas 752.8 -0.6 -556 2.6 CTCF CSDE1 POLR2A ZFX NCOA6 PRDM1 SP5 EGR1 GMEB1 GLIS2 ZC4H2 ZC3H12B lnc-ZC3H12B-3 ENSG00000217835 MTMR8 AMER1 RF00994-1185
GH0XJ064975 Promoter/Enhancer 1.7 EPDnew Ensembl ENCODE CraniofacialAtlas 753.8 +58.7 58743 2.8 SIX5 HCFC1 ELF1 ZNF652 PRDM1 ZNF143 POLR2A ZBTB20 SCRT2 ZBTB48 ZC4H2 piR-60885-178 lnc-MTMR8-1
GH0XJ065030 Enhancer 0.2 FANTOM5 4.6 +3.9 3887 0.3 ZC4H2 piR-58929-122
GH0XJ065244 Enhancer 0.2 FANTOM5 1.3 -210.1 -210149 0.3 ZC3H12B ZC4H2 CCT4P2 piR-38351-528 lnc-ZC3H12B-18
GH0XJ064928 Enhancer 0.2 FANTOM5 0.1 +106.2 106248 0.1 lnc-MTMR8-1 piR-60885-178 ZC4H2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around ZC4H2 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the ZC4H2 gene promoter:
  • Evi-1
  • GCNF
  • GCNF-1
  • GCNF-2
  • Pax-5
  • POU2F1
  • POU2F1a
  • SRY
  • STAT5A

Genomic Locations for ZC4H2 Gene

Genomic Locations for ZC4H2 Gene
118,943 bases
Minus strand
118,344 bases
Minus strand

Genomic View for ZC4H2 Gene

Genes around ZC4H2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ZC4H2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ZC4H2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ZC4H2 Gene

Proteins for ZC4H2 Gene

  • Protein details for ZC4H2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Zinc finger C4H2 domain-containing protein
    Protein Accession:
    Secondary Accessions:
    • B2RDC2
    • B3KVZ5
    • B4DED0
    • E7EM74
    • G3V1L3
    • Q53H73
    • Q5JTF9
    • Q9H9C3
    • Q9H9H7
    • Q9ULQ4

    Protein attributes for ZC4H2 Gene

    224 amino acids
    Molecular mass:
    26244 Da
    Quaternary structure:
    No Data Available
    • Sequence=BAA86480.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};

    Alternative splice isoforms for ZC4H2 Gene


neXtProt entry for ZC4H2 Gene

Post-translational modifications for ZC4H2 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for ZC4H2 Gene

No data available for DME Specific Peptides for ZC4H2 Gene

Domains & Families for ZC4H2 Gene

Gene Families for ZC4H2 Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted intracellular proteins

Protein Domains for ZC4H2 Gene


Suggested Antigen Peptide Sequences for ZC4H2 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ53717, highly similar to Hepatocellular carcinoma-associated antigen 127 homolog (B4DED0_HUMAN)
  • Hepatocellular carcinoma-associated antigen 127 (ZC4H2_HUMAN)
genes like me logo Genes that share domains with ZC4H2: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for ZC4H2 Gene

Function for ZC4H2 Gene

Molecular function for ZC4H2 Gene

UniProtKB/Swiss-Prot Function:
Plays a role in interneurons differentiation (PubMed:26056227). Involved in neuronal development and in neuromuscular junction formation.

Phenotypes From GWAS Catalog for ZC4H2 Gene

Gene Ontology (GO) - Molecular Function for ZC4H2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 25416956
GO:0046872 metal ion binding IEA --
genes like me logo Genes that share ontologies with ZC4H2: view
genes like me logo Genes that share phenotypes with ZC4H2: view

Human Phenotype Ontology for ZC4H2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

CRISPR Products

Clone Products

No data available for Enzyme Numbers (IUBMB) , Animal Models , Transcription Factor Targets and HOMER Transcription for ZC4H2 Gene

Localization for ZC4H2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ZC4H2 Gene

Cytoplasm. Nucleus. Cell junction, synapse, postsynaptic cell membrane. Note=Upon transfection into mouse primary hippocampal neurons, localizes at excitatory, but not inhibitory, postsynaptic sites.

Subcellular locations from

Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for ZC4H2 gene
Compartment Confidence
plasma membrane 5
nucleus 5
cytoskeleton 2
cytosol 1
extracellular 0

Subcellular locations from the

Human Protein Atlas (HPA)
  • Microtubules (2)
  • Vesicles (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for ZC4H2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA,IEA 23623388
GO:0005737 cytoplasm IEA,IDA 23623388
GO:0005886 plasma membrane IEA --
GO:0016020 membrane IEA --
GO:0030054 cell junction IEA --
genes like me logo Genes that share ontologies with ZC4H2: view

Pathways & Interactions for ZC4H2 Gene

PathCards logo

SuperPathways for ZC4H2 Gene

No Data Available

Gene Ontology (GO) - Biological Process for ZC4H2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007275 multicellular organism development IEA --
GO:0007399 nervous system development IDA 23623388
GO:0007528 neuromuscular junction development ISS --
GO:0021522 spinal cord motor neuron differentiation ISS --
GO:0030154 cell differentiation IEA --
genes like me logo Genes that share ontologies with ZC4H2: view

No data available for Pathways by source and SIGNOR curated interactions for ZC4H2 Gene

Drugs & Compounds for ZC4H2 Gene

No Compound Related Data Available

Transcripts for ZC4H2 Gene

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for ZC4H2 Gene

ExUns: 1 ^ 2a · 2b · 2c · 2d ^ 3 ^ 4a · 4b ^ 5a · 5b ^ 6 ^ 7a · 7b
SP1: - - - - -
SP2: - -
SP3: - -
SP4: -

Relevant External Links for ZC4H2 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for ZC4H2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for ZC4H2 Gene

Protein differential expression in normal tissues from HIPED for ZC4H2 Gene

This gene is overexpressed in Plasma (55.9) and Rectum (12.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for ZC4H2 Gene

Protein tissue co-expression partners for ZC4H2 Gene

NURSA nuclear receptor signaling pathways regulating expression of ZC4H2 Gene:


SOURCE GeneReport for Unigene cluster for ZC4H2 Gene:


mRNA Expression by UniProt/SwissProt for ZC4H2 Gene:

Tissue specificity: Expressed in fetal tissues, including in brain, intestine, lung, kidney and muscle (PubMed:23623388). Isoform 1 is expressed in numerous fetal brain regions. Isoform 3 is highly expressed in numerous fetal brain regions and spinal cord (PubMed:26056227).

Evidence on tissue expression from TISSUES for ZC4H2 Gene

  • Nervous system(4.8)
  • Intestine(4.2)
  • Pancreas(4.1)

Phenotype-based relationships between genes and organs from Gene ORGANizer for ZC4H2 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
  • digestive
  • integumentary
  • nervous
  • respiratory
  • skeletal muscle
  • skeleton
Head and neck:
  • brain
  • chin
  • cranial nerve
  • ear
  • eye
  • eyelid
  • face
  • forehead
  • head
  • jaw
  • lip
  • mandible
  • maxilla
  • mouth
  • neck
  • nose
  • outer ear
  • salivary gland
  • scalp
  • skull
  • tooth
  • chest wall
  • lung
  • rib
  • rib cage
  • sternum
  • pelvis
  • ankle
  • digit
  • elbow
  • femur
  • finger
  • foot
  • hand
  • hip
  • knee
  • lower limb
  • shoulder
  • thigh
  • toe
  • upper limb
  • wrist
  • hair
  • peripheral nerve
  • peripheral nervous system
  • skin
  • spinal column
  • spinal cord
  • vertebrae
genes like me logo Genes that share expression patterns with ZC4H2: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and mRNA differential expression in normal tissues for ZC4H2 Gene

Orthologs for ZC4H2 Gene

This gene was present in the common ancestor of animals.

Orthologs for ZC4H2 Gene

Organism Taxonomy Gene Similarity Type Details
(Monodelphis domestica)
Mammalia ZC4H2 33
  • 100 (a)
(Pan troglodytes)
Mammalia ZC4H2 33 32
  • 99.5 (n)
(Bos Taurus)
Mammalia ZC4H2 33 32
  • 94.05 (n)
(Canis familiaris)
Mammalia ZC4H2 33 32
  • 93.15 (n)
(Mus musculus)
Mammalia Zc4h2 17 33 32
  • 90.33 (n)
(Rattus norvegicus)
Mammalia Zc4h2 32
  • 90.03 (n)
(Ornithorhynchus anatinus)
Mammalia ZC4H2 33
  • 78 (a)
(Gallus gallus)
Aves ZC4H2 33 32
  • 82.14 (n)
(Anolis carolinensis)
Reptilia ZC4H2 33
  • 98 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia zc4h2 32
  • 81.99 (n)
Str.686 32
African clawed frog
(Xenopus laevis)
Amphibia Xl.22980 32
(Danio rerio)
Actinopterygii zc4h2 33 32
  • 77.83 (n)
wufb99f08 32
fruit fly
(Drosophila melanogaster)
Insecta CG13001 33 32
  • 63.17 (n)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP010728 32
  • 56.49 (n)
(Caenorhabditis elegans)
Secernentea vab-23 33
  • 28 (a)
ZK930.2 33
  • 24 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 33
  • 45 (a)
Cin.2141 32
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.2141 32
Species where no ortholog for ZC4H2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for ZC4H2 Gene

Gene Tree for ZC4H2 (if available)
Gene Tree for ZC4H2 (if available)
Evolutionary constrained regions (ECRs) for ZC4H2: view image

Paralogs for ZC4H2 Gene

No data available for Paralogs for ZC4H2 Gene

Variants for ZC4H2 Gene

Sequence variations from dbSNP and Humsavar for ZC4H2 Gene

SNP ID Clin Chr 0X pos Variation AA Info Type
rs1057520297 pathogenic, Wieacker Wolff syndrome, Wieacker-Wolf syndrome (WRWF) [MIM:314580] 64,921,845(-) A/T coding_sequence_variant, missense_variant, non_coding_transcript_variant
rs1057520298 likely-pathogenic, pathogenic, not provided, Wieacker Wolff syndrome 64,921,812(-) C/G/T intron_variant
rs1057520299 pathogenic, Wieacker Wolff syndrome 64,976,325(-) C/T coding_sequence_variant, intron_variant, missense_variant, non_coding_transcript_variant
rs1131691616 pathogenic-likely-pathogenic, pathogenic, not provided, Wieacker Wolff syndrome 64,921,843(-) G/A coding_sequence_variant, non_coding_transcript_variant, stop_gained
rs1260869746 pathogenic, Wieacker Wolff syndrome 64,919,176(-) G/A/T coding_sequence_variant, intron_variant, missense_variant, non_coding_transcript_variant, stop_gained

Structural Variations from Database of Genomic Variants (DGV) for ZC4H2 Gene

Variant ID Type Subtype PubMed ID
esv1584074 OTHER inversion 17803354
esv2663820 CNV deletion 23128226
esv2675440 CNV deletion 23128226
esv2758870 CNV gain 17122850
esv3558921 CNV deletion 23714750

Variation tolerance for ZC4H2 Gene

Residual Variation Intolerance Score: 44.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.22; 4.92% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for ZC4H2 Gene

Human Gene Mutation Database (HGMD)
SNPedia medical, phenotypic, and genealogical associations of SNPs for

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ZC4H2 Gene

Disorders for ZC4H2 Gene

MalaCards: The human disease database

(12) MalaCards diseases for ZC4H2 Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
wieacker-wolff syndrome
  • wrwf
intellectual disability-developmental delay-contractures syndrome
  • wieacker-wolff syndrome
miles-carpenter syndrome
  • miles-carpenter x-linked mental retardation syndrome
arthrogryposis multiplex congenita, neurogenic type
  • amcn
congenital contractures
  • congenital contracture
- elite association - COSMIC cancer census association via MalaCards
Search ZC4H2 in MalaCards View complete list of genes associated with diseases


  • Wieacker-Wolf syndrome (WRWF) [MIM:314580]: A severe X-linked recessive neurodevelopmental disorder affecting the central and peripheral nervous systems. It is characterized by onset of muscle weakness in utero (fetal akinesia). Affected boys are born with severe contractures, known as arthrogryposis, and have delayed motor development, facial and bulbar weakness, characteristic dysmorphic facial features, and skeletal abnormalities, such as hip dislocation, scoliosis, and pes equinovarus. Those that survive infancy show mental retardation. Carrier females may have mild features of the disorder. {ECO:0000269 PubMed:23623388, ECO:0000269 PubMed:26056227}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for ZC4H2

genes like me logo Genes that share disorders with ZC4H2: view

No data available for Genatlas for ZC4H2 Gene

Publications for ZC4H2 Gene

  1. ZC4H2, an XLID gene, is required for the generation of a specific subset of CNS interneurons. (PMID: 26056227) May M … Kim CH (Human molecular genetics 2015) 2 3 4 56
  2. ZC4H2 mutations are associated with arthrogryposis multiplex congenita and intellectual disability through impairment of central and peripheral synaptic plasticity. (PMID: 23623388) Hirata H … Kalscheuer VM (American journal of human genetics 2013) 2 3 4 56
  3. Large scale identification of human hepatocellular carcinoma-associated antigens by autoantibodies. (PMID: 12097419) Wang Y … Chen WF (Journal of immunology (Baltimore, Md. : 1950) 2002) 2 3 4 56
  4. Characterization of cDNA clones selected by the GeneMark analysis from size-fractionated cDNA libraries from human brain. (PMID: 10574461) Hirosawa M … Ohara O (DNA research : an international journal for rapid publication of reports on genes and genomes 1999) 2 3 4 56
  5. Genome-wide association study to identify single nucleotide polymorphisms (SNPs) associated with the development of erectile dysfunction in African-American men after radiotherapy for prostate cancer. (PMID: 20932654) Kerns SL … Rosenstein BS (International journal of radiation oncology, biology, physics 2010) 3 43 56

Products for ZC4H2 Gene

Sources for ZC4H2 Gene