ZIC3

Protein identityUniProt · HPA

UniProt accession

O60481

Gene

ZIC3

Ensembl

ENSG00000156925

Chromosome

X

Canonical length

467 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 ZIC family of C2H2-type zinc finger proteins. This nuclear protein probably functions as a transcription factor in early stages of left-right body axis formation. Mutations in this gene cause X-linked visceral heterotaxy, which includes congenital heart disease and left-right axis defects in organs. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

467 residues, UniProt reviewed canonical sequence.

>O60481|ZIC3
     1  MTMLLDGGPQ FPGLGVGSFG APRHHEMPNR EPAGMGLNPF GDSTHAAAAA AAAAAFKLSP
    61  AAAHDLSSGQ SSAFTPQGSG YANALGHHHH HHHHHHHTSQ VPSYGGAASA AFNSTREFLF
   121  RQRSSGLSEA ASGGGQHGLF AGSASSLHAP AGIPEPPSYL LFPGLHEQGA GHPSPTGHVD
   181  NNQVHLGLRG ELFGRADPYR PVASPRTDPY AAGAQFPNYS PMNMNMGVNV AAHHGPGAFF
   241  RYMRQPIKQE LSCKWIDEAQ LSRPKKSCDR TFSTMHELVT HVTMEHVGGP EQNNHVCYWE
   301  ECPREGKSFK AKYKLVNHIR VHTGEKPFPC PFPGCGKIFA RSENLKIHKR THTGEKPFKC
   361  EFEGCDRRFA NSSDRKKHMH VHTSDKPYIC KVCDKSYTHP SSLRKHMKVH ESQGSDSSPA
   421  ASSGYESSTP PAIASANSKD TTKTPSAVQT STSHNPGLPP NFNEWYV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ZIC3 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)

0.62

Highest tissue expression

18 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ZIC3.

Disease | AllUniProt

Conditions ZIC3 is implicated in, by any mechanism.

• Heterotaxy, visceral, 1, X-linked (HTX1) MIM:306955
• VACTERL association X-linked with or without hydrocephalus (VACTERLX) MIM:314390
• Congenital heart defects, multiple types, 1, X-linked (CHTD1) MIM:306955

Disease | GeneticClinVar

41 pathogenic / likely-pathogenic of 195 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Heterotaxy, visceral, 1, X-linked
• VACTERL association, X-linked, with or without hydrocephalus
• ZIC3-related disorder
• Congenital heart defects, multiple types, 1, X-linked
• Inborn genetic diseases

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)

0.36

gnomAD pLI

0.92

gnomAD missense Z

2.52

DepMap mean gene effect

0.05

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

• atrial cardiac muscle tissue development
• axial mesoderm development
• central nervous system development
• cranial skeletal system development
• determination of digestive tract left/right asymmetry
• determination of left/right asymmetry in nervous system
• determination of left/right symmetry
• determination of liver left/right asymmetry
• determination of pancreatic left/right asymmetry
• embryonic pattern specification
• face development
• germ-line stem cell population maintenance
• heart looping
• hippocampus development
• left/right axis specification
• limb morphogenesis
• lung development
• mRNA transcription by RNA polymerase II
• neural plate development
• neuron differentiation
• olfactory bulb development
• outer ear morphogenesis
• paraxial mesoderm development
• positive regulation of DNA-templated transcription
• positive regulation of transcription by RNA polymerase II
• primitive streak formation
• skeletal system development
• smoothened signaling pathway
• stem cell differentiation
• central nervous system segmentation

Molecular functions

• DNA-binding transcription activator activity, RNA polymerase II-specific
• DNA-binding transcription factor activity
• DNA-binding transcription factor activity, RNA polymerase II-specific
• RNA polymerase II cis-regulatory region sequence-specific DNA binding
• sequence-specific DNA binding
• sequence-specific double-stranded DNA binding
• transcription coactivator activity
• zinc ion binding

Cellular components

• cytoplasm
• nucleoplasm
• nucleus

Protein domainsUniProt · Pfam · InterPro

• Zinc finger C2H2-type
• Zinc finger C2H2 superfamily
• ZIC protein, zinc finger domain
• C2H2-type zinc-finger protein GLI-like
• ZIC1-5/GLI1-3like, C2H2 zinc finger
• Zinc finger, C2H2 type
• Zic proteins zinc finger domain
• C2H2 zinc finger

KeywordsUniProt

• Activator
• Cytoplasm
• Developmental protein
• Differentiation
• DNA-binding
• Heterotaxy
• Isopeptide bond
• Metal-binding
• Neurogenesis
• Nucleus
• Repeat
• Transcription
• Transcription regulation
• Triplet repeat expansion
• Ubl conjugation
• Zinc
• Zinc-finger

InteractionsUniProt · HPA

Protein binding partners of ZIC3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• KPNA1
• KPNA6
• GLI3