ZC4H2 zinc finger C4H2-type containing [Homo sapiens (human)] - Gene

Summary

Official Symbol: ZC4H2provided by HGNC
Official Full Name: zinc finger C4H2-type containingprovided by HGNC
Primary source: HGNC:HGNC:24931
See related: Ensembl:ENSG00000126970 MIM:300897; AllianceGenome:HGNC:24931
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: MCS; WWS; WRWF; MRXS4; HCA127; WRWFFR; KIAA1166
Summary: 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]
Expression: Ubiquitous expression in brain (RPKM 4.1), endometrium (RPKM 3.2) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: Xq11.2

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	X	NC_000023.11 (64915807..65034741, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	X	NC_060947.1 (63341227..63460162, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	X	NC_000023.10 (64135687..64254621, complement)

Chromosome X - NC_000023.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Expanding allelic and phenotypic spectrum of ZC4H2-related disorder: A novel hypomorphic variant and high prevalence of tethered cord.
Title: Expanding allelic and phenotypic spectrum of ZC4H2-related disorder: A novel hypomorphic variant and high prevalence of tethered cord.
Sequential stabilization of RNF220 by RLIM and ZC4H2 during cerebellum development and Shh-group medulloblastoma progression.
Title: Sequential stabilization of RNF220 by RLIM and ZC4H2 during cerebellum development and Shh-group medulloblastoma progression.
A 7-year old female with arthrogryposis multiplex congenita, Duane retraction syndrome, and Marcus Gunn phenomenon due to a ZC4H2 gene mutation: a clinical presentation of the Wieacker-Wolff syndrome.
Title: A 7-year old female with arthrogryposis multiplex congenita, Duane retraction syndrome, and Marcus Gunn phenomenon due to a ZC4H2 gene mutation: a clinical presentation of the Wieacker-Wolff syndrome.
The Zinc-Finger Domain Containing Protein ZC4H2 Interacts with TRPV4, Enhancing Channel Activity and Turnover at the Plasma Membrane.
Title: The Zinc-Finger Domain Containing Protein ZC4H2 Interacts with TRPV4, Enhancing Channel Activity and Turnover at the Plasma Membrane.
Study reports on the genetic and clinical findings of 23 novel families and simplex cases of patients with arthrogryposis multiplex congenita (AMC). Deleterious inherited or de novo ZC4H2 variants were identified in males and females, including de novo partial ZC4H2 micro-deletions present in affected females only.
Title: Deleterious de novo variants of X-linked ZC4H2 in females cause a variable phenotype with neurogenic arthrogryposis multiplex congenita.
The present patient confirms that female carriers can also be severely affected. Systematic clinical investigations of both males and females are needed to define the variety in nature and severity of phenotypes related to ZC4H2 variants.
Title: ZC4H2 deletions can cause severe phenotype in female carriers.
ZC4H2, an XLID gene, is required for the generation of a specific subset of CNS interneurons
Title: ZC4H2, an XLID gene, is required for the generation of a specific subset of CNS interneurons.
ZC4H2 mutations are associated with arthrogryposis multiplex congenita and intellectual disability through impairment of central and peripheral synaptic plasticity.
Title: ZC4H2 mutations are associated with arthrogryposis multiplex congenita and intellectual disability through impairment of central and peripheral synaptic plasticity.

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Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Wieacker-Wolff syndrome MedGen: C0796200 OMIM: 314580 GeneReviews: Not available	not available
Wieacker-Wolff syndrome, female-restricted MedGen: C5393303 OMIM: 301041 GeneReviews: Not available	not available

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2020-04-22) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2020-04-22) ClinGen Genome Curation PagePubMed

EBI GWAS Catalog

Description
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. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:14125

A009J37 (e-PCR)
- UniSTS:28504

G32592 (e-PCR)
- UniSTS:117175

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in nervous system development	IDA Inferred from Direct Assay more info	PubMed
involved_in neuromuscular junction development	ISS Inferred from Sequence or Structural Similarity more info
involved_in noradrenergic neuron development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within positive regulation of DNA-binding transcription factor activity	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of neuron differentiation	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of neuron differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within protein monoubiquitination	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within regulation of transcription regulatory region DNA binding	IGI Inferred from Genetic Interaction more info	PubMed
involved_in spinal cord motor neuron differentiation	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in neuronal cell body	IEA Inferred from Electronic Annotation more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in postsynaptic membrane	IDA Inferred from Direct Assay more info	PubMed
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: zinc finger C4H2 domain-containing protein

Names: hepatocellular carcinoma-associated antigen 127; zinc finger, C4H2 domain containing

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_021200.2 RefSeqGene

Range

63295..123938

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001178032.3 → NP_001171503.1 zinc finger C4H2 domain-containing protein isoform 2

See identical proteins and their annotated locations for NP_001171503.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR, lacks a portion of the 5' coding region, and uses a downstream in-frame start codon, compared to variant 1. The encoded isoform (2) has a distinct N-terminus and is shorter than isoform 1. Both variants 2 and 4 encode the same isoform.

Source sequence(s)

AK001547, AK022807, BP376634

Consensus CDS

CCDS55431.1

UniProtKB/TrEMBL

A0A8V8TR70

Related

ENSP00000338650.2, ENST00000337990.2

Conserved Domains (1) summary

pfam10146
Location:1 → 198

zf-C4H2; Zinc finger-containing protein
NM_001178033.3 → NP_001171504.1 zinc finger C4H2 domain-containing protein isoform 3

See identical proteins and their annotated locations for NP_001171504.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an alternate exon in the 3' coding region that results in a frameshift, compared to variant 1. The resulting isoform (3) has a distinct C-terminus and is shorter than isoform 1.

Source sequence(s)

AK001547, AK293570

Consensus CDS

CCDS55432.1

UniProtKB/Swiss-Prot

Q9NQZ6

Related

ENSP00000399126.2, ENST00000447788.6

Conserved Domains (1) summary

pfam10146
Location:13 → 130

zf-C4H2; Zinc finger-containing protein
NM_001243804.2 → NP_001230733.1 zinc finger C4H2 domain-containing protein isoform 2

See identical proteins and their annotated locations for NP_001230733.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) differs in the 5' UTR, lacks a portion of the 5' coding region, and uses a downstream in-frame start codon, compared to variant 1. The encoded isoform (2) has a distinct N-terminus and is shorter than isoform 1. Both variants 2 and 4 encode the same isoform.

Source sequence(s)

AK001547, BP376634, CX782941

Consensus CDS

CCDS55431.1

UniProtKB/TrEMBL

A0A8V8TR70

Conserved Domains (1) summary

pfam10146
Location:1 → 198

zf-C4H2; Zinc finger-containing protein
NM_018684.4 → NP_061154.1 zinc finger C4H2 domain-containing protein isoform 1

See identical proteins and their annotated locations for NP_061154.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1).

Source sequence(s)

AK001547, BC004411

Consensus CDS

CCDS14380.1

UniProtKB/Swiss-Prot

B2RDC2, B3KVZ5, B4DED0, E7EM74, G3V1L3, Q53H73, Q5JTF9, Q9H9C3, Q9H9H7, Q9NQZ6, Q9ULQ4

Related

ENSP00000363972.3, ENST00000374839.8

Conserved Domains (1) summary

pfam10146
Location:13 → 221

zf-C4H2; Zinc finger-containing protein

RNA

NR_045044.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (5) uses an alternate splice site in the 5' region, compared to variant 1. This variant is represented as non-coding because the use of the supported start codon, as used by variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AK001547, AK022807, BI770655, DA037517