This gene encodes a scaffold protein which serves as an assessory factor to the nuclear RNA exosome complex. The encoded protein forms a trimeric human nuclear exosome targeting (NEXT) complex, together with hMTR4 and the RNA-binding factor RBM7 which promotes the exosomal degradation of non-coding promoter-upstream transcripts, enhancer RNAs and 3'-extended products of histone... See more...

Aliases for ZCCHC8 Gene

Aliases for ZCCHC8 Gene

  • Zinc Finger CCHC-Type Containing 8 2 3 5
  • Zinc Finger CCHC Domain-Containing Protein 8 3 4
  • TRAMP-Like Complex RNA-Binding Factor ZCCHC8 3 4
  • Zinc Finger, CCHC Domain Containing 8 3
  • PFBMFT5 3

External Ids for ZCCHC8 Gene

Previous GeneCards Identifiers for ZCCHC8 Gene

  • GC12M121395
  • GC12M121482
  • GC12M122958
  • GC12M119918

Summaries for ZCCHC8 Gene

Entrez Gene Summary for ZCCHC8 Gene

  • This gene encodes a scaffold protein which serves as an assessory factor to the nuclear RNA exosome complex. The encoded protein forms a trimeric human nuclear exosome targeting (NEXT) complex, together with hMTR4 and the RNA-binding factor RBM7 which promotes the exosomal degradation of non-coding promoter-upstream transcripts, enhancer RNAs and 3'-extended products of histone- and small nuclear RNA transcription. This complex is also thought to recruit the exosome to degrade intronic RNAs via its interaction with both the exosome and the spliceosome. It contains both an N-terminal zinc-knuckle domain and a C-terminal proline-rich domain. [provided by RefSeq, Apr 2017]

GeneCards Summary for ZCCHC8 Gene

ZCCHC8 (Zinc Finger CCHC-Type Containing 8) is a Protein Coding gene. Diseases associated with ZCCHC8 include Pulmonary Fibrosis And/Or Bone Marrow Failure, Telomere-Related, 5 and Pulmonary Fibrosis.

UniProtKB/Swiss-Prot Summary for ZCCHC8 Gene

  • Scaffolding subunit of the trimeric nuclear exosome targeting (NEXT) complex. NEXT functions as an RNA exosome cofactor that directs a subset of non-coding short-lived RNAs for exosomal degradation. NEXT is involved in surveillance and turnover of aberrant transcripts and non-coding RNAs (PubMed:27871484). May be involved in pre-mRNA splicing (Probable).

Gene Wiki entry for ZCCHC8 Gene

Additional gene information for ZCCHC8 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for ZCCHC8 Gene

Genomics for ZCCHC8 Gene

GeneHancer (GH) Regulatory Elements for ZCCHC8 Gene

Promoters and enhancers for ZCCHC8 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around ZCCHC8 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for ZCCHC8

Top Transcription factor binding sites by QIAGEN in the ZCCHC8 gene promoter:
  • E4BP4
  • Egr-2
  • Evi-1
  • HEN1
  • Lmo2
  • PPAR-gamma1
  • PPAR-gamma2
  • RSRFC4

Genomic Locations for ZCCHC8 Gene

Genomic Locations for ZCCHC8 Gene
chr12:122,471,599-122,501,073
(GRCh38/hg38)
Size:
29,475 bases
Orientation:
Minus strand
chr12:122,956,146-122,985,543
(GRCh37/hg19)
Size:
29,398 bases
Orientation:
Minus strand

Genomic View for ZCCHC8 Gene

Genes around ZCCHC8 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ZCCHC8 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ZCCHC8 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ZCCHC8 Gene

Proteins for ZCCHC8 Gene

  • Protein details for ZCCHC8 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q6NZY4-ZCHC8_HUMAN
    Recommended name:
    Zinc finger CCHC domain-containing protein 8
    Protein Accession:
    Q6NZY4
    Secondary Accessions:
    • Q7L2P6
    • Q8N2K5
    • Q96SK7
    • Q9NSS2
    • Q9NSS3

    Protein attributes for ZCCHC8 Gene

    Size:
    707 amino acids
    Molecular mass:
    78577 Da
    Quaternary structure:
    • Component of a nuclear TRAMP-like complex, an ATP-dependent exosome regulatory complex consisting of a helicase (MTREX), an oligadenylate polymerase (TENT4B or TENT4A), and a substrate specific RNA-binding factor (ZCCHC7 or ZCCHC8). Several TRAMP-like complexes exist with specific compositions and are associated with nuclear, or nucleolar RNA exosomes. Identified in the spliceosome C complex. Component of the nuclear exosome targeting (NEXT) complex composed of MTREX, ZCCHC8, and RBM7 that directs a subset of non-coding short-lived RNAs for exosomal degradation (PubMed:27905398, PubMed:27871484). Interacts with proteins involved in RNA processing and degradation such as MTREX and RBM7; interaction with MTREX enhances MTREX RNA helicase activity and bridges between RBM7 and MTREX (PubMed:16263084, PubMed:27905398, PubMed:27871484).

    Three dimensional structures from OCA and Proteopedia for ZCCHC8 Gene

    Alternative splice isoforms for ZCCHC8 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for ZCCHC8 Gene

Post-translational modifications for ZCCHC8 Gene

  • Phosphorylation at Thr-492 by GSK3 is triggered in cells entering mitosis; this phosphorylation is greatly enhanced by nocodazole treatment, but reduced by lithium.
  • Ubiquitination at Lys363
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for ZCCHC8 Gene

Domains & Families for ZCCHC8 Gene

Gene Families for ZCCHC8 Gene

Protein Domains for ZCCHC8 Gene

Blocks:
  • C2HC-type zinc-finger signature
  • PSP, proline-rich
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for ZCCHC8 Gene

GenScript: Design optimal peptide antigens:
  • Zinc finger CCHC domain-containing protein 8 (ZCHC8_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q6NZY4

UniProtKB/Swiss-Prot:

ZCHC8_HUMAN :
  • The C-terminal part (659-707) contributes to MTREX RNA helicase activity, in part, by enhancing its RNA-dependent ATPase activity.
  • Belongs to the ZCCHC8 family.
Domain:
  • The C-terminal part (659-707) contributes to MTREX RNA helicase activity, in part, by enhancing its RNA-dependent ATPase activity.
Family:
  • Belongs to the ZCCHC8 family.
genes like me logo Genes that share domains with ZCCHC8: view

Function for ZCCHC8 Gene

Molecular function for ZCCHC8 Gene

UniProtKB/Swiss-Prot Function:
Scaffolding subunit of the trimeric nuclear exosome targeting (NEXT) complex. NEXT functions as an RNA exosome cofactor that directs a subset of non-coding short-lived RNAs for exosomal degradation. NEXT is involved in surveillance and turnover of aberrant transcripts and non-coding RNAs (PubMed:27871484). May be involved in pre-mRNA splicing (Probable).
UniProtKB/Swiss-Prot Induction:
Slight accumulation in cells entering S phase of the cell cycle.

Phenotypes From GWAS Catalog for ZCCHC8 Gene

Gene Ontology (GO) - Molecular Function for ZCCHC8 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003676 nucleic acid binding IEA --
GO:0003723 RNA binding HDA 22658674
GO:0005515 protein binding IPI 16263084
GO:0008270 zinc ion binding IEA --
GO:0046872 metal ion binding IEA --
genes like me logo Genes that share ontologies with ZCCHC8: view

Phenotypes for ZCCHC8 Gene

genes like me logo Genes that share phenotypes with ZCCHC8: view

Animal Model Products

CRISPR Products

miRNA for ZCCHC8 Gene

miRTarBase miRNAs that target ZCCHC8

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for ZCCHC8 Gene

Localization for ZCCHC8 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ZCCHC8 Gene

Nucleus, nucleoplasm. Nucleus. Note=Excluded from nucleolus. {ECO:0000269 PubMed:21855801}.

Subcellular locations from

COMPARTMENTS
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 ZCCHC8 gene
Compartment Confidence
nucleus 5
extracellular 2
cytosol 2
cytoskeleton 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for ZCCHC8 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA,IEA 21855801
GO:0005654 nucleoplasm IDA,IEA 16263084
GO:0005681 spliceosomal complex IEA --
GO:0005730 NOT nucleolus IDA 21855801
GO:0016604 nuclear body IDA --
genes like me logo Genes that share ontologies with ZCCHC8: view

Pathways & Interactions for ZCCHC8 Gene

PathCards logo

SuperPathways for ZCCHC8 Gene

No Data Available

Gene Ontology (GO) - Biological Process for ZCCHC8 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000398 mRNA splicing, via spliceosome IC 11991638
GO:0006397 mRNA processing IEA --
GO:0008380 RNA splicing IEA --
GO:0016076 snRNA catabolic process ISS --
genes like me logo Genes that share ontologies with ZCCHC8: view

No data available for Pathways by source and SIGNOR curated interactions for ZCCHC8 Gene

Drugs & Compounds for ZCCHC8 Gene

No Compound Related Data Available

Transcripts for ZCCHC8 Gene

mRNA/cDNA for ZCCHC8 Gene

5 REFSEQ mRNAs :
12 NCBI additional mRNA sequence :
11 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for ZCCHC8 Gene

ExUns: 1a · 1b · 1c · 1d ^ 2a · 2b ^ 3 ^ 4a · 4b ^ 5 ^ 6a · 6b ^ 7 ^ 8 ^ 9a · 9b ^ 10a · 10b ^ 11a · 11b · 11c ^ 12 ^ 13 ^ 14a · 14b ^ 15 ^
SP1: - - - - - -
SP2: - - - - - - - -
SP3: - - - - - -
SP4: - - - - - - - - - -
SP5: - - -
SP6: - -
SP7:
SP8: - -
SP9:

ExUns: 16a · 16b
SP1:
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:

Relevant External Links for ZCCHC8 Gene

GeneLoc Exon Structure for
ZCCHC8

Expression for ZCCHC8 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for ZCCHC8 Gene

Protein differential expression in normal tissues from HIPED for ZCCHC8 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (11.8) and Lymph node (8.8).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for ZCCHC8 Gene



Protein tissue co-expression partners for ZCCHC8 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for ZCCHC8

SOURCE GeneReport for Unigene cluster for ZCCHC8 Gene:

Hs.37706

Evidence on tissue expression from TISSUES for ZCCHC8 Gene

  • Nervous system(4.4)
  • Intestine(4.3)
  • Liver(4.2)
genes like me logo Genes that share expression patterns with ZCCHC8: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for ZCCHC8 Gene

Orthologs for ZCCHC8 Gene

This gene was present in the common ancestor of animals.

Orthologs for ZCCHC8 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia ZCCHC8 31 30
  • 98.83 (n)
OneToOne
dog
(Canis familiaris)
Mammalia ZCCHC8 31 30
  • 88.18 (n)
OneToOne
cow
(Bos Taurus)
Mammalia ZCCHC8 31 30
  • 87.23 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Zcchc8 17 31 30
  • 82.46 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia ZCCHC8 31
  • 74 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia ZCCHC8 31
  • 71 (a)
OneToOne
chicken
(Gallus gallus)
Aves ZCCHC8 31 30
  • 70.5 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia ZCCHC8 31
  • 58 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia zcchc8 30
  • 64.58 (n)
Str.16750 30
African clawed frog
(Xenopus laevis)
Amphibia Xl.2647 30
zebrafish
(Danio rerio)
Actinopterygii zcchc8 31 30
  • 54.73 (n)
OneToOne
Dr.17330 30
fruit fly
(Drosophila melanogaster)
Insecta CG4622 31
  • 29 (a)
OneToOne
worm
(Caenorhabditis elegans)
Secernentea Y34D9A.7 31
  • 25 (a)
OneToMany
ZK632.11 31
  • 23 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 33 (a)
OneToOne
Species where no ortholog for ZCCHC8 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • 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)
  • rat (Rattus norvegicus)
  • 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 ZCCHC8 Gene

ENSEMBL:
Gene Tree for ZCCHC8 (if available)
TreeFam:
Gene Tree for ZCCHC8 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for ZCCHC8: view image

Paralogs for ZCCHC8 Gene

No data available for Paralogs for ZCCHC8 Gene

Variants for ZCCHC8 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for ZCCHC8 Gene

SNP ID Clinical significance and condition Chr 12 pos Variation AA Info Type
694674 Pathogenic: PULMONARY FIBROSIS AND/OR BONE MARROW FAILURE, TELOMERE-RELATED, 5 122,483,508(-) G/A MISSENSE_VARIANT,INTRON_VARIANT
722877 Benign: not provided 122,482,625(-) A/G INTRON_VARIANT
734558 Likely Benign: not provided 122,474,071(-) A/G MISSENSE_VARIANT
761516 Likely Benign: not provided 122,473,773(-) C/T SYNONYMOUS_VARIANT
764572 Likely Benign: not provided 122,498,829(-) C/T SYNONYMOUS_VARIANT,FIVE_PRIME_UTR_VARIANT,INTRON_VARIANT

Additional dbSNP identifiers (rs#s) for ZCCHC8 Gene

Structural Variations from Database of Genomic Variants (DGV) for ZCCHC8 Gene

Variant ID Type Subtype PubMed ID
esv3630977 CNV gain 21293372
nsv1113530 CNV deletion 24896259
nsv1134272 CNV deletion 24896259

Variation tolerance for ZCCHC8 Gene

Gene Damage Index Score: 2.50; 43.81% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for ZCCHC8 Gene

Human Gene Mutation Database (HGMD)
ZCCHC8
SNPedia medical, phenotypic, and genealogical associations of SNPs for
ZCCHC8

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ZCCHC8 Gene

Disorders for ZCCHC8 Gene

MalaCards: The human disease database

(2) MalaCards diseases for ZCCHC8 Gene - From: OMIM, ClinVar, DISEASES, and GeneCards

- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for ZCCHC8

genes like me logo Genes that share disorders with ZCCHC8: view

No data available for UniProtKB/Swiss-Prot and Genatlas for ZCCHC8 Gene

Publications for ZCCHC8 Gene

  1. Zcchc8 is a glycogen synthase kinase-3 substrate that interacts with RNA-binding proteins. (PMID: 16263084) Gustafson MP … Clurman BE (Biochemical and biophysical research communications 2005) 2 3 4 23 54
  2. Interaction profiling identifies the human nuclear exosome targeting complex. (PMID: 21855801) Lubas M … Jensen TH (Molecular cell 2011) 2 3 4 54
  3. Structural basis for MTR4-ZCCHC8 interactions that stimulate the MTR4 helicase in the nuclear exosome-targeting complex. (PMID: 29844170) Puno MR … Lima CD (Proceedings of the National Academy of Sciences of the United States of America 2018) 3 4 54
  4. Structure of the RBM7-ZCCHC8 core of the NEXT complex reveals connections to splicing factors. (PMID: 27905398) Falk S … Conti E (Nature communications 2016) 3 4 54
  5. Identification of a Nuclear Exosome Decay Pathway for Processed Transcripts. (PMID: 27871484) Meola N … Jensen TH (Molecular cell 2016) 3 4 54

Products for ZCCHC8 Gene

Sources for ZCCHC8 Gene