Seroatlas · Human Serome Atlas

ZCCHC8

Zinc finger CCHC domain-containing protein 8

Also known as: DKFZp434E2220, ZCHC8_HUMAN

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

Protein identityUniProt · HPA

UniProt accession
Q6NZY4
Gene
ZCCHC8
Ensembl
ENSG00000033030
Chromosome
12
Canonical length
707 aa
Protein class
Disease related genes, Human disease related genes, Predicted intracellular proteins
Subcellular location
Nucleoplasm

OverviewNCBI 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]

Canonical amino-acid sequenceUniProt

707 residues, UniProt reviewed canonical sequence.

>Q6NZY4|ZCCHC8
     1  MAAEVYFGDL ELFEPFDHPE ESIPKPVHTR FKDDDGDEED ENGVGDAELR ERLRQCEETI
    61  EQLRAENQEL KRKLNILTRP SGILVNDTKL DGPILQILFM NNAISKQYHQ EIEEFVSNLV
   121  KRFEEQQKND VEKTSFNLLP QPSSIVLEED HKVEESCAIK NNKEAFSVVG SVLYFTNFCL
   181  DKLGQPLLNE NPQLSEGWEI PKYHQVFSHI VSLEGQEIQV KAKRPKPHCF NCGSEEHQMK
   241  DCPMPRNAAR ISEKRKEYMD ACGEANNQNF QQRYHAEEVE ERFGRFKPGV ISEELQDALG
   301  VTDKSLPPFI YRMRQLGYPP GWLKEAELEN SGLALYDGKD GTDGETEVGE IQQNKSVTYD
   361  LSKLVNYPGF NISTPRGIPD EWRIFGSIPM QACQQKDVFA NYLTSNFQAP GVKSGNKRSS
   421  SHSSPGSPKK QKNESNSAGS PADMELDSDM EVPHGSQSSE SFQFQPPLPP DTPPLPRGTP
   481  PPVFTPPLPK GTPPLTPSDS PQTRTASGAV DEDALTLEEL EEQQRRIWAA LEQAESVNSD
   541  SDVPVDTPLT GNSVASSPCP NELDLPVPEG KTSEKQTLDE PEVPEIFTKK SEAGHASSPD
   601  SEVTSLCQKE KAELAPVNTE GALLDNGSVV PNCDISNGGS QKLFPADTSP STATKIHSPI
   661  PDMSKFATGI TPFEFENMAE STGMYLRIRS LLKNSPRNQQ KNKKASE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ZCCHC8 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)
0.57
Highest tissue expression
41 nTPM

Expression across tissuesHPA

Tissue

  • bone marrow: 41 nTPM
  • skeletal muscle: 12 nTPM
  • testis: 11 nTPM
  • tonsil: 11 nTPM
  • skin: 11 nTPM
  • spleen: 10 nTPM

Single-cell type

  • myonuclei: 132 nCPM
  • neutrophil progenitors: 121 nCPM
  • early spermatids: 101 nCPM
  • cone photoreceptor cells: 99 nCPM
  • erythrocyte progenitors: 92 nCPM
  • endometrial stromal cells: 78 nCPM

Immune cell

  • T-reg: 5.7 nTPM
  • basophil: 5.5 nTPM
  • naive CD4 T-cell: 4.6 nTPM
  • memory B-cell: 4.5 nTPM
  • NK-cell: 4.3 nTPM
  • non-classical monocyte: 4.3 nTPM

Brain region

  • cerebellum: 20 nTPM
  • choroid plexus: 16 nTPM
  • white matter: 15 nTPM
  • cerebral cortex: 14 nTPM
  • medulla oblongata: 13 nTPM
  • pons: 13 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ZCCHC8.

Disease | AllUniProt

Conditions ZCCHC8 is implicated in, by any mechanism.

  • Pulmonary fibrosis, and/or bone marrow failure syndrome, telomere-related, 5 (PFBMFT5) MIM:618674

Disease | GeneticClinVar

5 pathogenic / likely-pathogenic of 505 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)
0.32
gnomAD pLI
0.97
gnomAD missense Z
2.03

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

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of ZCCHC8 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 ZCCHC8 as an antibody target. Whether an autoantibody or antibody against ZCCHC8 could matter depends on whether native ZCCHC8 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

ZCCHC8 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label ZCCHC8 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/ZCCHC8. 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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