Seroatlas · Human Serome Atlas

C9orf72

Guanine nucleotide exchange factor C9orf72

Also known as: CI072_HUMAN, DENND9, DENNL72, MGC23980

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

Protein identityUniProt · HPA

UniProt accession
Q96LT7
Gene
C9orf72
Ensembl
ENSG00000147894
Chromosome
9
Canonical length
481 aa
Protein class
Disease related genes, Human disease related genes, Predicted intracellular proteins
Subcellular location
Vesicles,Midbody ring,Cytosol
Secretome location
Intracellular and membrane
Quaternary structure
Homodimer

OverviewNCBI Gene

The protein encoded by this gene plays an important role in the regulation of endosomal trafficking, and has been shown to interact with Rab proteins that are involved in autophagy and endocytic transport. Expansion of a GGGGCC repeat from 2-22 copies to 700-1600 copies in the intronic sequence between alternate 5' exons in transcripts from this gene is associated with 9p-linked ALS (amyotrophic lateral sclerosis) and FTD (frontotemporal dementia) (PMID: 21944778, 21944779). Studies suggest that hexanucleotide expansions could result in the selective stabilization of repeat-containing pre-mRNA, and the accumulation of insoluble dipeptide repeat protein aggregates that could be pathogenic in FTD-ALS patients (PMID: 23393093). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2016]

Canonical amino-acid sequenceUniProt

481 residues, UniProt reviewed canonical sequence.

>Q96LT7|C9orf72
     1  MSTLCPPPSP AVAKTEIALS GKSPLLAATF AYWDNILGPR VRHIWAPKTE QVLLSDGEIT
    61  FLANHTLNGE ILRNAESGAI DVKFFVLSEK GVIIVSLIFD GNWNGDRSTY GLSIILPQTE
   121  LSFYLPLHRV CVDRLTHIIR KGRIWMHKER QENVQKIILE GTERMEDQGQ SIIPMLTGEV
   181  IPVMELLSSM KSHSVPEEID IADTVLNDDD IGDSCHEGFL LNAISSHLQT CGCSVVVGSS
   241  AEKVNKIVRT LCLFLTPAER KCSRLCEAES SFKYESGLFV QGLLKDSTGS FVLPFRQVMY
   301  APYPTTHIDV DVNTVKQMPP CHEHIYNQRR YMRSELTAFW RATSEEDMAQ DTIIYTDESF
   361  TPDLNIFQDV LHRDTLVKAF LDQVFQLKPG LSLRSTFLAQ FLLVLHRKAL TLIKYIEDDT
   421  QKGKKPFKSL RNLKIDLDLT AEGDLNIIMA LAEKIKPGLH SFIFGRPFYT SVQERDVLMT
   481  F

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against C9orf72 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
Secreted
Secreted
Yes
Transmembrane segments
0
Mean surface accessibility (rSASA)
0.27
Highest tissue expression
33 nTPM

Expression across tissuesHPA

Tissue

  • cerebellum: 33 nTPM
  • retina: 29 nTPM
  • bone marrow: 24 nTPM
  • ovary: 23 nTPM
  • lung: 17 nTPM
  • testis: 17 nTPM

Single-cell type

  • neutrophils: 1,759 nCPM
  • monocytes: 528 nCPM
  • cdc: 334 nCPM
  • kupffer cells: 297 nCPM
  • müller glia: 270 nCPM
  • macrophages: 223 nCPM

Immune cell

  • intermediate monocyte: 45 nTPM
  • non-classical monocyte: 37 nTPM
  • neutrophil: 35 nTPM
  • classical monocyte: 32 nTPM
  • myeloid DC: 25 nTPM
  • basophil: 24 nTPM

Brain region

  • cerebellum: 42 nTPM
  • medulla oblongata: 29 nTPM
  • white matter: 27 nTPM
  • hypothalamus: 26 nTPM
  • spinal cord: 24 nTPM
  • choroid plexus: 24 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about C9orf72.

Disease | AllUniProt

Conditions C9orf72 is implicated in, by any mechanism.

  • Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 (FTDALS1) MIM:105550

Disease | GeneticClinVar

3 pathogenic / likely-pathogenic of 104 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Disease | ImmuneIEDB

Conditions an epitope on C9orf72 was assayed in.

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)
0.93
gnomAD pLI
0
gnomAD missense Z
0.24
DepMap mean gene effect
0.05
DepMap dependency class
selective

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

  • Guanine nucleotide exchange factor C9orf72
  • C9orf72-like protein family

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of C9orf72 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 C9orf72 as an antibody target. Whether an autoantibody or antibody against C9orf72 could matter depends on whether native C9orf72 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

C9orf72 is annotated as secreted, so native C9orf72 circulates and is directly accessible to antibodies. Secreted and cell-surface proteins are the autoantibody targets most likely to act like drugs, blocking or depleting the native protein.

Annotation status

The present source text does not explicitly label C9orf72 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/C9orf72. 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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