CIC

Protein identityUniProt · HPA

UniProt accession

Q96RK0

Gene

CIC

Ensembl

ENSG00000079432

Chromosome

19

Canonical length

2517 aa

Protein class

Cancer-related genes, Disease related genes, Human disease related genes, Predicted intracellular proteins, Transcription factors

Subcellular location

Nucleoplasm,Vesicles

OverviewNCBI Gene

The protein encoded by this gene is an ortholog of the Drosophila melanogaster capicua gene, and is a member of the high mobility group (HMG)-box superfamily of transcriptional repressors. This protein contains a conserved HMG domain that is involved in DNA binding and nuclear localization, and a conserved C-terminus. Studies suggest that the N-terminal region of this protein interacts with Atxn1 (GeneID:6310), to form a transcription repressor complex, and in vitro studies suggest that polyglutamine-expansion of ATXN1 may alter the repressor activity of this complex. Mutations in this gene have been associated with olidogdendrogliomas (PMID:21817013). In addition, translocation events resulting in gene fusions of this gene with both DUX4 (GeneID:100288687) and FOXO4 (GeneID:4303) have been associated with round cell sarcomas. There are multiple pseudogenes of this gene found on chromosomes 1, 4, 6, 7, 16, 20, and the Y chromosome. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2015]

Canonical amino-acid sequenceUniProt

2517 residues, UniProt reviewed canonical sequence.

>Q96RK0|CIC
     1  MKPMKKACTG LSGPGSGSKS PPATRAKALR RRGAGEGDKP EEEDDEAQQP QPQSGPEEAE
    61  EGEEEEAERG PGAEGPPLEL HPGDPAPGPA EDPKGDGEAG RWEPSLSRKT ATFKSRAPKK
   121  KYVEEHGAGS SGVAGAPEER VRTPEEASGL GVPPRPPTST RSSSTDTASE HSADLEDEPA
   181  EACGPGPWPP GSTSGSYDLR QLRSQRVLAR RGDGLFLPAV VRQVRRSQDL GVQFPGDRAL
   241  TFYEGVPGAG VDVVLDATPP PGALVVGTAV CTCVEPGVAA YREGVVVEVA TKPAAYKVRL
   301  SPGPSSQPGL PGSLPQPPQP LHREPEEAVW VARSSLRLLR PPWEPETMLR KPPTGPEEEQ
   361  AEPGATLPPC PAALDPKQPE DAEVSKISFG GNLGTHCEEG EEKHPPALGT PALLPLPPPQ
   421  LLSPPPKSPA FVGPGRPGEQ PSPCQEGSQG GSRSSSVASL EKGTAPAARA RTPLTAAQQK
   481  YKKGDVVCTP SGIRKKFNGK QWRRLCSRDG CMKESQRRGY CSRHLSMRTK EMEGLADSGP
   541  GGAGRPAAVA AREGSTEFDW GDETSRDSEA SSVAARGDSR PRLVAPADLS RFEFDECEAA
   601  VMLVSLGSSR SGTPSFSPVS TQSPFSPAPS PSPSPLFGFR PANFSPINAS PVIQRTAVRS
   661  RHLSASTPKA GVLTPPDLGP HPPPPAPRER HSSGILPTFQ TNLTFTVPIS PGRRKTELLP
   721  HPGALGAPGA GGGGAAPDFP KSDSLDSGVD SVSHTPTPST PAGFRAVSPA VPFSRSRQPS
   781  PLLLLPPPAG LTSDPGPSVR RVPAVQRDSP VIVRNPDVPL PSKFPGEVGT AGEVRAGGPG
   841  RGCRETPVPP GVASGKPGLP PPLPAPVPIT VPPAAPTAVA QPMPAFGLAS SPFQPVAFHP
   901  SPAALLPVLV PSSYTSHPAP KKEVIMGRPG TVWTNVEPRS VAVFPWHSLV PFLAPSQPDP
   961  SVQPSEAQQP ASHPVASNQS KEPAESAAVA HERPPGGTGS ADPERPPGAT CPESPGPGPP
  1021  HPLGVVESGK GPPPTTEEEA SGPPGEPRLD SETESDHDDA FLSIMSPEIQ LPLPPGKRRT
  1081  QSLSALPKER DSSSEKDGRS PNKREKDHIR RPMNAFMIFS KRHRALVHQR HPNQDNRTVS
  1141  KILGEWWYAL GPKEKQKYHD LAFQVKEAHF KAHPDWKWCN KDRKKSSSEA KPTSLGLAGG
  1201  HKETRERSMS ETGTAAAPGV SSELLSVAAQ TLLSSDTKAP GSSSCGAERL HTVGGPGSAR
  1261  PRAFSHSGVH SLDGGEVDSQ ALQELTQMVS GPASYSGPKP STQYGAPGPF AAPGEGGALA
  1321  ATGRPPLLPT RASRSQRAAS EDMTSDEERM VICEEEGDDD VIADDGFGTT DIDLKCKERV
  1381  TDSESGDSSG EDPEGNKGFG RKVFSPVIRS SFTHCRPPLD PEPPGPPDPP VAFGKGYGSA
  1441  PSSSASSPAS SSASAATSFS LGSGTFKAQE SGQGSTAGPL RPPPPGAGGP ATPSKATRFL
  1501  PMDPATFRRK RPESVGGLEP PGPSVIAAPP SGGGNILQTL VLPPNKEEQE GGGARVPSAP
  1561  APSLAYGAPA APLSRPAATM VTNVVRPVSS TPVPIASKPF PTSGRAEASP NDTAGARTEM
  1621  GTGSRVPGGS PLGVSLVYSD KKSAAATSPA PHLVAGPLLG TVGKAPATVT NLLVGTPGYG
  1681  APAPPAVQFI AQGAPGGGTT AGSGAGAGSG PNGPVPLGIL QPGALGKAGG ITQVQYILPT
  1741  LPQQLQVAPA PAPAPGTKAA APSGPAPTTS IRFTLPPGTS TNGKVLAATA PTPGIPILQS
  1801  VPSAPPPKAQ SVSPVQAPPP GGSAQLLPGK VLVPLAAPSM SVRGGGAGQP LPLVSPPFSV
  1861  PVQNGAQPPS KIIQLTPVPV STPSGLVPPL SPATLPGPTS QPQKVLLPSS TRITYVQSAG
  1921  GHALPLGTSP ASSQAGTVTS YGPTSSVALG FTSLGPSGPA FVQPLLSAGQ APLLAPGQVG
  1981  VSPVPSPQLP PACAAPGGPV ITAFYSGSPA PTSSAPLAQP SQAPPSLVYT VATSTTPPAA
  2041  TILPKGPPAP ATATPAPTSP FPSATAGSMT YSLVAPKAQR PSPKAPQKVK AAIASIPVGS
  2101  FEAGASGRPG PAPRQPLEPG PVREPTAPES ELEGQPTPPA PPPLPETWTP TARSSPPLPP
  2161  PAEERTSAKG PETMASKFPS SSSDWRVPGQ GLENRGEPPT PPSPAPAPAV APGGSSESSS
  2221  GRAAGDTPER KEAAGTGKKV KVRPPPLKKT FDSVDNRVLS EVDFEERFAE LPEFRPEEVL
  2281  PSPTLQSLAT SPRAILGSYR KKRKNSTDLD SAPEDPTSPK RKMRRRSSCS SEPNTPKSAK
  2341  CEGDIFTFDR TGTEAEDVLG ELEYDKVPYS SLRRTLDQRR ALVMQLFQDH GFFPSAQATA
  2401  AFQARYADIF PSKVCLQLKI REVRQKIMQA ATPTEQPPGA EAPLPVPPPT GTAAAPAPTP
  2461  SPAGGPDPTS PSSDSGTAQA APPLPPPPES GPGQPGWEGA PQPSPPPPGP STAATGR

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CIC 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)

0.64

Highest tissue expression

105 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CIC.

Disease | AllUniProt

Conditions CIC is implicated in, by any mechanism.

• Intellectual developmental disorder, autosomal dominant 45 (MRD45) MIM:617600

Disease | GeneticClinVar

80 pathogenic / likely-pathogenic of 976 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Intellectual disability, autosomal dominant 45
• Inborn genetic diseases
• CIC-related disorder
• Anaplastic oligodendroglioma
• Marfanoid habitus and intellectual disability

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)

0.18

gnomAD pLI

1

gnomAD missense Z

0.73

DepMap mean gene effect

0.02

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

• brain development
• learning
• lung alveolus development
• memory
• negative regulation of DNA-templated transcription
• negative regulation of transcription by RNA polymerase II
• regulation of transcription by RNA polymerase II
• social behavior
• transcription by RNA polymerase II

Molecular functions

• chromatin binding
• DNA-binding transcription factor activity, RNA polymerase II-specific
• RNA polymerase II transcription regulatory region sequence-specific DNA binding

Cellular components

• chromatin
• nucleoplasm
• nucleus
• protein-containing complex

Protein domainsUniProt · Pfam · InterPro

• High mobility group box domain
• High mobility group box domain superfamily
• Cell Cycle and Developmental Transcription Regulators
• HMG (high mobility group) box
• Protein capicua homolog-like domain
• Protein capicua homolog-like, C-terminal tri-helical domain
• Protein capicua homolog-like, high mobility group box
• Protein capicua homolog-like domain
• Protein capicua homolog-like, C-terminal tri-helical domain

KeywordsUniProt

• Acetylation
• DNA-binding
• Intellectual disability
• Methylation
• Nucleus
• Phosphoprotein
• Repressor
• Transcription
• Transcription regulation

InteractionsUniProt · HPA

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

• ATXN1
• ATXN1L
• ATXN2L
• CPAP
• GOLGA2
• NFYC
• YWHAZ