CIC
Chr 19ADcapicua transcriptional repressor
Also known as: MRD45
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]
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
This gene — mechanism propensity
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
References
ClinVar Variant Classifications
979 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 29 | 1 | 1 | 0 | 31 |
Likely Pathogenic | 40 | 10 | 0 | 1 | 51 |
VUS | 19 | 472 | 11 | 11 | 513 |
Likely Benign | 1 | 105 | 17 | 157 | 280 |
Benign | 0 | 6 | 2 | 9 | 17 |
Conflicting | — | 28 | |||
| Total | 89 | 594 | 31 | 178 | 920 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →9 pathogenic / likely-pathogenic (of 11) ClinVar copy-number / structural variants overlap CIC — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →
Protein Context — Lollipop Plot
CIC · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
BTX-A51 in Patients With Liposarcoma or CIC-rearranged Sarcoma
ACTIVE NOT RECRUITINGImpaired Type I IFN Immunity Due to Autoantibodies or a Genetic Defect: a Prospective National Cohort
RECRUITINGAdditional Support Program Via Text Messaging and Telephone-Based Counseling for Breast Cancer Patients Receiving Hormonal Therapy
ACTIVE NOT RECRUITINGLung-MAP: A Master Screening Protocol for Previously-Treated Non-Small Cell Lung Cancer
RECRUITINGAdding the Immunotherapy Drug Cemiplimab to Usual Treatment for People With Advanced Non-Small Cell Lung Cancer Who Had Previous Treatment With Platinum Chemotherapy and Immunotherapy (An Expanded Lung-MAP Treatment Trial)
RECRUITINGGENES AND AUTISM - Induced Pluripotent Stem Cells
NOT YET RECRUITINGDabrafenib and Trametinib Followed by Ipilimumab and Nivolumab or Ipilimumab and Nivolumab Followed by Dabrafenib and Trametinib in Treating Patients With Stage III-IV BRAFV600 Melanoma
ACTIVE NOT RECRUITINGCharacterization and Contribution of Genome-wide DNA Methylation (DNA Methylation Episignatures) in Rare Diseases With Prenatal Onset
RECRUITINGRisk of Posterior Staphyloma in Highly Myopic Europeans : From Epidemiology to Anatomy.
RECRUITINGSafety and Efficacy Study of Transplantation of Autologous CD34+ Cells Transduced With the G2ARTE Lentiviral Vector Expressing the DCLRE1C cDNA in Artemis (DCLRE1C) Deficient Severe Combined Immunodeficiency Patients (ARTEGENE)
RECRUITINGOnline Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight
RECRUITINGEfficacy and Safety of Olaparib (MK-7339) in Participants With Previously Treated, Homologous Recombination Repair Mutation (HRRm) or Homologous Recombination Deficiency (HRD) Positive Advanced Cancer (MK-7339-002 / LYNK-002)
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools