CIC

Chr 19

capicua 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]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtIntellectual developmental disorder, autosomal dominant 45

Clinical highlights

Gene-disease validity (ClinGen)
complex neurodevelopmental disorder · ADDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
12
Active trials
764
Pubs (1 yr)
P/LP submissions
P/LP missense
0.18
LOEUF· LoF intol.
LOF
Mechanism· G2P
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint?
0.18LOEUF
pLI 1.000
Z-score 6.02
OE 0.08 (0.040.18)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
0.73Z-score
OE missense 0.93 (0.880.99)
904 obs / 967.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.08 (0.040.18)
00.351.4
Missense OE?0.93 (0.880.99)
00.61.4
Synonymous OE?1.28
01.21.6
LoF obs/exp: 4 / 49.9Missense obs/exp: 904 / 967.5Syn Z: -4.48

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CIC · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Sickle Cell Disease

Efficacy Safety Study of Gene Therapy for Sickle Cell DiseaseSCD Using Autologous CD34+ Cells Transduced ex Vivo, Carrying a Corrected Globin Gene and a Silencing RNA.

RECRUITING
NCT07432867Phase PHASE1, PHASE2Assistance Publique - Hôpitaux de ParisStarted 2026-02-25
DREAM01 drug productanti-inflammatory therapy
Stage II Colorectal Cancer AJCC v8Stage III Colorectal Cancer AJCC v8

Duloxetine to Prevent Oxaliplatin-Induced Peripheral Neuropathy in Patients With Stage II-III Colorectal Cancer

ACTIVE NOT RECRUITING
NCT04137107Phase PHASE2, PHASE3Alliance for Clinical Trials in OncologyStarted 2020-06-17
OxaliplatinDuloxetine HydrochlorideDuloxetine
Hidradenitis Suppurativa (HS)Fecal Microbiota Transplantation (FMT)

FEcal tranSplantation in HidradeniTIs suppuratiVA : a piLot Study

NOT YET RECRUITING
NCT07668713Phase PHASE1University Hospital, Clermont-FerrandStarted 2026-06-01
Fecal microbiota transplantation (FMT)
Osteoporosis, Postmenopausal

Vascular Function, Sarcopenia and Pain in Postmenopausal Osteoporosis

RECRUITING
NCT05228262Phase NAUniversity Hospital, Clermont-FerrandStarted 2022-02-15
Cohort follow-up
Breast Ductal Carcinoma In SituInvasive Breast CarcinomaStage II Breast Cancer AJCC v6 and v7

Breast Cancer WEight Loss Study (BWEL Study)

ACTIVE NOT RECRUITING
NCT02750826Phase PHASE3Alliance for Clinical Trials in OncologyStarted 2016-09-16
Health Education ProgramWeight Loss Intervention
High Myopia

Risk of Posterior Staphyloma in Highly Myopic Europeans : From Epidemiology to Anatomy.

RECRUITING
NCT06949579Phase NAAssistance Publique - Hôpitaux de ParisStarted 2026-02-12
blood sampling for DNA
Monogenic DiseasesGenetic Diseases, Inborn

Health Economic Evaluation of Non-Invasive Prenatal Exclusion Diagnosis

RECRUITING
NCT07469657Assistance Publique - Hôpitaux de ParisStarted 2026-03-26
NIPD by NGS
Advanced Solid Neoplasms

Efficacy 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 RECRUITING
NCT03742895Phase PHASE2Merck Sharp & Dohme LLCStarted 2018-12-12
Olaparib
Breast CancerCognitive Impairments

Cognitive Training for Cancer Related Cognitive Impairment in Breast Cancer Survivors

ACTIVE NOT RECRUITING
NCT05896189Phase NANRG OncologyStarted 2024-02-29
Arm 1: Computerized Cognitive Training-Global Stimulation GamesArm 2: Computerized Cognitive Training-Neuroplasticity Games
Birdshot ChorioretinopathyPosterior Uveitis

Birdshot Chorioretinopathy : Prospective Follow-up and Immunogenetic Studies(CO-BIRD)

RECRUITING
NCT05153057Assistance Publique - Hôpitaux de ParisStarted 2004-11-02
Observational study
Spinal Muscular Atrophy

Quantification of Motor Function in Infants With Spinal Muscular Atrophy Treated With Innovative Therapies

ACTIVE NOT RECRUITING
NCT04833348Phase NAAssistance Publique - Hôpitaux de ParisStarted 2021-03-20
Motor function measurement using inertial sensors
AdrenoleukodystrophyAdrenomyeloneuropathyMetachromatic Leukodystrophy

Modeling Macrophages Activation Pattern in X-linked Adrenoleukodystrophy, Metachromatic Leukodystrophy and Adult Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia

RECRUITING
NCT04925349Assistance Publique - Hôpitaux de ParisStarted 2021-08-30
Blood sample collection