CIC

Chr 19AD

capicua transcriptional repressor

Also known as: MRD45

This protein functions as a transcriptional repressor that regulates central nervous system development, working in concert with ATXN1 and ATXN1L in brain development. Mutations cause autosomal dominant intellectual developmental disorder. The gene is highly constrained against loss-of-function variants (pLI 1.0, LOEUF 0.18), indicating that heterozygous loss is not well-tolerated in the general population.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.181 OMIM phenotype
Clinical SummaryCIC
🧬
Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
💊
Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available

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 OE0.08 (0.040.18)
00.351.4
Missense OE0.93 (0.880.99)
00.61.4
Synonymous OE1.28
01.21.6
LoF obs/exp: 4 / 49.9Missense obs/exp: 904 / 967.5Syn Z: -4.48
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongCIC-related neurodevelopmental disorderLOFAD
DN
0.2299th %ile
GOF
0.2597th %ile
LOF
0.84top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · LOEUF 0.18

Literature Evidence

LOFHere we review four examples from our research group where studying the consequences of altered gene dosage in a mouse led to the discovery of previously unrecognized human syndromes: MECP2 duplication syndrome, SHANK3 duplication syndrome, CIC haploinsufficiency syndrome, and PUM1-related disordersPMID:30030131

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Breast CancerDepression

E-Mindfulness Approaches for Living After Breast Cancer

RECRUITING
NCT06748222Phase PHASE3NRG OncologyStarted 2025-06-27
Mindfulness (MAPs) Live OnlineMindfulness (MAPs) Digital AppMeditation Only Control Group
Recurrent Lung Non-Small Cell CarcinomaStage IV Lung Cancer AJCC v8

Adding 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)

RECRUITING
NCT06616584Phase PHASE2, PHASE3SWOG Cancer Research NetworkStarted 2025-05-22
Biospecimen CollectionCemiplimabComputed Tomography
Humoral Primary Immunodeficiencies (PIDs)Secondary Form of Humoral ImmunodeficienciesCombined Immunodeficiency (CID)

Study of Populations at Risk of Developing Chronic Hepatitis Linked to Chronic Enteric Virus Infection in Patients With Primary Immunodeficiency and Secondary Humoral Deficiency

RECRUITING
NCT06659588Assistance Publique - Hôpitaux de ParisStarted 2024-10-10
Plasma, urine and stool collection
Breast AdenocarcinomaHormone Receptor PositiveStage IA Breast Cancer AJCC v7

Hormone Therapy With or Without Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Negative Breast Cancer (The TAILORx Trial)

ACTIVE NOT RECRUITING
NCT00310180Phase PHASE3National Cancer Institute (NCI)Started 2006-04-07
AnastrozoleExemestaneLaboratory Biomarker Analysis
Retinitis Pigmentosa

Promising ROd-cone DYstrophy Gene therapY

RECRUITING
NCT05748873Phase PHASE1, PHASE2SparingVisionStarted 2023-04-12
SPVN06
Autism DisorderASD

GENES AND AUTISM - IPSC

NOT YET RECRUITING
NCT07311213Phase NAInstitut National de la Santé Et de la Recherche Médicale, FranceStarted 2026-02-01
Blood Sample : isolation of peripheral blood mononuclear cells (PBMCs)
Osteoporosis, Postmenopausal

Vascular Function, Sarcopenia and Pain in Postmenopausal Osteoporosis

RECRUITING
NCT05228262Phase NAUniversity Hospital, Clermont-FerrandStarted 2022-02-15
Cohort follow-up
Type 1 Diabetes

Characterization of Autoreactive Regulatory and Conventional CD4 T Cells in Recent Onset Type 1 Diabetes and Control Individuals

RECRUITING
NCT06427421Phase NAAssistance Publique - Hôpitaux de ParisStarted 2025-05-06
Frequency of Treg and TeffsPhenotype of Treg and TeffsRNA seq analysis
Previously Treated Non-Small Cell Lung Cancer

Lung-MAP: A Master Screening Protocol for Previously-Treated Non-Small Cell Lung Cancer

RECRUITING
NCT03851445Phase PHASE2, PHASE3SWOG Cancer Research NetworkStarted 2019-02-06
Screening Platform
COVID-19 InfectionHematopoietic and Lymphatic System NeoplasmMalignant Solid Neoplasm

NCI COVID-19 in Cancer Patients, NCCAPS Study

ACTIVE NOT RECRUITING
NCT04387656National Cancer Institute (NCI)Started 2020-06-05
Biospecimen CollectionData CollectionQuality-of-Life Assessment
Retinitis Pigmentosa

Prospective Natural History Study of Retinitis Pigmentosa

ACTIVE NOT RECRUITING
NCT04285398Phase NASparingVisionStarted 2020-02-12
Ophthalmic examinationsMobility Test
16P11.2 Deletion Syndrome16p11.2 Duplications1Q21.1 Deletion

Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight

RECRUITING
NCT01238250Simons SearchlightStarted 2010-10
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗