CIC

capicua transcriptional repressor

Basic information

Region (hg38): 19:42268537-42295797

Links

ENSG00000079432 ∙ NCBI:23152 ∙ OMIM:612082 ∙ HGNC:14214 ∙ Uniprot:Q96RK0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Transcripts

Transcript IDs starting with ENST are treated as Ensembl, all others as RefSeq. Showing 4 of 48.

Transcript ID	Protein ID	Coding exons	MANE Select	MANE Plus Clinical
NM_001386298.1	NP_001373227.1	20	yes	-
ENST00000681038.1	ENSP00000505728.1	20	yes	-
NM_015125.5	NP_055940.3	20	-	-
NM_001304815.2	NP_001291744.1	20	-	-

Phenotypes

GenCC

Source: genCC

• complex neurodevelopmental disorder (Definitive), mode of inheritance: AD
• intellectual disability, autosomal dominant 45 (Definitive), mode of inheritance: AD
• intellectual disability, autosomal dominant 45 (Strong), mode of inheritance: AD
• autosomal dominant non-syndromic intellectual disability (Supportive), mode of inheritance: AD
• intellectual disability, autosomal dominant 45 (Strong), mode of inheritance: AD
• cerebral folate deficiency (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal dominant 45	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	28288114

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CIC gene.

• not_provided (414 variants)
• Inborn_genetic_diseases (254 variants)
• Intellectual_disability,_autosomal_dominant_45 (157 variants)
• CIC-related_disorder (112 variants)
• not_specified (108 variants)
• Intellectual_disability (7 variants)
• See_cases (7 variants)
• Autism_spectrum_disorder (4 variants)
• Neurodevelopmental_disorder_with_hypotonia,_seizures,_and_absent_language (3 variants)
• Neurodevelopmental_disorder (2 variants)
• CIC-related_neurodevelopmental_disorders (2 variants)
• Intellectual_disability,_autosomal_dominant_1 (2 variants)
• Familial_thoracic_aortic_aneurysm_and_aortic_dissection (1 variants)
• Neurodevelopmental_delay (1 variants)
• Hearing_impairment (1 variants)
• Hereditary_ataxia (1 variants)
• Marfanoid_habitus_and_intellectual_disability (1 variants)
• EBV-positive_nodal_T-_and_NK-cell_lymphoma (1 variants)
• Autosomal_dominant_non-syndromic_intellectual_disability (1 variants)
• Congenital_cerebellar_hypoplasia (1 variants)
• NK-cell_enteropathy (1 variants)
• Dias-Logan_syndrome (1 variants)
• Intellectual_developmental_disorder_with_behavioral_abnormalities_and_craniofacial_dysmorphism_with_or_without_seizures (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CIC gene is commonly pathogenic or not. These statistics are base on transcript: NM_001386298.1. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	13	155	7	176
missense	1	14	467	124	6	612
nonsense	6	10	10	1		27
start loss						0
frameshift	21	26	13			60
splice donor/acceptor (+/-2bp)	1	5	12			18
Total	29	56	515	280	13

Highest pathogenic variant AF is 0.00000821145

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CIC	protein_coding	protein_coding	ENST00000575354	20	27261

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125739	0	9	125748	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.726	904	968	0.934	0.0000644	9995
Missense in Polyphen		305	422.99	0.72107		4198
Synonymous	-4.48	545	427	1.28	0.0000297	3758
Loss of Function	6.02	4	49.9	0.0801	0.00000259	602

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000149	0.000148
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000548	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000356	0.0000352
Middle Eastern	0.0000548	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcriptional repressor which plays a role in development of the central nervous system (CNS). In concert with ATXN1 and ATXN1L, involved in brain development. {ECO:0000250|UniProtKB:Q924A2}.

Recessive Scores

• pRec: 0.176

Intolerance Scores

• loftool: 0.0161
• rvis_EVS: -3.38
• rvis_percentile_EVS: 0.38

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.757

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Zebrafish Information Network

• Gene name: cicb
• Affected structure: primitive erythrocyte differentiation
• Phenotype tag: abnormal
• Phenotype quality: increased occurrence

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;brain development;learning;memory;social behavior;negative regulation of transcription, DNA-templated;lung alveolus development
• Cellular component: nucleus;nucleoplasm;protein-containing complex;intracellular membrane-bounded organelle
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;chromatin binding;protein binding