CIC

capicua transcriptional repressor

Basic information

Region (hg38): 19:42268536-42295797

Links

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

Phenotypes

GenCC

Source: genCC

• cerebral folate deficiency (Strong), mode of inheritance: AD
• intellectual disability, autosomal dominant 45 (Strong), 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 (Definitive), 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 (250 variants)
• Intellectual disability, autosomal dominant 45 (93 variants)
• Inborn genetic diseases (75 variants)
• not specified (47 variants)
• CIC-related condition (20 variants)
• See cases (7 variants)
• Autism spectrum disorder (4 variants)
• CIC-related neurodevelopmental disorders (2 variants)
• Neurodevelopmental disorder (2 variants)
• Neurodevelopmental delay (1 variants)
• Seizure;Intellectual disability (1 variants)
• Intellectual disability (1 variants)
• Marfanoid habitus and intellectual disability (1 variants)
• Seizure (1 variants)
• NK-cell enteropathy (1 variants)
• Autosomal dominant non-syndromic intellectual disability (1 variants)
• Intellectual disability, autosomal dominant 1 (1 variants)
• Dias-Logan syndrome;Intellectual disability, autosomal dominant 45 (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	4	79	13	97
missense	1	6	202	59	8	276
nonsense	3	7	5			15
start loss						0
frameshift	11	9	5			25
inframe indel			4	1		5
splice donor/acceptor (+/-2bp)	1	3	1			5
splice region			3	2	1	6
non coding				3	2	5
Total	16	26	221	142	23

Highest pathogenic variant AF is 0.00000657

Variants in CIC

This is a list of pathogenic ClinVar variants found in the CIC region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-42271833-G-T		CIC-related disorder	Uncertain significance (Oct 20, 2022)
19-42271848-C-T		CIC-related disorder	Benign (Jan 01, 2024)
19-42271875-G-A		Intellectual disability, autosomal dominant 45	Uncertain significance (May 03, 2020)
19-42271877-C-T		Intellectual disability, autosomal dominant 45	Uncertain significance (Nov 10, 2023)
19-42271892-GGT-G		Intellectual disability, autosomal dominant 45	Likely pathogenic (Mar 31, 2022)
19-42271898-A-C			Uncertain significance (Aug 11, 2022)
19-42271916-G-A		not specified	Conflicting classifications of pathogenicity (Jun 01, 2022)
19-42271918-C-T			Likely benign (May 01, 2022)
19-42271919-G-A		CIC-related disorder	Likely benign (Jan 01, 2024)
19-42271945-C-T		CIC-related disorder	Likely benign (May 15, 2019)
19-42271946-G-A		CIC-related disorder	Uncertain significance (Nov 06, 2023)
19-42271959-C-G			Uncertain significance (Sep 01, 2022)
19-42271981-G-T			Uncertain significance (Feb 01, 2024)
19-42271989-G-A		Intellectual disability, autosomal dominant 45 • CIC-related disorder	Conflicting classifications of pathogenicity (Feb 22, 2019)
19-42272009-C-A		Intellectual disability, autosomal dominant 45	Uncertain significance (Oct 19, 2020)
19-42272032-C-T			Likely benign (Oct 01, 2022)
19-42272038-G-A			Likely benign (Nov 01, 2023)
19-42272064-A-G		Intellectual disability, autosomal dominant 45	Conflicting classifications of pathogenicity (Feb 01, 2024)
19-42272065-AGGGGAT-A		CIC-related disorder	Uncertain significance (Oct 28, 2022)
19-42272085-G-A		CIC-related disorder	Likely benign (Oct 04, 2023)
19-42272088-G-A			Uncertain significance (Jul 01, 2022)
19-42272137-CAAG-C		not specified	Uncertain significance (Jan 23, 2024)
19-42272177-G-C			Uncertain significance (Nov 01, 2023)
19-42272202-G-A			Likely benign (Feb 01, 2023)
19-42272208-G-A		Intellectual disability, autosomal dominant 45	Uncertain significance (Jun 12, 2020)

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
1.00	0.0000102	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

Haploinsufficiency Scores

• pHI: 0.236
• hipred: Y
• hipred_score: 0.598
• ghis: 0.626

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

Mouse Genome Informatics

• Gene name: Cic
• Phenotype: respiratory system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); growth/size/body region phenotype

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