CLIC2

chloride intracellular channel 2, the group of Chloride intracellular channels

Basic information

Region (hg38): X:155276211-155334657

Links

ENSG00000155962

∙ NCBI:1193 ∙ OMIM:300138 ∙ HGNC:2063 ∙ Uniprot:O15247 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

X-linked intellectual disability-cardiomegaly-congestive heart failure syndrome (Moderate), mode of inheritance: XL
X-linked intellectual disability-cardiomegaly-congestive heart failure syndrome (Disputed Evidence), mode of inheritance: XL
X-linked intellectual disability-cardiomegaly-congestive heart failure syndrome (Supportive), mode of inheritance: XL
X-linked intellectual disability-cardiomegaly-congestive heart failure syndrome (Limited), mode of inheritance: XL
X-linked intellectual disability-cardiomegaly-congestive heart failure syndrome (Limited), mode of inheritance: Unknown
X-linked complex neurodevelopmental disorder (Disputed Evidence), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, X-linked, syndromic 32	XL	Cardiovascular	Among other manifestations, individuals have been described as including cardiac findings such as atrial fibrillation, congestive heart failure, valvular insufficiency, and awareness may allow surveillance and early medical management	Cardiovascular; Musculoskeletal; Neurologic	22814392

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CLIC2 gene.

not_specified (25 variants)
not_provided (12 variants)
X-linked_intellectual_disability-cardiomegaly-congestive_heart_failure_syndrome (6 variants)
CLIC2-related_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CLIC2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001289.6. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	4 clinvar		5
missense			25 clinvar	5 clinvar		30
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	26	9	0

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CLIC2	protein_coding	protein_coding	ENST00000369449	6	58467

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0495	0.867	125735	1	3	125739	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.27	58	92.4	0.628	0.00000699	1632
Missense in Polyphen		14	41.398	0.33818		721
Synonymous	0.118	33	33.9	0.974	0.00000249	455
Loss of Function	1.43	3	7.13	0.421	4.46e-7	152

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000761	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000722	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000247	0.0000176
Middle Eastern	0.0000722	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Can insert into membranes and form chloride ion channels. Channel activity depends on the pH. Membrane insertion seems to be redox-regulated and may occur only under oxydizing conditions. Modulates the activity of RYR2 and inhibits calcium influx. {ECO:0000269|PubMed:15147738, ECO:0000269|PubMed:15916532, ECO:0000269|PubMed:17945253}.;
Disease: DISEASE: Mental retardation, X-linked, syndromic, 32 (MRXS32) [MIM:300886]: A mental retardation syndrome characterized by profound intellectual deficit, delayed psychomotor development beginning in infancy and little or no speech development. Additional features include seizures, large joint contractures, and abnormal positioning of the thumbs. Mental retardation is defined by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. {ECO:0000269|PubMed:22814392}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Pantoprazole Action Pathway;Rabeprazole Action Pathway;Esomeprazole Action Pathway;Omeprazole Action Pathway;Lansoprazole Action Pathway;Gastric Acid Production;Nizatidine Action Pathway;Cimetidine Action Pathway;Famotidine Action Pathway;Ranitidine Action Pathway;Betazole Action Pathway;Roxatidine acetate Action Pathway;Metiamide Action Pathway;Pirenzepine Action Pathway;Stimuli-sensing channels;Ion channel transport;Ion homeostasis;Transport of small molecules;Cardiac conduction;Muscle contraction (Consensus)

Recessive Scores

pRec: 0.140

Intolerance Scores

loftool: 0.140
rvis_EVS: 0.19
rvis_percentile_EVS: 66.57

Haploinsufficiency Scores

pHI: 0.226
hipred: N
hipred_score: 0.462
ghis: 0.537

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.903

Gene Damage Prediction

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

Gene ontology

Biological process: signal transduction;regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum;regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion;positive regulation of binding;negative regulation of ryanodine-sensitive calcium-release channel activity;cellular oxidant detoxification;chloride transmembrane transport
Cellular component: nucleus;cytoplasm;chloride channel complex
Molecular function: glutathione transferase activity;glutathione peroxidase activity;voltage-gated ion channel activity;chloride channel activity;protein binding