CLIC5

chloride intracellular channel 5, the group of Chloride intracellular channels

Basic information

Region (hg38): 6:45880826-46080348

Links

ENSG00000112782 ∙ NCBI:53405 ∙ OMIM:607293 ∙ HGNC:13517 ∙ Uniprot:Q9NZA1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive nonsyndromic hearing loss 103 (Moderate), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 103 (Limited), mode of inheritance: AR
• hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 103 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive 103	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic	24781754

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CLIC5 gene.

• not provided (103 variants)
• not specified (25 variants)
• Inborn genetic diseases (8 variants)
• Autosomal recessive nonsyndromic hearing loss 103 (2 variants)
• - (2 variants)
• Hearing impairment (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CLIC5 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				23	3	26
missense			27	10	6	43
nonsense			3			3
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				3	1	4
non coding				10	18	28
Total	0	0	30	43	27

Variants in CLIC5

This is a list of pathogenic ClinVar variants found in the CLIC5 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-45903093-A-C		not specified	Uncertain significance (Oct 22, 2023)
6-45903096-G-A			Uncertain significance (Apr 13, 2022)
6-45903105-G-A		not specified • CLIC5-related disorder	Conflicting classifications of pathogenicity (Nov 26, 2023)
6-45903121-G-A			Likely benign (Jul 26, 2023)
6-45903147-C-T		not specified	Uncertain significance (Aug 14, 2023)
6-45903148-T-A		not specified	Benign (Oct 22, 2023)
6-45903173-C-T			Uncertain significance (Jan 04, 2024)
6-45903197-C-T		not specified	Uncertain significance (Aug 03, 2022)
6-45903200-C-T		Hearing loss, autosomal recessive	Likely pathogenic (Jun 23, 2017)
6-45903220-C-T			Likely benign (May 11, 2018)
6-45903229-A-G			Likely benign (Mar 03, 2023)
6-45903230-T-C		Hearing impairment	Uncertain significance (Apr 12, 2021)
6-45903233-T-G		not specified	Uncertain significance (May 15, 2023)
6-45903236-C-T		not specified	Uncertain significance (Jun 03, 2022)
6-45903247-G-A			Likely benign (Nov 18, 2021)
6-45903262-CAG-C		not specified	Benign (Jan 31, 2024)
6-45903461-C-T			Likely benign (Mar 19, 2019)
6-45912436-A-G			Likely benign (Nov 10, 2018)
6-45912574-T-C			Benign (Nov 10, 2018)
6-45912742-A-G		not specified • CLIC5-related disorder	Benign (Jul 24, 2019)
6-45912748-A-G		not specified • CLIC5-related disorder	Benign (Jul 24, 2019)
6-45914243-C-T			Likely benign (Apr 10, 2022)
6-45914257-T-G			Uncertain significance (Dec 24, 2021)
6-45914263-C-T			Uncertain significance (Jun 19, 2023)
6-45914301-C-T		not specified	Benign (Nov 20, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CLIC5	protein_coding	protein_coding	ENST00000185206	6	180088

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000162	0.663	125732	0	13	125745	0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.539	209	232	0.900	0.0000129	2694
Missense in Polyphen		76	84.121	0.90346		918
Synonymous	-0.567	107	99.8	1.07	0.00000609	777
Loss of Function	1.06	11	15.5	0.710	6.48e-7	221

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000123	0.000123
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000807	0.0000791
Middle Eastern	0.00	0.00
South Asian	0.0000329	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for normal hearing (PubMed:24781754). It is necessary for the formation of stereocilia in the inner ear and normal development of the organ of Corti (By similarity). Can insert into membranes and form poorly selective ion channels that may also transport chloride ions. May play a role in the regulation of transepithelial ion absorption and secretion. Is required for the development and/or maintenance of the proper glomerular endothelial cell and podocyte architecture (PubMed:15184393, PubMed:18028448, PubMed:20335315). {ECO:0000250|UniProtKB:Q8BXK9, ECO:0000269|PubMed:15184393, ECO:0000269|PubMed:18028448, ECO:0000269|PubMed:20335315, ECO:0000269|PubMed:24781754}.
• Disease: DISEASE: Deafness, autosomal recessive, 103 (DFNB103) [MIM:616042]: A form of sensorineural deafness with onset in early childhood. Hearing impairment progresses from mild to severe or even profound before the second decade, and is accompanied by vestibular areflexia. {ECO:0000269|PubMed:24781754}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.0942

Intolerance Scores

• loftool: 0.153
• rvis_EVS: 1.02
• rvis_percentile_EVS: 90.98

Haploinsufficiency Scores

• pHI: 0.256
• hipred: Y
• hipred_score: 0.583
• ghis: 0.401

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.457

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Clic5
• Phenotype: hearing/vestibular/ear phenotype; 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); respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: chloride transport;female pregnancy;sensory perception of sound;regulation of ion transmembrane transport;chloride transmembrane transport
• Cellular component: Golgi apparatus;microtubule organizing center;cell cortex;actin cytoskeleton;chloride channel complex;extracellular exosome
• Molecular function: voltage-gated ion channel activity;chloride channel activity;protein binding