GeneBe

CLIC5

chloride intracellular channel 5, the group of Chloride intracellular channels

Basic information

Region (hg38): 6:45880827-46080348

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

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Deafness, autosomal recessive 103ARAudiologic/OtolaryngologicEarly recognition and treatment of hearing impairment may improve outcomes, including speech and language developmentAudiologic/Otolaryngologic24781754

ClinVar

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

  • not_provided (84 variants)
  • not_specified (44 variants)
  • CLIC5-related_disorder (17 variants)
  • Autosomal_recessive_nonsyndromic_hearing_loss_103 (4 variants)
  • Hearing_loss,_autosomal_recessive (1 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. These statistics are base on transcript: NM_000016929.5. 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.

EffectPLPVUSLBBSum
synonymous
22
clinvar
1
clinvar
 23
missense
47
clinvar
12
clinvar
2
clinvar
 61
nonsense
1
clinvar
1
clinvar
1
clinvar
 3
start loss
0
frameshift
1
clinvar
 1
splice donor/acceptor (+/-2bp)
1
clinvar
 1
Total 2 1 49 34 3

Highest pathogenic variant AF is 0.00000124027

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
CLIC5protein_codingprotein_codingENST00000185206 6180088
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
0.000001620.6631257320131257450.0000517
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.5392092320.9000.00001292694
Missense in Polyphen7684.1210.90346918
Synonymous-0.56710799.81.070.00000609777
Loss of Function1.061115.50.7106.48e-7221

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0001230.000123
Ashkenazi Jewish0.00009920.0000992
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.00008070.0000791
Middle Eastern0.000.00
South Asian0.00003290.0000327
Other0.000.00

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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