CLCN3
chloride voltage-gated channel 3, the group of Chloride voltage-gated channels
Basic information
Region (hg38): 4:169612633-169723673
Links
Phenotypes
GenCC
Source:
- complex neurodevelopmental disorder (Strong), mode of inheritance: AD
- neurodevelopmental disorder with hypotonia and brain abnormalities (Moderate), mode of inheritance: AD
- neurodevelopmental disorder with seizures and brain abnormalities (Limited), mode of inheritance: AR
- neurodevelopmental disorder with seizures and brain abnormalities (Limited), mode of inheritance: AR
- neurodevelopmental disorder with hypotonia and brain abnormalities (Strong), mode of inheritance: AD
- neurodevelopmental disorder with hypotonia and brain abnormalities (Strong), mode of inheritance: AD
- neurodevelopmental disorder with seizures and brain abnormalities (Limited), mode of inheritance: AR
- neurodevelopmental disorder with hypotonia and brain abnormalities (Moderate), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Neurodevelopmental disorder with hypotonia and brain abnormalities; Neurodevelopmental disorder with seizures and brain abnormalities | AD/AR | 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 | Craniofacial; Neurologic; Ophthalmologic | 34186028 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (59 variants)
- Inborn_genetic_diseases (57 variants)
- Neurodevelopmental_disorder_with_hypotonia_and_brain_abnormalities (31 variants)
- CLCN3-related_disorder (10 variants)
- Neurodevelopmental_delay (9 variants)
- Neurodevelopmental_disorder_with_seizures_and_brain_abnormalities (4 variants)
- Neurodevelopmental_disorder (1 variants)
- CLCN3-related_neurodevelopmental_disorders (1 variants)
- Progressive_sensorineural_hearing_impairment (1 variants)
- Autism,_susceptiblity_to (1 variants)
- Complex_neurodevelopmental_disorder (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CLCN3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001829.4. 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 | 6 | |||||
| missense | 13 | 113 | 129 | |||
| nonsense | 3 | |||||
| start loss | 0 | |||||
| frameshift | 5 | |||||
| splice donor/acceptor (+/-2bp) | 3 | |||||
| Total | 2 | 13 | 123 | 8 | 0 |
Highest pathogenic variant AF is 0.0000020599812
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| CLCN3 | protein_coding | protein_coding | ENST00000347613 | 13 | 111041 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.000266 | 125734 | 0 | 14 | 125748 | 0.0000557 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 4.37 | 208 | 477 | 0.436 | 0.0000240 | 5660 |
| Missense in Polyphen | 90 | 243.58 | 0.36949 | 3026 | ||
| Synonymous | 1.47 | 147 | 171 | 0.857 | 0.00000928 | 1682 |
| Loss of Function | 5.37 | 4 | 41.2 | 0.0971 | 0.00000220 | 488 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000916 | 0.0000913 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.0000462 | 0.0000462 |
| European (Non-Finnish) | 0.0000618 | 0.0000615 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.0000654 | 0.0000653 |
| Other | 0.000163 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Mediates the exchange of chloride ions against protons. Functions as antiporter and contributes to the acidification of the endosome and synaptic vesicle lumen, and may thereby affect vesicle trafficking and exocytosis. May play an important role in neuronal cell function through regulation of membrane excitability by protein kinase C. It could help neuronal cells to establish short-term memory. {ECO:0000269|PubMed:11967229}.;
- Pathway
- Stimuli-sensing channels;Ion channel transport;Transport of small molecules
(Consensus)
Recessive Scores
- pRec
- 0.245
Intolerance Scores
- loftool
- 0.0597
- rvis_EVS
- -0.58
- rvis_percentile_EVS
- 18.59
Haploinsufficiency Scores
- pHI
- 0.486
- hipred
- Y
- hipred_score
- 0.825
- ghis
- 0.598
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.945
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Clcn3
- Phenotype
- adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; muscle phenotype; renal/urinary system phenotype; skeleton phenotype; immune system phenotype; homeostasis/metabolism phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); reproductive 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); vision/eye phenotype; digestive/alimentary 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);
Gene ontology
- Biological process
- regulation of pH;negative regulation of cell volume;endosomal lumen acidification;synaptic vesicle lumen acidification;chloride transmembrane transport
- Cellular component
- Golgi membrane;endosome;early endosome;late endosome;Golgi apparatus;plasma membrane;integral component of plasma membrane;synaptic vesicle;external side of plasma membrane;cell surface;vesicle membrane;membrane;integral component of membrane;secretory granule;transport vesicle membrane;cytoplasmic vesicle;early endosome membrane;late endosome membrane;specific granule;phagocytic vesicle
- Molecular function
- voltage-gated chloride channel activity;chloride channel activity;protein binding;ATP binding;solute:proton antiporter activity;PDZ domain binding;chloride ion binding;protein homodimerization activity;protein heterodimerization activity;volume-sensitive chloride channel activity