CLCA2

chloride channel accessory 2, the group of Chloride channel accessory

Basic information

Region (hg38): 1:86424171-86456553

Links

ENSG00000137975 ∙ NCBI:9635 ∙ OMIM:604003 ∙ HGNC:2016 ∙ Uniprot:Q9UQC9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• heart conduction disease (Moderate), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CLCA2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CLCA2 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				2	3	5
missense			60	6		66
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding						0
Total	0	0	60	8	3

Variants in CLCA2

This is a list of pathogenic ClinVar variants found in the CLCA2 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-86424281-A-G		not specified	Likely benign (Dec 27, 2022)
1-86424293-G-T		not specified	Uncertain significance (Aug 02, 2021)
1-86424299-C-G		not specified	Uncertain significance (Sep 27, 2021)
1-86424357-A-T		not specified	Uncertain significance (Oct 24, 2023)
1-86424398-G-A		not specified	Uncertain significance (Jul 13, 2022)
1-86425384-A-G		not specified	Uncertain significance (Feb 16, 2023)
1-86428451-C-T		not specified	Uncertain significance (May 31, 2023)
1-86428452-A-G		not specified	Uncertain significance (Dec 05, 2022)
1-86428469-A-G		not specified	Uncertain significance (Feb 27, 2024)
1-86428558-C-T			Benign (Oct 11, 2018)
1-86428566-G-A		not specified	Uncertain significance (Dec 19, 2023)
1-86428566-G-C		not specified	Uncertain significance (May 24, 2023)
1-86430865-G-A		not specified	Uncertain significance (Jun 18, 2021)
1-86430883-G-C		not specified	Uncertain significance (Sep 26, 2022)
1-86430891-C-T		not specified	Uncertain significance (Nov 05, 2021)
1-86430908-C-T			Likely benign (Oct 11, 2018)
1-86430922-A-G		not specified	Uncertain significance (Dec 01, 2022)
1-86432365-T-G			Likely benign (Aug 01, 2023)
1-86432419-C-G		not specified	Uncertain significance (Jan 17, 2024)
1-86434518-G-T		not specified	Uncertain significance (Nov 01, 2022)
1-86434542-A-G		not specified	Uncertain significance (Nov 09, 2023)
1-86434581-T-C		not specified	Uncertain significance (Apr 18, 2023)
1-86434629-C-T		not specified	Uncertain significance (Feb 11, 2022)
1-86434665-C-T		not specified	Uncertain significance (Aug 16, 2022)
1-86434681-C-T		not specified	Uncertain significance (Jul 19, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CLCA2	protein_coding	protein_coding	ENST00000370565	14	32473

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.47e-28	0.000138	125577	1	170	125748	0.000680

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.373	469	492	0.953	0.0000236	6191
Missense in Polyphen		139	160.23	0.8675		2086
Synonymous	-1.76	204	174	1.17	0.00000840	1819
Loss of Function	0.0804	43	43.6	0.987	0.00000254	490

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00161	0.00161
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000381	0.000381
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000867	0.000862
Middle Eastern	0.000381	0.000381
South Asian	0.000790	0.000752
Other	0.000658	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role in modulating chloride current across the plasma membrane in a calcium-dependent manner, and cell adhesion. Involved in basal cell adhesion and/or stratification of squamous epithelia. May act as a tumor suppressor in breast and colorectal cancer. Plays a key role for cell adhesion in the beginning stages of lung metastasis via the binding to ITGB4. {ECO:0000269|PubMed:10554024, ECO:0000269|PubMed:11320086, ECO:0000269|PubMed:11445004, ECO:0000269|PubMed:15707651, ECO:0000269|PubMed:16158324}.
• Pathway: Renin secretion - Homo sapiens (human);Pancreatic secretion - Homo sapiens (human);Stimuli-sensing channels;Ion channel transport;p73 transcription factor network;Transport of small molecules;Validated transcriptional targets of TAp63 isoforms (Consensus)

Recessive Scores

• pRec: 0.157

Intolerance Scores

• loftool: 0.966
• rvis_EVS: -0.04
• rvis_percentile_EVS: 50.54

Haploinsufficiency Scores

• pHI: 0.178
• hipred: N
• hipred_score: 0.153
• ghis: 0.471

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0361

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Clca2
• Phenotype: liver/biliary system phenotype

Gene ontology

• Biological process: proteolysis;cell adhesion;ion transmembrane transport;chloride transmembrane transport
• Cellular component: extracellular region;nucleus;cytosol;plasma membrane;integral component of plasma membrane;basal plasma membrane;cell junction;nuclear membrane
• Molecular function: metalloendopeptidase activity;intracellular calcium activated chloride channel activity;chloride channel activity;ligand-gated ion channel activity;metal ion binding