CLCA4 (chloride channel accessory 4)

Gene

• Entrez ID: 22802
• Gene name: Chloride channel accessory 4
• Gene symbol: CLCA4
• Synonyms (NCBI Gene): CaCC, CaCC2
• Chromosome: 1
• Chromosome location: 1p22.3
• Summary: The protein encoded by this gene belongs to the calcium sensitive chloride conductance protein family. To date, all members of this gene family map to the same site on chromosome 1p31-p22 and share high degrees of homology in size, sequence and predicted

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT018387	hsa-miR-335-5p	Microarray	18185580
MIRT022037	hsa-miR-128-3p	Microarray	17612493
MIRT894411	hsa-miR-4328	CLIP-seq
MIRT894412	hsa-miR-4645-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004222	Function	Metalloendopeptidase activity	IEA
GO:0004222	Function	Metalloendopeptidase activity	TAS
GO:0005229	Function	Intracellularly calcium-gated chloride channel activity	IBA
GO:0005229	Function	Intracellularly calcium-gated chloride channel activity	IEA
GO:0005254	Function	Chloride channel activity	IEA
GO:0005254	Function	Chloride channel activity	TAS	10437792
GO:0005576	Component	Extracellular region	IEA
GO:0005886	Component	Plasma membrane	IBA
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	TAS	10437792
GO:0006508	Process	Proteolysis	IEA
GO:0006821	Process	Chloride transport	IEA
GO:0008233	Function	Peptidase activity	IEA
GO:0008237	Function	Metallopeptidase activity	IEA
GO:0016020	Component	Membrane	IEA
GO:0016324	Component	Apical plasma membrane	IEA
GO:0016787	Function	Hydrolase activity	IEA
GO:0034220	Process	Monoatomic ion transmembrane transport	TAS
GO:0046872	Function	Metal ion binding	IEA
GO:1902476	Process	Chloride transmembrane transport	IEA

Other IDs

• MIM: 616857
• HGNC: 2018
• e!Ensembl: ENSG00000016602

Protein

• UniProt ID: Q14CN2
• Protein name: Calcium-activated chloride channel regulator 4 (EC 3.4.-.-) (Calcium-activated chloride channel family member 4) (hCLCA4) (Calcium-activated chloride channel protein 2) (CaCC-2) (hCaCC-2) (Chloride channel accessory 4) [Cleaved into: Calcium-activated chl
• Protein function: May be involved in mediating calcium-activated chloride conductance.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF08434	CLCA	24 → 289	Calcium-activated chloride channel N terminal	Family
  PF00092	VWA	307 → 472	von Willebrand factor type A domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Primarily expressed in the digestive tract, mainly in colon. Detected in smaller amounts in brain, urogenital organs, testis, and salivary and mammary glands. Highly expressed in the epithelial layer and submucosal gland of the inferio
• Sequence:

  MGLFRGFVFLLVLCLLHQSNTSFIKLNNNGFEDIVIVIDPSVPEDEKIIEQIEDMVTTAS
  TYLFEATEKRFFFKNVSILIPENWKENPQYKRPKHENHKHADVIVAPPTLPGRDEPYTKQ
  FTECGEKGEYIHFTPDLLLGKKQNEYGPPGKLFVHEWAHLRWGVFDEYNEDQPFYRAKSK
  KIEATRCSAGISGRNRVYKCQGGSCLSRACRIDSTTKLYGKDCQFFPDKVQTEKASIMFM
  QSIDSVVEFCNEKTHNQEAPSLQNIKCNFRSTWEVISNSEDFKNTIPMVTPPPPPVFSLL
  KISQRIVCLVLDKSGSMGGKDRLNRMNQAAKHFLLQTVENGSWVGMVHFDSTATIVNKLI
  QIKSSDERNTLMAGLPTYPLGGTSICSGIKYAFQVIGELHSQLDGSEVLLLTDGEDNTAS
  SCIDEVKQSGAIVHFIALGRAADEAVIEMSKITGGSHFYVSDEAQNNGLIDAFGALTSGN
  TDLSQKSLQLESKGLTLNSNAWMNDTVIIDSTVGKDTFFLITWNSLPPSISLWDPSGTIM
  ENFTVDATSKMAYLSIPGTAKVGTWAYNLQAKANPETLTITVTSRAANSSVPPITVNAKM
  NKDVNSFPSPMIVYAEILQGYVPVLGANVTAFIESQNGHTEVLELLDNGAGADSFKNDGV
  YSRYFTAYTENGRYSLKVRAHGGANTARLKLRPPLNRAAYIPGWVVNGEIEANPPRPEID
  EDTQTTLEDFSRTASGGAFVVSQVPSLPLPDQYPPSQITDLDATVHEDKIILTWTAPGDN
  FDVGKVQRYIIRISASILDLRDSFDDALQVNTTDLSPKEANSKESFAFKPENISEENATH
  IFIAIKSIDKSNLTSKVSNIAQVTLFIPQANPDDIDPTPTPTPTPTPDKSHNSGVNISTL
  VLSVIGSVVIVNFILSTTI

• Sequence length: 919

Pathways

KEGG:

Renin secretion
Pancreatic secretion

Reactome:

Stimuli-sensing channels

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Autism	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISTIC DISORDER	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CYSTIC FIBROSIS	—	Disgenet, GWAS catalog, Orphanet Disgenet, GWAS catalog, Orphanet Disgenet, GWAS catalog, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Anodontia	Anodontia	Pubtator	32773719	Associate	★☆☆☆☆ Found in Text Mining only
Azoospermia	Azoospermia	Pubtator	30887952	Associate	★☆☆☆☆ Found in Text Mining only
Biliary cirrhosis	Biliary cirrhosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Bladder Neoplasm	Bladder Neoplasm	BEFREE	29190973, 30847028		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	24386311		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	24386311	Inhibit	★☆☆☆☆ Found in Text Mining only
Carcinoma of bladder	Bladder carcinoma	BEFREE	29190973, 30847028		★☆☆☆☆ Found in Text Mining only
Colonic Neoplasms	Colonic neoplasm	Pubtator	36532007	Associate	★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	23593331, 31164625		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	23593331, 31137244, 35266369	Inhibit	★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	31164625, 32462020, 32773719, 32797167, 36991484	Associate	★☆☆☆☆ Found in Text Mining only
Cystic Fibrosis	Cystic Fibrosis	LHGDN	15490240		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cystic Fibrosis	Cystic Fibrosis	BEFREE	22205680, 23073314, 26474299		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cystic Fibrosis	Cystic Fibrosis	ORPHANET_DG	23073314		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cystic Fibrosis	Cystic fibrosis	Pubtator	23073314	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cystic fibrosis	Cystic Fibrosis	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Exocrine pancreatic insufficiency	Exocrine pancreatic insufficiency	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hepatic Encephalopathy	Hepatic Encephalopathy	BEFREE	20820037		★☆☆☆☆ Found in Text Mining only
Immunologic Deficiency Syndromes	Immunologic Deficiency Syndromes	HPO_DG			★☆☆☆☆ Found in Text Mining only
Infertility Male	Male infertility	Pubtator	23579007, 30887952, 32860660	Associate	★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	30312171		★☆☆☆☆ Found in Text Mining only
Lymphatic Metastasis	Lymphatic metastasis	Pubtator	31164625	Associate	★☆☆☆☆ Found in Text Mining only
Malabsorption Syndrome	Malabsorption Syndrome	HPO_DG			★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	24386311		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of urinary bladder	Urinary bladder cancer	BEFREE	29190973, 30847028		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	31164625		★☆☆☆☆ Found in Text Mining only
Mammary Neoplasms	Mammary Neoplasms	BEFREE	24386311		★☆☆☆☆ Found in Text Mining only
Mouth Neoplasms	Mouth neoplasm	Pubtator	25029526	Associate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	29190973, 30312171, 31164625		★☆☆☆☆ Found in Text Mining only
Non-obstructive azoospermia	Non-obstructive azoospermia	BEFREE	30887952		★☆☆☆☆ Found in Text Mining only
Pulmonary Fibrosis	Pulmonary Fibrosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Squamous Cell Carcinoma of Head and Neck	Squamous cell carcinoma	Pubtator	18254958	Inhibit	★☆☆☆☆ Found in Text Mining only