CLDN16

claudin 16, the group of Claudins

Basic information

Region (hg38): 3:190322540-190412138

Links

ENSG00000113946 ∙ NCBI:10686 ∙ OMIM:603959 ∙ HGNC:2037 ∙ Uniprot:Q9Y5I7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• renal hypomagnesemia 3 (Strong), mode of inheritance: AR
• renal hypomagnesemia 3 (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypomagnesemia 3, renal	AR	Renal	Presentation can include hypocalcemic/hypomagnesemic seizures, and early diagnosis and magnesium therapy can be beneficial; Renal transplantation is frequently necessary	Renal	668721; 7637271; 9579153; 10390358; 10878661; 14628289; 16501001; 20607983; 21669885; 21848011; 22422540
Some individuals have a self-limiting form of disease

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CLDN16 gene.

• Primary hypomagnesemia (92 variants)
• not provided (86 variants)
• Inborn genetic diseases (14 variants)
• not specified (3 variants)
• Nephrolithiasis;Nephrocalcinosis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CLDN16 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			4	14		18
missense	3	8	34	1	2	48
nonsense	1	1				2
start loss	1		1			2
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region			1	3		4
non coding			46	19	18	83
Total	5	10	86	34	20

Highest pathogenic variant AF is 0.0000197

Variants in CLDN16

This is a list of pathogenic ClinVar variants found in the CLDN16 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-190322608-C-T			Benign (Nov 10, 2018)
3-190322650-C-A			Benign (Nov 10, 2018)
3-190322667-G-A			Benign (Nov 10, 2018)
3-190387530-G-A			Benign (Aug 20, 2019)
3-190387611-A-G			Benign (Nov 10, 2018)
3-190387662-C-T			Benign (Aug 20, 2019)
3-190387914-G-T		Primary hypomagnesemia	Uncertain significance (Mar 16, 2018)
3-190387965-C-T		Primary hypomagnesemia	Uncertain significance (Jan 13, 2018)
3-190387984-T-C		Primary hypomagnesemia	Uncertain significance (Jan 13, 2018)
3-190388038-A-G		Primary hypomagnesemia	Uncertain significance (Jan 13, 2018)
3-190388079-C-T		Primary hypomagnesemia	Likely benign (Jan 12, 2018)
3-190388114-C-T		Primary hypomagnesemia	Uncertain significance (Jan 12, 2018)
3-190388115-G-A		Primary hypomagnesemia	Uncertain significance (Jan 13, 2018)
3-190388117-A-T		Primary hypomagnesemia • CLDN16-related disorder	Conflicting classifications of pathogenicity (Aug 23, 2022)
3-190388141-T-C			Likely benign (Jun 13, 2022)
3-190388146-T-C			Likely benign (Jun 23, 2023)
3-190388154-GT-G		Primary hypomagnesemia	Uncertain significance (Apr 27, 2017)
3-190388181-G-T			Uncertain significance (Jun 28, 2022)
3-190388185-CCTG-C			Uncertain significance (Sep 16, 2018)
3-190388190-A-G		Inborn genetic diseases	Likely benign (Dec 07, 2023)
3-190388196-G-A		Inborn genetic diseases	Uncertain significance (May 24, 2021)
3-190388198-G-A		Primary hypomagnesemia	Uncertain significance (Nov 27, 2021)
3-190388214-G-T		Primary hypomagnesemia • Inborn genetic diseases	Uncertain significance (Jun 21, 2023)
3-190388226-C-T			Uncertain significance (Nov 14, 2022)
3-190388232-G-A			Uncertain significance (Feb 02, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CLDN16	protein_coding	protein_coding	ENST00000264734	5	89603

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0255	0.963	125738	0	10	125748	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0768	173	170	1.02	0.00000962	1957
Missense in Polyphen		54	58.51	0.92293		693
Synonymous	-1.25	79	66.1	1.20	0.00000410	626
Loss of Function	2.21	5	13.9	0.360	7.51e-7	160

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000152	0.000152
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000528	0.0000527
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium- independent cell-adhesion activity. Involved in paracellular magnesium reabsorption. Required for a selective paracellular conductance. May form, alone or in partnership with other constituents, an intercellular pore permitting paracellular passage of magnesium and calcium ions down their electrochemical gradients. Alternatively, it could be a sensor of magnesium concentration that could alter paracellular permeability mediated by other factors.
• Pathway: Cell adhesion molecules (CAMs) - Homo sapiens (human);Tight junction - Homo sapiens (human);Hepatitis C - Homo sapiens (human);Leukocyte transendothelial migration - Homo sapiens (human);EMT transition in Colorectal Cancer;Tight junction interactions;Cell-cell junction organization;Cell junction organization;Cell-Cell communication (Consensus)

Recessive Scores

• pRec: 0.194

Intolerance Scores

• loftool: 0.145
• rvis_EVS: -0.14
• rvis_percentile_EVS: 43.57

Haploinsufficiency Scores

• pHI: 0.259
• hipred: N
• hipred_score: 0.460
• ghis: 0.402

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.265

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cldn16
• Phenotype: renal/urinary system phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: cellular metal ion homeostasis;excretion;calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules;magnesium ion transmembrane transport
• Cellular component: plasma membrane;bicellular tight junction;integral component of membrane
• Molecular function: structural molecule activity;protein binding;magnesium ion transmembrane transporter activity;identical protein binding