CLDN19

claudin 19, the group of Claudins

Basic information

Region (hg38): 1:42733093-42740254

Links

ENSG00000164007 ∙ NCBI:149461 ∙ OMIM:610036 ∙ HGNC:2040 ∙ Uniprot:Q8N6F1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• renal hypomagnesemia 5 with ocular involvement (Definitive), mode of inheritance: AR
• renal hypomagnesemia 5 with ocular involvement (Strong), mode of inheritance: AR
• renal hypomagnesemia 5 with ocular involvement (Strong), mode of inheritance: AR
• renal hypomagnesemia 5 with ocular involvement (Strong), mode of inheritance: AR
• renal hypomagnesemia 5 with ocular involvement (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypomagnesemia 5, renal, with or without ocular involvement	AR	Renal	Electrolyte replacement and surveillance for sequelae such as urinary tract infections can be beneficial	Ophthalmologic; Renal	500385; 7947033; 17033971; 21030577; 21791920; 22422540; 23301036; 23538362

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CLDN19 gene.

• not_provided (84 variants)
• Renal_hypomagnesemia_5_with_ocular_involvement (71 variants)
• Inborn_genetic_diseases (35 variants)
• CLDN19-related_disorder (7 variants)
• Nephrocalcinosis (1 variants)
• Renal_Hypomagnesemia,_Recessive (1 variants)
• not_specified (1 variants)
• Nephrolithiasis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CLDN19 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000148960.3. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	26		27
missense	4	11	62	4	1	82
nonsense	3	1	1			5
start loss						0
frameshift	1	3	1			5
splice donor/acceptor (+/-2bp)	1	2	1			4
Total	9	17	66	30	1

Highest pathogenic variant AF is 0.000023451801

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CLDN19	protein_coding	protein_coding	ENST00000296387	5	7162

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00497	0.895	125695	0	5	125700	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.779	112	138	0.813	0.00000866	1389
Missense in Polyphen		44	58.186	0.75619		590
Synonymous	1.46	49	63.8	0.768	0.00000461	497
Loss of Function	1.40	5	9.71	0.515	4.17e-7	108

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000950	0.0000924
European (Non-Finnish)	0.0000179	0.0000176
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. {ECO:0000250|UniProtKB:Q9ET38}.
• Disease: DISEASE: Hypomagnesemia 5, renal, with or without ocular involvement (HOMG5) [MIM:248190]: A progressive renal disease characterized by primary renal magnesium wasting with hypomagnesemia, hypercalciuria and nephrocalcinosis associated with severe ocular abnormalities such as bilateral chorioretinal scars, macular colobomata, significant myopia and nystagmus. The renal phenotype is virtually undistinguishable from that of patients with HOMG3. {ECO:0000269|PubMed:17033971}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• 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: 0.142

Intolerance Scores

• loftool: 0.0854
• rvis_EVS: 0.68
• rvis_percentile_EVS: 84.93

Haploinsufficiency Scores

• pHI: 0.177
• hipred: N
• hipred_score: 0.444
• ghis: 0.496

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.269

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cldn19
• Phenotype: homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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)

Gene ontology

• Biological process: visual perception;calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules;neuronal action potential propagation;apical junction assembly;response to stimulus
• Cellular component: nucleus;cytoplasm;bicellular tight junction;integral component of membrane;basolateral plasma membrane;apical junction complex
• Molecular function: structural molecule activity;identical protein binding