CLDN9

claudin 9, the group of Claudins

Basic information

Region (hg38): 16:3012923-3014505

Links

ENSG00000213937 ∙ NCBI:9080 ∙ OMIM:615799 ∙ HGNC:2051 ∙ Uniprot:O95484 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hearing loss, autosomal recessive 116 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive 116	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	Audiologic/Otolaryngologic	31175426

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CLDN9 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CLDN9 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				6	1	7
missense		1	37			38
nonsense						0
start loss						0
frameshift						0
inframe indel		1				1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	2	37	6	1

Variants in CLDN9

This is a list of pathogenic ClinVar variants found in the CLDN9 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-3013374-C-T			Likely benign (May 01, 2024)
16-3013375-G-A		not specified	Uncertain significance (Jun 09, 2022)
16-3013382-A-G		not specified	Uncertain significance (Dec 28, 2022)
16-3013385-T-C		not specified	Uncertain significance (Oct 08, 2024)
16-3013395-G-A		not specified	Uncertain significance (Apr 18, 2023)
16-3013429-G-A		not specified	Uncertain significance (Apr 22, 2024)
16-3013447-CT-C		Hearing loss, autosomal recessive 116	Pathogenic (Jul 22, 2024)
16-3013462-G-A		not specified	Uncertain significance (Oct 01, 2024)
16-3013499-T-G		not specified	Uncertain significance (Jun 09, 2022)
16-3013520-C-A		CLDN9-related disorder	Likely benign (Jun 26, 2024)
16-3013539-G-A			Likely benign (Mar 01, 2023)
16-3013558-G-C		not specified	Uncertain significance (Jan 02, 2024)
16-3013561-T-C		not specified	Uncertain significance (Dec 06, 2022)
16-3013584-G-A			Benign (Nov 01, 2024)
16-3013597-G-A		not specified	Uncertain significance (Oct 07, 2024)
16-3013603-C-T			Uncertain significance (May 01, 2023)
16-3013624-C-G		not specified	Uncertain significance (Sep 20, 2024)
16-3013670-A-G		not specified	Uncertain significance (Feb 23, 2023)
16-3013680-G-A			Likely benign (Dec 01, 2023)
16-3013681-T-C		not specified	Uncertain significance (Aug 19, 2024)
16-3013682-G-T		not specified	Uncertain significance (Apr 22, 2024)
16-3013692-C-G		not specified • CLDN9-related disorder	Uncertain significance (Mar 29, 2023)
16-3013697-G-A		not specified	Uncertain significance (Feb 23, 2023)
16-3013705-G-A		not specified	Uncertain significance (May 31, 2022)
16-3013708-C-T		Hearing loss, autosomal recessive 116	Likely pathogenic (May 01, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CLDN9	protein_coding	protein_coding	ENST00000445369	1	2050

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000631	0.156	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.08	179	143	1.26	0.00000928	1337
Missense in Polyphen		87	64.778	1.343		662
Synonymous	-2.42	100	73.6	1.36	0.00000518	522
Loss of Function	-0.654	7	5.37	1.30	2.33e-7	49

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	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
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}.
• 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)

Intolerance Scores

• loftool: 0.146
• rvis_EVS: -0.82
• rvis_percentile_EVS: 11.68

Haploinsufficiency Scores

• pHI: 0.208
• hipred: N
• hipred_score: 0.339
• ghis: 0.643

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.286

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cldn9
• Phenotype: hearing/vestibular/ear 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules;cell-cell junction organization;viral entry into host cell
• Cellular component: plasma membrane;bicellular tight junction;integral component of membrane;cell junction;intracellular membrane-bounded organelle
• Molecular function: virus receptor activity;structural molecule activity;protein binding;identical protein binding