CLDN2

protein-coding

claudin 2, the group of Claudins

Gene summary

This gene product belongs to the claudin protein family whose members have been identified as major integral membrane proteins localized exclusively at tight junctions. Claudins are expressed in an organ-specific manner and regulate tissue-specific physiologic properties of tight junctions. This protein is expressed in the intestine. Alternatively spliced transcript variants with different 5' untranslated region have been found for this gene.[provided by RefSeq, Jan 2010]

MANE transcript

NM_020384.4

Inheritance

AD, XL

ClinVar variants

P:1U:30B:2

Top phenotype

Azoospermia, obstructive, with nephrolithiasis

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chrX:106,900,164-106,930,861

External References & Databases

Ensembl (ENSG00000165376)

Transcript & Mutation Effects

hg38 • Region Span ~30.7 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hereditary chronic pancreatitisLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0008185

Submitter: Ambry Genetics

azoospermia, obstructive, with nephrolithiasisLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0025356

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Azoospermia, obstructive, with nephrolithiasisXL

Manifestation: Genitourinary; Renal

Intervention: General

Rationale: 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

Refs: 31320686

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CLDN2 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 9

not providedTotal: 4

Male infertilityTotal: 1

Azoospermia, obstructive, with nephrolithiasisTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020384.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			7 clinvar	1 clinvar		8
missense	1 clinvar		23 clinvar	1 clinvar		25
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	1	0	30	2	0	33

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 17 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020384.4	RefSeq	NP_065117.1	1	MANE Select
ENST00000336803.2	Ensembl	ENSP00000336571.1	1	MANE Select
NM_001171092.1	RefSeq	NP_001164563.1	1	Standard
NM_001171095.2	RefSeq	NP_001164566.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cell adhesion molecules (CAMs) - Homo sapiens (human)
Tight junction - Homo sapiens (human)
Hepatitis C - Homo sapiens (human)
Leukocyte transendothelial migration - Homo sapiens (human)
Vitamin D Receptor Pathway

Biological Process

calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules

Molecular Function

structural molecule activity
protein binding
identical protein binding

Cellular Component

plasma membrane
bicellular tight junction
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000541806
Coding exons: 1
Length: 30698
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.61	44	86.2	0.511	0.00000609	1472
Missense (PolyPhen)		8	30.285	0.26416		528
Synonymous	0.831	29	35.3	0.822	0.00000254	509
Loss of Function	1.85	0	3.99	0.00	3.27e-7	60

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.107

Intolerance Scores

RVIS EVS: 0.15
RVIS percentile EVS: 64.11

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.781

Gene Damage Prediction

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