CDH3

cadherin 3, the group of Type I classical cadherins

Basic information

Region (hg38): 16:68636188-68727468

Links

ENSG00000062038 ∙ NCBI:1001 ∙ OMIM:114021 ∙ HGNC:1762 ∙ Uniprot:P22223 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• EEM syndrome (Definitive), mode of inheritance: AR
• congenital hypotrichosis with juvenile macular dystrophy (Supportive), mode of inheritance: AR
• EEM syndrome (Supportive), mode of inheritance: AR
• EEM syndrome (Strong), mode of inheritance: AR
• congenital hypotrichosis with juvenile macular dystrophy (Strong), mode of inheritance: AR
• EEM syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypotrichosis, congenital, with juvenile macular dystrophy; Ectodermal dysplasia, ectrodactyly, and macular dystrophy syndrome	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	Dermatologic; Musculoskeletal; Ophthalmologic	13372143; 10420194; 11544476; 12445216; 15805154; 20140736; 22140374; 22348569; 23143461
Heterozygotes may display subtle effects

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CDH3 gene.

• not provided (635 variants)
• EEM syndrome (108 variants)
• Inborn genetic diseases (31 variants)
• Congenital hypotrichosis with juvenile macular dystrophy (16 variants)
• not specified (9 variants)
• Congenital hypotrichosis with juvenile macular dystrophy;EEM syndrome (3 variants)
• Malignant tumor of prostate (1 variants)
• Retinitis pigmentosa (1 variants)
• Macular dystrophy (1 variants)
• CDH3-related condition (1 variants)
• Retinal dystrophy (1 variants)
• Hypotrichosis with juvenile macular dystrophy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CDH3 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			10	130	11	151
missense	1	2	289	8	4	304
nonsense	7					7
start loss						0
frameshift	12	1	2			15
inframe indel			6			6
splice donor/acceptor (+/-2bp)	2	10				12
splice region		1	14	19		34
non coding			27	72	25	124
Total	22	13	334	210	40

Highest pathogenic variant AF is 0.0000131

Variants in CDH3

This is a list of pathogenic ClinVar variants found in the CDH3 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-68644295-A-G		EEM syndrome	Uncertain significance (Jun 14, 2016)
16-68644397-A-G		EEM syndrome	Uncertain significance (Jun 14, 2016)
16-68644701-T-C		EEM syndrome	Uncertain significance (Jun 14, 2016)
16-68644734-C-CA		EEM syndrome	Uncertain significance (Jun 14, 2016)
16-68644735-C-CA		EEM syndrome	Benign (Jun 14, 2016)
16-68644745-AAAAAAAG-A		EEM syndrome	Uncertain significance (Jun 14, 2016)
16-68644745-A-AG		EEM syndrome	Uncertain significance (Jun 14, 2016)
16-68644746-A-AG		EEM syndrome	Uncertain significance (Jun 14, 2016)
16-68644752-G-A		EEM syndrome	Uncertain significance (Jun 14, 2016)
16-68644759-G-A		EEM syndrome	Uncertain significance (Jun 14, 2016)
16-68644843-A-G		EEM syndrome	Benign (Jun 14, 2016)
16-68644981-G-C		EEM syndrome	Likely benign (Jun 14, 2016)
16-68645078-C-T		EEM syndrome	Uncertain significance (Jun 14, 2016)
16-68645098-G-T		EEM syndrome	Uncertain significance (Jun 14, 2016)
16-68645113-C-T		EEM syndrome	Uncertain significance (Jun 14, 2016)
16-68645187-G-T		EEM syndrome	Uncertain significance (Jun 14, 2016)
16-68645239-C-G		EEM syndrome	Uncertain significance (Jun 14, 2016)
16-68645240-G-T		EEM syndrome	Uncertain significance (Jun 14, 2016)
16-68645308-T-C		EEM syndrome	Uncertain significance (Jun 14, 2016)
16-68645344-C-T		EEM syndrome	Uncertain significance (Jan 12, 2018)
16-68645365-CCT-C		CDH3-related disorder	Likely benign (Aug 06, 2019)
16-68645369-T-C		EEM syndrome	Uncertain significance (Jan 13, 2018)
16-68645382-G-A		Retinitis pigmentosa	Likely pathogenic (Apr 01, 2018)
16-68645383-G-C		Inborn genetic diseases	Uncertain significance (Dec 21, 2023)
16-68645385-G-A			Likely benign (Jan 19, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CDH3	protein_coding	protein_coding	ENST00000264012	16	86428

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.80e-10	0.975	125697	0	51	125748	0.000203

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0798	468	473	0.990	0.0000293	5434
Missense in Polyphen		187	191.41	0.97698		2205
Synonymous	-0.828	217	202	1.07	0.0000141	1676
Loss of Function	2.24	21	35.4	0.593	0.00000185	412

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000239	0.000239
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000326	0.000326
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000202	0.000202
Middle Eastern	0.000326	0.000326
South Asian	0.000457	0.000457
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types.
• Disease: DISEASE: Hypotrichosis congenital with juvenile macular dystrophy (HJMD) [MIM:601553]: A disorder characterized by congenital hypotrichosis, early hair loss, and severe degenerative changes of the retinal macula that culminate in blindness during the second to third decade of life. {ECO:0000269|PubMed:11544476, ECO:0000269|PubMed:12445216}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Ectodermal dysplasia, ectrodactyly, and macular dystrophy syndrome (EEMS) [MIM:225280]: A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. It is an autosomal recessive condition characterized by features of ectodermal dysplasia such as sparse eyebrows and scalp hair, and selective tooth agenesis associated with macular dystrophy and ectrodactyly. {ECO:0000269|PubMed:15805154}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Cell adhesion molecules (CAMs) - Homo sapiens (human);Hair Follicle Development- Induction (Part 1 of 3);Overview of nanoparticle effects;EGFR1;Cell-cell junction organization;Adherens junctions interactions;Cell junction organization;Cell-Cell communication (Consensus)

Recessive Scores

• pRec: 0.0997

Intolerance Scores

• loftool: 0.729
• rvis_EVS: -0.1
• rvis_percentile_EVS: 45.66

Haploinsufficiency Scores

• pHI: 0.129
• hipred: N
• hipred_score: 0.489
• ghis: 0.466

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.788

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cdh3
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype

Gene ontology

• Biological process: cell morphogenesis;retina homeostasis;cell-cell junction assembly;cell adhesion;homophilic cell adhesion via plasma membrane adhesion molecules;visual perception;positive regulation of gene expression;positive regulation of keratinocyte proliferation;calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules;hair cycle process;keratinization;positive regulation of monophenol monooxygenase activity;negative regulation of transforming growth factor beta2 production;adherens junction organization;wound healing;response to drug;positive regulation of insulin-like growth factor receptor signaling pathway;cell-cell adhesion mediated by cadherin;positive regulation of melanin biosynthetic process;negative regulation of timing of catagen;regulation of hair cycle by canonical Wnt signaling pathway;positive regulation of canonical Wnt signaling pathway;cell-cell adhesion;positive regulation of melanosome transport
• Cellular component: cytoplasm;plasma membrane;cell-cell adherens junction;cell surface;integral component of membrane;catenin complex
• Molecular function: molecular_function;calcium ion binding;cytoskeletal protein binding;protein homodimerization activity;cadherin binding