CDH4

cadherin 4, the group of Type I classical cadherins

Basic information

Region (hg38): 20:61252260-61940617

Links

ENSG00000179242 ∙ NCBI:1002 ∙ OMIM:603006 ∙ HGNC:1763 ∙ Uniprot:P55283 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• multiple congenital anomalies/dysmorphic syndrome (Limited), mode of inheritance: AR

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CDH4 gene.

• Inborn genetic diseases (50 variants)
• not provided (14 variants)
• CDH4-related condition (3 variants)
• Simplified gyral pattern (2 variants)
• Abnormal brain morphology (1 variants)
• CDH4-associated disorder of corticaldevelopment (1 variants)
• Neurodevelopmental disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CDH4 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	3	9
missense		1	54	3	1	59
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1		2	3
non coding			1			1
Total	0	1	55	9	4

Variants in CDH4

This is a list of pathogenic ClinVar variants found in the CDH4 region.

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

Position	Type	Phenotype	Significance	ClinVar
20-61252574-A-G			Uncertain significance (Apr 01, 2022)
20-61254837-G-T		not specified	Uncertain significance (Nov 22, 2022)
20-61254845-C-T		not specified	Uncertain significance (Jul 09, 2021)
20-61254848-C-T			Likely benign (Nov 19, 2018)
20-61254857-C-A		not specified	Uncertain significance (Feb 17, 2023)
20-61254865-G-A			Benign (Dec 31, 2019)
20-61254884-A-G		not specified	Uncertain significance (Oct 03, 2022)
20-61254890-C-T		not specified	Uncertain significance (Mar 29, 2022)
20-61489557-C-T		CDH4-associated disorder of corticaldevelopment	Uncertain significance (Aug 06, 2021)
20-61499482-C-T		CDH4-related disorder	Likely benign (Mar 21, 2019)
20-61499489-G-T		CDH4-related disorder	Likely benign (Jun 05, 2023)
20-61743678-C-T		CDH4-related disorder	Likely benign (Sep 05, 2019)
20-61743724-G-A		not specified	Uncertain significance (Nov 17, 2022)
20-61743736-G-A		not specified	Uncertain significance (Dec 08, 2023)
20-61743739-G-A		not specified	Likely benign (May 15, 2023)
20-61743746-G-A		not specified	Uncertain significance (Sep 21, 2023)
20-61743769-T-A		not specified	Uncertain significance (Oct 27, 2023)
20-61773022-T-A		not specified	Uncertain significance (Dec 19, 2023)
20-61773025-T-G		not specified	Uncertain significance (Jul 25, 2023)
20-61773036-C-G		not specified	Uncertain significance (Jul 20, 2021)
20-61773058-C-T		not specified	Uncertain significance (Sep 27, 2022)
20-61773073-C-G		Inborn genetic diseases	Uncertain significance (Nov 15, 2021)
20-61852801-C-T			Likely benign (Sep 13, 2018)
20-61852820-G-A		not specified	Uncertain significance (Jun 29, 2023)
20-61852870-C-T			Benign (Dec 31, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CDH4	protein_coding	protein_coding	ENST00000360469	16	688192

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.743	0.257	125736	0	12	125748	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.02	480	622	0.772	0.0000438	5987
Missense in Polyphen		131	229.5	0.5708		2138
Synonymous	-0.879	295	276	1.07	0.0000230	1854
Loss of Function	4.66	8	39.7	0.202	0.00000214	410

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.0000994	0.0000992
East Asian	0.000164	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000354	0.0000352
Middle Eastern	0.000164	0.000163
South Asian	0.0000989	0.0000980
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. May play an important role in retinal development.
• Pathway: Cell adhesion molecules (CAMs) - Homo sapiens (human);Developmental Biology;CDO in myogenesis;Myogenesis;Cell-cell junction organization;Adherens junctions interactions;Cell junction organization;Cell-Cell communication (Consensus)

Recessive Scores

• pRec: 0.143

Intolerance Scores

• loftool: 0.252
• rvis_EVS: -2.07
• rvis_percentile_EVS: 1.62

Haploinsufficiency Scores

• pHI: 0.141
• hipred: Y
• hipred_score: 0.625
• ghis: 0.635

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.803

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cdh4
• Phenotype: cellular phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; renal/urinary system phenotype

Zebrafish Information Network

• Gene name: cdh4
• Affected structure: retinal ganglion cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: cell morphogenesis;cell-cell junction assembly;cell adhesion;homophilic cell adhesion via plasma membrane adhesion molecules;heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules;axon guidance;calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules;adherens junction organization;cell-cell adhesion mediated by cadherin;positive regulation of axon extension;cell-cell adhesion
• Cellular component: plasma membrane;integral component of plasma membrane;cell-cell adherens junction;cell surface;catenin complex
• Molecular function: calcium ion binding;cytoskeletal protein binding;protein homodimerization activity;cadherin binding