CDH15

cadherin 15, the group of Type I classical cadherins

Basic information

Region (hg38): 16:89171747-89195492

Previous symbols: [ "CDH3", "CDH14" ]

Links

ENSG00000129910 ∙ NCBI:1013 ∙ OMIM:114019 ∙ HGNC:1754 ∙ Uniprot:P55291 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal dominant 3 (Limited), mode of inheritance: AD
• autosomal dominant non-syndromic intellectual disability (Supportive), mode of inheritance: AD
• intellectual disability, autosomal dominant 3 (Limited), mode of inheritance: AD
• intellectual disability, autosomal dominant 3 (Limited), mode of inheritance: AD
• intellectual disability (Disputed Evidence), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal dominant 3	AD	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	Craniofacial; Musculoskeletal; Neurologic	19012874

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CDH15 gene.

• not provided (109 variants)
• Inborn genetic diseases (66 variants)
• not specified (49 variants)
• Intellectual disability, autosomal dominant 3 (23 variants)
• CDH15-related condition (5 variants)
• Intellectual disability (1 variants)
• Intellectual disability, autosomal dominant 1 (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CDH15 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			2	34	9	45
missense			113	27	9	149
nonsense			1			1
start loss			1			1
frameshift			6			6
inframe indel			1	2		3
splice donor/acceptor (+/-2bp)			1			1
splice region			1	1	1	3
non coding			2	2		4
Total	0	0	127	65	18

Variants in CDH15

This is a list of pathogenic ClinVar variants found in the CDH15 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-89171833-T-A			Uncertain significance (Aug 17, 2017)
16-89171853-G-C		not specified	Uncertain significance (May 04, 2022)
16-89179418-C-G		not specified	Uncertain significance (Aug 30, 2022)
16-89179449-A-C			Likely benign (Nov 01, 2023)
16-89179450-G-A		not specified	Uncertain significance (Jun 09, 2022)
16-89179472-CT-C		not specified	Uncertain significance (May 04, 2022)
16-89179480-G-A		not specified • CDH15-related disorder	Conflicting classifications of pathogenicity (Mar 27, 2023)
16-89179482-G-T		not specified	Benign (Feb 27, 2019)
16-89179483-C-T		not specified	Uncertain significance (Oct 05, 2023)
16-89179484-G-A		CDH15-related disorder	Likely benign (Dec 01, 2023)
16-89179500-G-A		not specified	Uncertain significance (Oct 29, 2021)
16-89179500-G-T		not specified	Uncertain significance (Feb 27, 2023)
16-89179503-C-T		not specified	Uncertain significance (Sep 12, 2023)
16-89179504-G-A			Uncertain significance (-)
16-89179505-G-T			Likely benign (Apr 01, 2024)
16-89179525-C-T		not specified	Uncertain significance (May 08, 2023)
16-89179526-G-A		not specified	Benign (Jan 23, 2020)
16-89179533-G-A			Likely benign (Jan 01, 2024)
16-89179533-G-T		Intellectual disability, autosomal dominant 1	Uncertain significance (-)
16-89179538-C-T		not specified	Likely benign (Jan 09, 2020)
16-89179544-C-T		not specified	Likely benign (-)
16-89179547-C-T		not specified	Likely benign (-)
16-89179551-C-T		Intellectual disability, autosomal dominant 3	Likely benign (Jan 19, 2022)
16-89179552-G-A		not specified	Uncertain significance (Dec 19, 2022)
16-89179556-C-T		not specified	Likely benign (Sep 06, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CDH15	protein_coding	protein_coding	ENST00000289746	14	23726

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.77e-14	0.188	125485	0	179	125664	0.000712

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.01	591	526	1.12	0.0000342	5153
Missense in Polyphen		206	203.33	1.0131		2052
Synonymous	-2.20	294	250	1.18	0.0000179	1764
Loss of Function	1.09	25	31.6	0.791	0.00000150	321

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00344	0.00343
Ashkenazi Jewish	0.000101	0.0000993
East Asian	0.000785	0.000762
Finnish	0.0000472	0.0000462
European (Non-Finnish)	0.000316	0.000299
Middle Eastern	0.000785	0.000762
South Asian	0.000330	0.000327
Other	0.000658	0.000652

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. M-cadherin is part of the myogenic program and may provide a trigger for terminal muscle differentiation.
• Disease: DISEASE: Note=A chromosomal aberration involving CDH15 and KIRREL3 is found in a patient with severe mental retardation and dysmorphic facial features. Translocation t(11;16)(q24.2;q24).; DISEASE: Mental retardation, autosomal dominant 3 (MRD3) [MIM:612580]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. {ECO:0000269|PubMed:19012874}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• 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: 0.123

Intolerance Scores

• loftool: 0.663
• rvis_EVS: -1.08
• rvis_percentile_EVS: 7.28

Haploinsufficiency Scores

• pHI: 0.126
• hipred: N
• hipred_score: 0.486
• ghis: 0.614

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.830

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cdh15
• Phenotype: normal phenotype

Zebrafish Information Network

• Gene name: cdh15
• Affected structure: slow muscle cell
• Phenotype tag: abnormal
• Phenotype quality: elongated

Gene ontology

• Biological process: cell morphogenesis;cell-cell junction assembly;cell adhesion;homophilic cell adhesion via plasma membrane adhesion molecules;calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules;adherens junction organization;cell-cell adhesion mediated by cadherin;positive regulation of muscle cell differentiation;cell-cell adhesion
• Cellular component: Golgi apparatus;cytosol;plasma membrane;caveola;cell-cell adherens junction;cell surface;integral component of membrane;catenin complex;neuromuscular junction;extracellular exosome
• Molecular function: calcium ion binding;protein binding;cytoskeletal protein binding;protein homodimerization activity;cadherin binding