CDH15

cadherin 15, the group of Type I classical cadherins

Basic information

Region (hg38): 16:89171748-89195492

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 (Disputed Evidence), mode of inheritance: AD
intellectual disability, autosomal dominant 3 (Limited), 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_specified (212 variants)
not_provided (125 variants)
Intellectual_disability,_autosomal_dominant_3 (30 variants)
CDH15-related_disorder (24 variants)
Intellectual_disability (8 variants)
von_Willebrand_disease_type_1 (1 variants)
Neurofibromatosis,_type_1 (1 variants)
See_cases (1 variants)
Intellectual_disability,_autosomal_dominant_1 (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. These statistics are base on transcript: NM_000004933.3. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	51 clinvar	5 clinvar	59
missense			210 clinvar	45 clinvar	5 clinvar	260
nonsense			3 clinvar			3
start loss			1			1
frameshift			7 clinvar			7
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	225	96	10

Loading clinvar variants...

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