CDHR2

protein-coding

cadherin related family member 2, the group of Cadherin related

Gene summary

This gene is a member of the protocadherin family, which represents a subset of the larger cadherin superfamily. The members of the protocadherin family encode non-classical cadherins that function as calcium-dependent cell-cell adhesion molecules. This protocadherin represents a new candidate for tumor suppression. Alternatively spliced transcript variants that encode the same protein have been identified. [provided by RefSeq, Jan 2010]

Previous symbols:

PCDH24

MANE transcript

NM_017675.6

Inheritance

—

ClinVar variants

U:239B:25

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.65

Max pathogenic AF

—

Genomic locus

chr5:176,542,511-176,595,974

External References & Databases

Ensembl (ENSG00000074276)

Transcript & Mutation Effects

hg38 • Region Span ~53.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CDHR2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 243

not providedTotal: 10

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017675.6. 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			3 clinvar	8 clinvar		11
missense			232 clinvar	17 clinvar		249
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	239	25	0	264

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 29 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017675.6	RefSeq	NP_060145.3	31	MANE Select
ENST00000261944.10	Ensembl	ENSP00000261944.5	31	MANE Select
NM_001171976.2	RefSeq	NP_001165447.1	31	Standard
ENST00000510124.5	Ensembl	ENSP00000426838.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

homophilic cell adhesion via plasma membrane adhesion molecules
epithelial cell differentiation
regulation of microvillus length
cell-cell adhesion mediated by cadherin
negative regulation of cell growth involved in contact inhibition

Molecular Function

calcium ion binding
protein binding
cell adhesion molecule binding

Cellular Component

brush border
apical plasma membrane
cell junction
brush border membrane
microvillus membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000510636
Coding exons: 31
Length: 53464
Individuals with no LoFs: 125556
Homozygous LoFs: 0
Heterozygous LoFs: 192
Defined: 125748
p: 0.000764

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.372	767	797	0.963	0.0000490	8519
Missense (PolyPhen)		218	241.71	0.90192		2772
Synonymous	-0.913	393	371	1.06	0.0000268	2707
Loss of Function	2.53	41	62.6	0.655	0.00000326	663

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0017	0.0017	notable
Latino/Admixed American	0.00073	0.00064	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.0010	0.0010	notable
Finnish	0.00032	0.00032	rare
European (Non-Finnish)	0.00083	0.00082	rare
South Asian	0.00062	0.00056	rare
Other	0.00065	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Intermicrovillar adhesion molecule that forms, via its extracellular domain, calcium-dependent heterophilic complexes with CDHR5 on adjacent microvilli. Thereby, controls the packing of microvilli at the apical membrane of epithelial cells. Through its cytoplasmic domain, interacts with microvillus cytoplasmic proteins to form the intermicrovillar adhesion complex/IMAC. This complex plays a central role in microvilli and epithelial brush border differentiation (PubMed:24725409). May also play a role in cell-cell adhesion and contact inhibition in epithelial cells (PubMed:12117771). {ECO:0000269|PubMed:12117771, ECO:0000269|PubMed:24725409}.;

Recessive Scores

pRec: 0.0898

Intolerance Scores

LoFtool: 0.799
RVIS EVS: 0.96
RVIS percentile EVS: 90.12

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

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