CDH12

protein-coding

cadherin 12, the group of Type II classical cadherins

Gene summary

This gene encodes a type II classical cadherin of the cadherin superfamily. Alternative splicing of this gene results in multiple transcript variants. At least one of these variants encodes a preproprotein that is proteolytically processed to generate the mature cadherin protein. These integral membrane proteins mediate calcium-dependent cell-cell adhesion and are composed of a large N-terminal extracellular domain, a single membrane-spanning domain, and a small, highly conserved C-terminal cytoplasmic domain. Type II (atypical) cadherins are defined based on their lack of a histidine-alanine-valine (HAV) cell adhesion recognition sequence specific to type I cadherins. This particular cadherin appears to be expressed specifically in the brain and its temporal pattern of expression would be consistent with a role during a critical period of neuronal development, perhaps specifically during synaptogenesis. [provided by RefSeq, Nov 2015]

MANE transcript

NM_004061.5

Inheritance

—

ClinVar variants

U:116B:22

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.36

Max pathogenic AF

—

Genomic locus

chr5:21,750,673-22,853,344

External References & Databases

Ensembl (ENSG00000154162)

Transcript & Mutation Effects

hg38 • Region Span ~1,102.7 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 CDH12 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 108

not providedTotal: 23

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004061.5. 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			2 clinvar	10 clinvar	6 clinvar	18
missense			112 clinvar	3 clinvar	3 clinvar	118
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	116	13	9	138

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004061.5	RefSeq	NP_004052.2	11	MANE Select
ENST00000382254.6	Ensembl	ENSP00000371689.1	11	MANE Select
NM_001317227.2	RefSeq	NP_001304156.1	11	Standard
NM_001317228.1	RefSeq	NP_001304157.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cell-cell junction organization
Adherens junctions interactions
Cell junction organization
Cell-Cell communication

Biological Process

cell morphogenesis
cell-cell junction assembly
homophilic cell adhesion via plasma membrane adhesion molecules
calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules
adherens junction organization

Molecular Function

calcium ion binding
cytoskeletal protein binding
protein homodimerization activity
cadherin binding

Cellular Component

plasma membrane
cell-cell adherens junction
cell surface
integral component of membrane
catenin complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000382254
Coding exons: 11
Length: 1102950
Individuals with no LoFs: 125720
Homozygous LoFs: 0
Heterozygous LoFs: 26
Defined: 125746
p: 0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.931	393	449	0.876	0.0000240	5203
Missense (PolyPhen)		132	189.49	0.6966		2288
Synonymous	-0.944	186	170	1.09	0.0000101	1562
Loss of Function	3.42	12	33.3	0.360	0.00000176	400

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00023	0.00022	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.000089	0.000088	rare
South Asian	0.00013	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.126

Intolerance Scores

LoFtool: 0.638
RVIS EVS: -0.35
RVIS percentile EVS: 29.49

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.293

Gene Damage Prediction

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