CELSR2

protein-coding

cadherin EGF LAG seven-pass G-type receptor 2, the group of CELSR cadherins|Adhesion G protein-coupled receptors, subfamily C

Gene summary

The protein encoded by this gene is a member of the flamingo subfamily, part of the cadherin superfamily. The flamingo subfamily consists of nonclassic-type cadherins; a subpopulation that does not interact with catenins. The flamingo cadherins are located at the plasma membrane and have nine cadherin domains, seven epidermal growth factor-like repeats and two laminin A G-type repeats in their ectodomain. They also have seven transmembrane domains, a characteristic unique to this subfamily. It is postulated that these proteins are receptors involved in contact-mediated communication, with cadherin domains acting as homophilic binding regions and the EGF-like domains involved in cell adhesion and receptor-ligand interactions. The specific function of this particular member has not been determined. [provided by RefSeq, Jul 2008]

Previous symbols:

EGFL2

MANE transcript

NM_001408.3

Inheritance

—

ClinVar variants

P:2U:547B:221

Top phenotype

CELSR2-related disorder

gnomAD constraint

pLI —, LoF o/e 0.17

Max pathogenic AF

—

Genomic locus

chr1:109,249,539-109,275,751

External References & Databases

Ensembl (ENSG00000143126)

Transcript & Mutation Effects

hg38 • Region Span ~26.2 kb

Loading mutation effect viewer...

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 CELSR2 variants in ClinVar

8 Conditions Cataloged

not specifiedTotal: 493

not providedTotal: 354

CELSR2-related disorderTotal: 53

Idiopathic scoliosisTotal: 1

Orofacial-digital syndrome IIITotal: 1

Esophageal atresia/tracheoesophageal fistulaTotal: 1

Global developmental delayTotal: 1

Intellectual disabilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001408.3. 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	151 clinvar	22 clinvar	176
missense		2 clinvar	534 clinvar	33 clinvar	15 clinvar	584
nonsense			3 clinvar			3
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	2	547	184	37	770

Highest pathogenic variant AF is 0.000040955376

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001408.3	RefSeq	NP_001399.1	34	MANE Select
ENST00000271332.4	Ensembl	ENSP00000271332.3	34	MANE Select

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
celsr2	Danio rerio	Structure: facial nerve motor nucleus Quality: mislocalised abnormal

Gene / Model

Organism

Observed Phenotype

celsr2

Danio rerio

Structure: facial nerve motor nucleus

Quality: mislocalised

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

GPCRs, Other
Ectoderm Differentiation

Biological Process

regulation of transcription, DNA-templated
homophilic cell adhesion via plasma membrane adhesion molecules
G protein-coupled receptor signaling pathway
Wnt signaling pathway
neural plate anterior/posterior regionalization

Molecular Function

G protein-coupled receptor activity
calcium ion binding

Cellular Component

cytoplasm
plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000271332
Coding exons: 34
Length: 25732
Individuals with no LoFs: 125719
Homozygous LoFs: 0
Heterozygous LoFs: 29
Defined: 125748
p: 0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.18	1555	1.82e+3	0.856	0.000121	18738
Missense (PolyPhen)		505	711.23	0.71004		7405
Synonymous	-1.74	847	785	1.08	0.0000533	6273
Loss of Function	8.24	20	116	0.173	0.00000676	1168

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000092	0.000087	rare
Ashkenazi Jewish	0.00011	0.000099	rare
East Asian	0.000054	0.000054	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00016	0.00016	rare
South Asian	0.000067	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Receptor that may have an important role in cell/cell signaling during nervous system formation.;

Recessive Scores

pRec: 0.150

Intolerance Scores

LoFtool: 0.228
RVIS EVS: -1.81
RVIS percentile EVS: 2.18

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.605

Gene Damage Prediction

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