CELSR3
protein-codingcadherin EGF LAG seven-pass G-type receptor 3, the group of Adhesion G protein-coupled receptors, subfamily C|MicroRNA protein coding host genes|CELSR cadherins
Gene summary
This gene belongs to the flamingo subfamily, which is included in the cadherin superfamily. The flamingo cadherins consist of nonclassic-type cadherins that do not interact with catenins. They are plasma membrane proteins containing seven epidermal growth factor-like repeats, nine cadherin domains and two laminin A G-type repeats in their ectodomain. They also have seven transmembrane domains, a characteristic feature of their subfamily. The encoded protein may be involved in the regulation of contact-dependent neurite growth and may play a role in tumor formation. [provided by RefSeq, Jun 2013]
- EGFL1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~26.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0100038
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0100038
Submitter: LiferaOmics
Genetic evidence – Published: PMID: 38429302 — 11 independent families / 12 affected individuals with bi-allelic CELSR3 variants and an overlapping spectrum of CNS anomalies (with or without additional congenital anomalies of the kidneys/urinary tract); AR inheritance; segregation details variably reported across families; no case-control data. Because the majority of reported alleles are non-pLoF (predominantly missense / in-frame), case-level points were assigned using the AR “other variant” default of 0.1 per proband, total 1.2 points (12 probands × 0.1). Segregation = 1 (not consistently extractable/counted here); case-control = 0. Published genetic evidence total = 2.2 / 12 Genetic evidence – Our case: 1 proband (4-year-old female) with global developmental delay, severe growth faltering, tone abnormality (hypotonia → hypertonia), and multiple congenital anomalies (cataracts, hydrocephalus, VSD, talipes equinovarus); positive consanguinity; prior similarly affected pregnancy terminated for antenatal hydrocephalus/VSD/talipes (not genotyped); ES identified homozygous nonsense CELSR3 NM_001407.2:c.652G>T; p.(Glu218Ter) (predicted null); AR inheritance; no genotyped additional affected relatives; no segregation or case-control data. Case-level points (default for predicted null in AR disease) = 1.0 (AR predicted/proven null = 1.5, −0.5 downgrade for homozygosity/consanguinity); segregation = 0; case-control = 0. Our case contribution = 1.0 / 12 Total genetic evidence (published + current) = 3.2 / 12 Experimental evidence – Published: PMID: 38429302 — Protein structural modeling of variants (supportive), CELSR3 immunolocalization in human embryonic urinary tract, and zebrafish transient suppression with rescue experiments supporting an embryonic role for CELSR3 in CNS/urinary tract formation. Points = 3.0 (expression/localization = 1.5; in vivo model + rescue = 2.5). Experimental evidence total = 4.0 / 6 Overall score = 7.2
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CELSR3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001407.3. 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 | 65 | 4 | 72 | ||
| missense | 14 | 421 | 39 | 13 | 487 | |
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 1 | 4 | |||
| Total | 0 | 14 | 428 | 105 | 17 | 564 |
Highest pathogenic variant AF is 0.00013876671
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001398.2 | 35 | MANE Select | |
| Ensembl | ENSP00000164024.4 | 35 | MANE Select |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| celsr3 | Danio rerio | Structure: ON-bipolar cell Quality: functionality abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- GPCRs, Other
Biological Process
- neuron migration
- regulation of protein phosphorylation
- homophilic cell adhesion via plasma membrane adhesion molecules
- G protein-coupled receptor signaling pathway
- axonal fasciculation
Molecular Function
- G protein-coupled receptor activity
- calcium ion binding
- protein binding
Cellular Component
- plasma membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000164024
- Coding exons
- 35
- Length
- 26447
- Individuals with no LoFs
- 125676
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 71
- Defined
- 125748
- p
- 0.000286
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 4.08 | 1554 | 2.08e+3 | 0.748 | 0.000135 | 21145 |
| Missense (PolyPhen) | 530 | 903.29 | 0.58674 | 9468 | ||
| Synonymous | 2.01 | 810 | 886 | 0.914 | 0.0000573 | 7324 |
| Loss of Function | 8.54 | 21 | 123 | 0.170 | 0.00000693 | 1231 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.0020 | 0.0011 | notable |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.00024 | 0.00023 | rare |
| European (Non-Finnish) | 0.00012 | 0.00011 | rare |
| South Asian | 0.00046 | 0.00036 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Receptor that may have an important role in cell/cell signaling during nervous system formation.;
Recessive Scores
- pRec
- 0.245
Intolerance Scores
- LoFtool
- 0.385
- RVIS EVS
- -4.27
- RVIS percentile EVS
- 0.11
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.844
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |