CELSR1

cadherin EGF LAG seven-pass G-type receptor 1, the group of Adhesion G protein-coupled receptors, subfamily C|CELSR cadherins

Basic information

Region (hg38): 22:46360833-46537620

Links

ENSG00000075275 ∙ NCBI:9620 ∙ OMIM:604523 ∙ HGNC:1850 ∙ Uniprot:Q9NYQ6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neural tube defects, susceptibility to (Moderate), mode of inheritance: AD
• neural tube defects, susceptibility to (Limited), mode of inheritance: AD
• lymphatic malformation 9 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Lymphatic malformation 9	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	Cardiovascular	26855770; 31215153; 31403174

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CELSR1 gene.

• not provided (170 variants)
• Inborn genetic diseases (169 variants)
• Lymphatic malformation 9 (11 variants)
• CELSR1-related condition (8 variants)
• Lymphatic malformation (5 variants)
• Walker-Warburg congenital muscular dystrophy (2 variants)
• CELSR1-associated congenital heartdefects (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CELSR1 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	26	39	67
missense			216	26	18	260
nonsense		1	3			4
start loss						0
frameshift		1	3	1	1	6
inframe indel			2		1	3
splice donor/acceptor (+/-2bp)	2	1	1			4
splice region			1	4	1	6
non coding					4	4
Total	2	3	227	53	63

Variants in CELSR1

This is a list of pathogenic ClinVar variants found in the CELSR1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
22-46363187-CCTGATGGTTCAAATTGAAGTTTCATTA-C			Benign (Dec 31, 2019)
22-46364011-T-G		not specified	Uncertain significance (Sep 29, 2022)
22-46364022-G-T		not specified	Uncertain significance (Nov 15, 2021)
22-46364032-C-T		not specified	Uncertain significance (May 04, 2022)
22-46364041-A-G		not specified	Uncertain significance (Dec 19, 2022)
22-46364043-G-C		CELSR1-related disorder	Benign (Jan 02, 2020)
22-46364052-G-A		CELSR1-related disorder	Likely benign (Nov 21, 2019)
22-46364070-C-T		CELSR1-related disorder	Benign (Feb 26, 2020)
22-46364084-G-C		CELSR1-related disorder	Benign (Dec 31, 2019)
22-46364131-G-A		not specified	Uncertain significance (Jul 26, 2021)
22-46364133-CGTGCGCGAGGAT-C		CELSR1-related disorder	Benign (Sep 26, 2019)
22-46364139-C-T		CELSR1-related disorder	Likely benign (Apr 22, 2022)
22-46364140-G-A		CELSR1-related disorder	Benign (Feb 21, 2020)
22-46364168-C-T		not specified	Uncertain significance (Feb 13, 2024)
22-46364179-C-T		not specified	Uncertain significance (Oct 05, 2022)
22-46364180-G-A		not specified	Uncertain significance (Jul 21, 2021)
22-46364186-G-A		not specified	Uncertain significance (Aug 17, 2021)
22-46364189-C-T		CELSR1-related disorder	Benign (Oct 29, 2019)
22-46364197-G-A		not specified	Uncertain significance (Dec 12, 2023)
22-46364205-C-T		CELSR1-related disorder	Benign (Feb 21, 2020)
22-46364206-G-A		not specified	Uncertain significance (Jan 31, 2023)
22-46364218-G-T		not specified	Conflicting classifications of pathogenicity (Oct 01, 2022)
22-46364224-G-A			Uncertain significance (Aug 02, 2018)
22-46364571-T-TC			Uncertain significance (Jan 17, 2020)
22-46364573-C-T			Likely benign (Apr 01, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CELSR1	protein_coding	protein_coding	ENST00000262738	35	176337

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000598	121369	365	4014	125748	0.0176

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.20	1731	1.88e+3	0.922	0.000136	19376
Missense in Polyphen		700	907.13	0.77166		8887
Synonymous	-3.54	1003	870	1.15	0.0000735	6342
Loss of Function	7.97	18	107	0.168	0.00000558	1149

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.228	0.224
Ashkenazi Jewish	0.00438	0.00428
East Asian	0.000329	0.000326
Finnish	0.00413	0.00231
European (Non-Finnish)	0.0104	0.00590
Middle Eastern	0.000329	0.000326
South Asian	0.00359	0.00193
Other	0.0121	0.0101

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor that may have an important role in cell/cell signaling during nervous system formation.
• Disease: DISEASE: Neural tube defects (NTD) [MIM:182940]: Congenital malformations of the central nervous system and adjacent structures related to defective neural tube closure during the first trimester of pregnancy. Failure of neural tube closure can occur at any level of the embryonic axis. Common NTD forms include anencephaly, myelomeningocele and spina bifida, which result from the failure of fusion in the cranial and spinal region of the neural tube. NTDs have a multifactorial etiology encompassing both genetic and environmental components. {ECO:0000269|PubMed:22095531}. Note=The disease may be caused by mutations affecting the gene represented in this entry.
• Pathway: GPCRs, Other (Consensus)

Recessive Scores

• pRec: 0.148

Intolerance Scores

• loftool: 0.157
• rvis_EVS: -2.82
• rvis_percentile_EVS: 0.63

Haploinsufficiency Scores

• pHI: 0.504
• hipred: Y
• hipred_score: 0.639
• ghis: 0.494

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.804

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Celsr1
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; cellular phenotype; vision/eye phenotype; craniofacial phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; immune system phenotype; skeleton phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype

Gene ontology

• Biological process: establishment of planar polarity;neuron migration;neural tube closure;hair follicle development;homophilic cell adhesion via plasma membrane adhesion molecules;G protein-coupled receptor signaling pathway;Rho protein signal transduction;central nervous system development;locomotory behavior;anterior/posterior pattern specification;regulation of actin cytoskeleton organization;wound healing;establishment of planar polarity of embryonic epithelium;inner ear morphogenesis;apical protein localization;establishment of body hair planar orientation;Wnt signaling pathway, planar cell polarity pathway;orthogonal dichotomous subdivision of terminal units involved in lung branching morphogenesis;planar dichotomous subdivision of terminal units involved in lung branching morphogenesis;lateral sprouting involved in lung morphogenesis;planar cell polarity pathway involved in neural tube closure;protein localization involved in establishment of planar polarity
• Cellular component: nucleoplasm;plasma membrane;integral component of plasma membrane;integral component of membrane
• Molecular function: transmembrane signaling receptor activity;G protein-coupled receptor activity;calcium ion binding;protein dimerization activity