CDHR1

cadherin related family member 1, the group of Cadherin related

Basic information

Region (hg38): 10:84194536-84219621

Previous symbols: [ "PCDH21" ]

Links

ENSG00000148600 ∙ NCBI:92211 ∙ OMIM:609502 ∙ HGNC:14550 ∙ Uniprot:Q96JP9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• retinitis pigmentosa (Supportive), mode of inheritance: AD
• cone-rod dystrophy (Supportive), mode of inheritance: AD
• cone-rod dystrophy 15 (Strong), mode of inheritance: AR
• cone-rod dystrophy 15 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cone-rod dystrophy 15; Retinitis pigmentosa 65	AR	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	Ophthalmologic	20805371

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CDHR1 gene.

• not provided (703 variants)
• Cone-rod dystrophy 15 (159 variants)
• Inborn genetic diseases (45 variants)
• Cone-Rod Dystrophy, Recessive (42 variants)
• not specified (22 variants)
• Retinal dystrophy (15 variants)
• Retinitis pigmentosa (9 variants)
• Retinitis pigmentosa 65 (4 variants)
• Macular dystrophy, retinal, 5 (3 variants)
• CDHR1-related condition (2 variants)
• Cone-rod dystrophy (2 variants)
• Cone dystrophy (1 variants)
• Leber congenital amaurosis (1 variants)
• maculopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CDHR1 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			7	129	5	141
missense	1	1	318	21	2	343
nonsense	13	2	2			17
start loss						0
frameshift	29	7	3			39
inframe indel			9	1		10
splice donor/acceptor (+/-2bp)	5	13	2			20
splice region			20	23	1	44
non coding			69	74	22	165
Total	48	23	410	225	29

Highest pathogenic variant AF is 0.000341

Variants in CDHR1

This is a list of pathogenic ClinVar variants found in the CDHR1 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-84194697-G-A		Cone-rod dystrophy 15	Likely benign (Jan 13, 2018)
10-84194728-C-T		Cone-rod dystrophy 15	Uncertain significance (Jan 13, 2018)
10-84194760-C-T		not specified • Cone-rod dystrophy 15	Benign/Likely benign (Jan 13, 2018)
10-84194761-A-G		Cone-rod dystrophy 15 • Retinitis pigmentosa	Conflicting classifications of pathogenicity (Sep 05, 2023)
10-84194761-A-T		Retinitis pigmentosa	Pathogenic (Jun 23, 2019)
10-84194764-A-G			Uncertain significance (May 08, 2023)
10-84194767-C-T			Uncertain significance (Sep 19, 2022)
10-84194769-CT-C		Cone-rod dystrophy 15	Likely pathogenic (Jan 25, 2023)
10-84194773-C-T			Uncertain significance (Jul 05, 2022)
10-84194777-G-A			Pathogenic (Jun 06, 2023)
10-84194778-G-A			Pathogenic (Nov 02, 2021)
10-84194781-C-T			Likely benign (Jun 17, 2022)
10-84194784-C-T			Likely benign (May 18, 2022)
10-84194789-C-T			Uncertain significance (Aug 31, 2022)
10-84194790-C-A		CDHR1-related disorder	Likely benign (Sep 01, 2023)
10-84194799-G-A			Likely benign (Sep 22, 2022)
10-84194800-C-G			Uncertain significance (Feb 02, 2022)
10-84194804-G-T		Cone-rod dystrophy 15 • CDHR1-related disorder	Conflicting classifications of pathogenicity (Nov 20, 2023)
10-84194808-C-G			Likely benign (Dec 11, 2023)
10-84194810-G-A			Uncertain significance (Mar 23, 2023)
10-84194812-TT-GC			Uncertain significance (Feb 08, 2022)
10-84194816-G-A		Retinal dystrophy • CDHR1-related disorder	Likely pathogenic (Dec 04, 2023)
10-84194820-G-A			Uncertain significance (Nov 22, 2022)
10-84194821-T-C			Uncertain significance (Aug 31, 2022)
10-84194824-C-A			Likely benign (Oct 10, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CDHR1	protein_coding	protein_coding	ENST00000372117	17	24968

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.84e-21	0.00199	125652	0	96	125748	0.000382

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.697	534	491	1.09	0.0000305	5605
Missense in Polyphen		165	155.58	1.0606		1777
Synonymous	-0.229	210	206	1.02	0.0000145	1769
Loss of Function	0.126	32	32.8	0.976	0.00000160	392

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00118	0.00117
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000318	0.000316
Middle Eastern	0.000109	0.000109
South Asian	0.000687	0.000686
Other	0.000815	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Potential calcium-dependent cell-adhesion protein. May be required for the structural integrity of the outer segment (OS) of photoreceptor cells (By similarity). {ECO:0000250}.
• Disease: DISEASE: Cone-rod dystrophy 15 (CORD15) [MIM:613660]: An inherited retinal dystrophy characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa, due to cone photoreceptors degenerating at a higher rate than rod photoreceptors. {ECO:0000269|PubMed:20805371, ECO:0000269|PubMed:26350383}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.144

Intolerance Scores

• loftool: 0.893
• rvis_EVS: 0.01
• rvis_percentile_EVS: 54.18

Haploinsufficiency Scores

• pHI: 0.443
• hipred: N
• hipred_score: 0.342
• ghis: 0.494

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.539

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cdhr1
• Phenotype: vision/eye phenotype; normal phenotype

Gene ontology

• Biological process: cell adhesion;homophilic cell adhesion via plasma membrane adhesion molecules;photoreceptor cell morphogenesis;photoreceptor cell outer segment organization;photoreceptor cell maintenance
• Cellular component: cellular_component;integral component of plasma membrane;photoreceptor outer segment membrane
• Molecular function: molecular_function;calcium ion binding