CNPY3

canopy FGF signaling regulator 3

Basic information

Region (hg38): 6:42929479-42939294

Previous symbols: [ "TNRC5" ]

Links

ENSG00000137161 ∙ NCBI:10695 ∙ OMIM:610774 ∙ HGNC:11968 ∙ Uniprot:Q9BT09 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• developmental and epileptic encephalopathy, 60 (Limited), mode of inheritance: AR
• West syndrome (Supportive), mode of inheritance: AD
• developmental and epileptic encephalopathy, 60 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental and epileptic encephalopathy 60	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	Neurologic	29394991

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CNPY3 gene.

• Developmental and epileptic encephalopathy, 60 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CNPY3 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				4		4
missense			17	1		18
nonsense		1				1
start loss						0
frameshift	1	1				2
inframe indel				1	1	2
splice donor/acceptor (+/-2bp)		1	1			2
splice region						0
non coding			1			1
Total	1	3	19	6	1

Variants in CNPY3

This is a list of pathogenic ClinVar variants found in the CNPY3 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-42929592-G-C		not specified	Uncertain significance (Jan 03, 2024)
6-42929619-TTGC-T		CNPY3-related disorder	Benign (Oct 25, 2023)
6-42929619-TTGCTGCTGCTGC-T		Developmental and epileptic encephalopathy, 60	Conflicting classifications of pathogenicity (Jan 01, 2024)
6-42929619-T-TTGC		CNPY3-related disorder	Likely benign (Dec 13, 2022)
6-42929619-T-TTGCTGC		not specified	Uncertain significance (Apr 01, 2024)
6-42929619-T-TTGCTGCTGCTGCTGC		Developmental and epileptic encephalopathy, 60	Uncertain significance (Jul 08, 2024)
6-42929626-T-C		not specified	Uncertain significance (Aug 28, 2023)
6-42929631-C-T			Likely benign (Sep 01, 2020)
6-42929638-T-C		not specified	Uncertain significance (Dec 06, 2022)
6-42929644-T-C		not specified	Uncertain significance (May 25, 2022)
6-42929649-G-A		not specified	Uncertain significance (May 21, 2024)
6-42929685-G-A		not specified	Uncertain significance (May 01, 2024)
6-42934522-G-A		Developmental and epileptic encephalopathy, 60 • not specified	Uncertain significance (Mar 02, 2023)
6-42934564-G-T		Developmental and epileptic encephalopathy, 60	Uncertain significance (Aug 30, 2023)
6-42934566-C-G			Uncertain significance (Sep 01, 2020)
6-42934599-G-A		Developmental and epileptic encephalopathy, 60	Uncertain significance (Jan 31, 2019)
6-42935542-G-A		Developmental and epileptic encephalopathy, 60	Uncertain significance (May 13, 2020)
6-42935590-G-A		not specified	Uncertain significance (Dec 14, 2023)
6-42935645-G-C		not specified	Uncertain significance (Mar 21, 2023)
6-42935650-G-A		not specified	Uncertain significance (Nov 10, 2022)
6-42935660-G-A		Developmental and epileptic encephalopathy, 60	Uncertain significance (Feb 14, 2020)
6-42937717-G-C		Developmental and epileptic encephalopathy, 60	Pathogenic (Nov 17, 2020)
6-42937840-G-A		Developmental and epileptic encephalopathy, 60	Pathogenic (Nov 17, 2020)
6-42938085-AAC-A		Developmental and epileptic encephalopathy, 60 • not specified	Likely pathogenic (Jan 18, 2024)
6-42938126-G-C		not specified	Uncertain significance (Mar 30, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CNPY3	protein_coding	protein_coding	ENST00000372836	6	10088

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.398	0.601	125743	0	5	125748	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.419	136	150	0.904	0.00000766	1795
Missense in Polyphen		43	57.504	0.74778		682
Synonymous	1.18	54	66.3	0.815	0.00000385	539
Loss of Function	2.67	3	13.7	0.219	7.41e-7	162

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000904	0.0000904
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.00000879	0.00000879
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Toll-like receptor (TLR)-specific co-chaperone for HSP90B1. Required for proper TLR folding, except that of TLR3, and hence controls TLR exit from the endoplasmic reticulum. Consequently, required for both innate and adaptive immune responses (By similarity). {ECO:0000250}.
• Disease: DISEASE: Epileptic encephalopathy, early infantile, 60 (EIEE60) [MIM:617929]: A form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. EIEE60 is an autosomal recessive condition characterized by onset of seizures in the first months of life. {ECO:0000269|PubMed:29394991}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Trafficking and processing of endosomal TLR;Toll-Like Receptors Cascades;Innate Immune System;Immune System (Consensus)

Recessive Scores

• pRec: 0.115

Intolerance Scores

• loftool: 0.335
• rvis_EVS: 0.04
• rvis_percentile_EVS: 56.64

Haploinsufficiency Scores

• pHI: 0.0707
• hipred: Y
• hipred_score: 0.518
• ghis: 0.611

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.419

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cnpy3
• Phenotype: hematopoietic system 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); immune system phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: toll-like receptor signaling pathway;innate immune response
• Cellular component: endoplasmic reticulum lumen
• Molecular function: signaling receptor binding