CNPY3

protein-coding

canopy FGF signaling regulator 3

Gene summary

This gene encodes a protein that binds members of the toll-like receptor protein family and functions as a chaperone to aid in folding and export of these proteins. Alternative splicing results in multiple transcript variants. Naturally occuring readthrough transcription occurs between this locus and the downstream GNMT (glycine N-methyltransferase) gene and is represented with GeneID:107080644. [provided by RefSeq, Jan 2016]

Previous symbols:

TNRC5

MANE transcript

NM_006586.5

Inheritance

ClinVar variants

P:8U:60B:13

Top phenotype

Developmental and epileptic encephalopathy 60

gnomAD constraint

pLI —, LoF o/e 0.22

Max pathogenic AF

—

Genomic locus

chr6:42,929,480-42,939,294

External References & Databases

Ensembl (ENSG00000137161)

Transcript & Mutation Effects

hg38 • Region Span ~9.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

developmental and epileptic encephalopathy, 60LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0033369

Submitter: Ambry Genetics

developmental and epileptic encephalopathy, 60LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0033369

Submitter: Labcorp Genetics (formerly Invitae)

developmental and epileptic encephalopathy, 60STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0033369

Submitter: G2P

Clinical Genomic Database (CGD)

Developmental and epileptic encephalopathy 60AR

Manifestation: Neurologic

Intervention: General

Rationale: 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

Refs: 29394991

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CNPY3 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 54

Developmental and epileptic encephalopathy, 60Total: 21

not providedTotal: 19

CNPY3-related disorderTotal: 7

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006586.5. 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				10 clinvar		10
missense	1 clinvar		55 clinvar	3 clinvar		59
nonsense		2 clinvar	2 clinvar			4
start loss						0
frameshift	2 clinvar	1 clinvar				3
splice donor/acceptor (+/-2bp)	1 clinvar	1 clinvar	3 clinvar			5
Total	4	4	60	13	0	81

Highest pathogenic variant AF is 0.00000743605

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 55 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006586.5	RefSeq	NP_006577.2	6	MANE Select
ENST00000372836.5	Ensembl	ENSP00000361926.4	6	MANE Select
NM_001318842.1	RefSeq	NP_001305771.1	7	Standard
NM_001318845.1	RefSeq	NP_001305774.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Trafficking and processing of endosomal TLR
Toll-Like Receptors Cascades
Innate Immune System
Immune System

Biological Process

toll-like receptor signaling pathway
innate immune response

Molecular Function

signaling receptor binding

Cellular Component

endoplasmic reticulum lumen

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000372836
Coding exons: 6
Length: 10088
Individuals with no LoFs: 125743
Homozygous LoFs: 0
Heterozygous LoFs: 5
Defined: 125748
p: 0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.419	136	150	0.904	0.00000766	1795
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.115

Intolerance Scores

LoFtool: 0.335
RVIS EVS: 0.04
RVIS percentile EVS: 56.64

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.419

Gene Damage Prediction

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