CNPY3

Chr 6AR

canopy FGF signaling regulator 3

Also known as: CAG4A, DEE60, EIEE60, ERDA5, PRAT4A, TNRC5

NCBI Gene: 10695 ENSG00000137161 UniProt: Q9BT09 OMIM: 610774

The protein functions as a co-chaperone for HSP90B1 and is required for proper folding and endoplasmic reticulum export of most toll-like receptors, controlling both innate and adaptive immune responses. Biallelic mutations cause developmental and epileptic encephalopathy 60, inherited in an autosomal recessive pattern. This represents a neuroinflammatory condition affecting both developmental and epileptic manifestations in the pediatric population.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.571 OMIM phenotype

Clinical Summary— CNPY3

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.

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ClinVar Variants

8 unique Pathogenic / Likely Pathogenic· 58 VUS of 85 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.57LOEUF

pLI 0.398

Z-score 2.68

OE 0.22 (0.10–0.57)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.42Z-score

OE missense 0.90 (0.79–1.04)

136 obs / 150.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.22 (0.10–0.57)

0≤0.351.4

Missense OE?0.90 (0.79–1.04)

0≤0.61.4

Synonymous OE?0.81

0≤1.21.6

LoF obs/exp: 3 / 13.7Missense obs/exp: 136 / 150.5Syn Z: 1.18

ClinVar Variant Classifications

85 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4

Likely Pathogenic4

VUS58

Likely Benign9

Benign1

Conflicting1

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	3	1	0	0	4
Likely Pathogenic	4	0	0	0	4
VUS	3	54	1	0	58
Likely Benign	0	5	0	4	9
Benign	0	1	0	0	1
Conflicting	—				1
Total	10	61	1	4	77

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

8 pathogenic / likely-pathogenic (of 15) ClinVar copy-number / structural variants overlap CNPY3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →