CPNE1

protein-coding

copine 1, the group of Copines

Gene summary

Calcium-dependent membrane-binding proteins may regulate molecular events at the interface of the cell membrane and cytoplasm. This gene encodes a calcium-dependent protein that also contains two N-terminal type II C2 domains and an integrin A domain-like sequence in the C-terminus. However, the encoded protein does not contain a predicted signal sequence or transmembrane domains. This protein has a broad tissue distribution and it may function in membrane trafficking. This gene and the gene for RNA binding motif protein 12 overlap at map location 20q11.21. Alternate splicing results in multiple transcript variants encoding different proteins. [provided by RefSeq, Aug 2008]

MANE transcript

NM_152925.3

Inheritance

—

ClinVar variants

U:94B:6

Top phenotype

RBM12-related disorder

gnomAD constraint

pLI —, LoF o/e 0.79

Max pathogenic AF

—

Genomic locus

chr20:35,626,031-35,664,956

External References & Databases

Ensembl (ENSG00000214078)

Transcript & Mutation Effects

hg38 • Region Span ~38.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CPNE1 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 218

not providedTotal: 10

RBM12-related disorderTotal: 7

Schizophrenia 19Total: 5

Neurodevelopmental delayTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_152925.3. 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			2 clinvar	2 clinvar		4
missense			86 clinvar	4 clinvar		90
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	94	6	0	100

Highest pathogenic variant AF is 0.0000013723464

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 58 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_152925.3	RefSeq	NP_690902.1	15	MANE Select
ENST00000397443.7	Ensembl	ENSP00000380585.1	15	MANE Select
NM_001198863.2	RefSeq	NP_001185792.1	15	Standard
NM_003915.6	RefSeq	NP_003906.2	16	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Neutrophil degranulation
Metabolism of lipids
Innate Immune System
Immune System
Metabolism

Biological Process

proteolysis
lipid metabolic process
negative regulation of gene expression
vesicle-mediated transport
regulation of I-kappaB kinase/NF-kappaB signaling

Molecular Function

phosphatidylserine binding
endopeptidase activity
transporter activity
calcium ion binding
protein binding

Cellular Component

nucleus
nucleoplasm
cytoplasm
cytosol
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000317677
Coding exons: 16
Length: 38926
Individuals with no LoFs: 100225
Homozygous LoFs: 1579
Heterozygous LoFs: 23944
Defined: 125748
p: 0.107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0942	316	321	0.985	0.0000193	3521
Missense (PolyPhen)		116	117.48	0.98737		1442
Synonymous	1.12	106	122	0.871	0.00000689	1079
Loss of Function	1.08	25	31.6	0.792	0.00000156	349

Population LoF Frequency

Population	CAF	p-value	Status
African	0.096	0.097	notable
Latino/Admixed American	0.10	0.10	notable
Ashkenazi Jewish	0.14	0.14	notable
East Asian	0.083	0.082	notable
Finnish	0.073	0.074	notable
European (Non-Finnish)	0.11	0.10	notable
South Asian	0.16	0.16	notable
Other	0.12	0.11	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Calcium-dependent phospholipid-binding protein that plays a role in calcium-mediated intracellular processes (PubMed:14674885). Involved in the TNF-alpha receptor signaling pathway in a calcium-dependent manner (PubMed:14674885). Exhibits calcium-dependent phospholipid binding properties (PubMed:9430674, PubMed:19539605). Plays a role in neuronal progenitor cell differentiation; induces neurite outgrowth via a AKT-dependent signaling cascade and calcium-independent manner (PubMed:23263657, PubMed:25450385). May recruit target proteins to the cell membrane in a calcium-dependent manner (PubMed:12522145). May function in membrane trafficking (PubMed:9430674). Involved in TNF-alpha- induced NF-kappa-B transcriptional repression by inducing endoprotease processing of the transcription factor NF-kappa-B p65/RELA subunit (PubMed:18212740). Also induces endoprotease processing of NF-kappa-B p50/NFKB1, p52/NFKB2, RELB and REL (PubMed:18212740). {ECO:0000269|PubMed:12522145, ECO:0000269|PubMed:14674885, ECO:0000269|PubMed:18212740, ECO:0000269|PubMed:19539605, ECO:0000269|PubMed:23263657, ECO:0000269|PubMed:25450385, ECO:0000269|PubMed:9430674}.;

Recessive Scores

pRec: 0.186

Intolerance Scores

LoFtool: 0.866
RVIS EVS: 1
RVIS percentile EVS: 90.72

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.875

Gene Damage Prediction

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