CPE

carboxypeptidase E, the group of M14 carboxypeptidases|MicroRNA protein coding host genes

Basic information

Region (hg38): 4:165361194-165498547

Links

ENSG00000109472

∙ NCBI:1363 ∙ OMIM:114855 ∙ HGNC:2303 ∙ Uniprot:P16870 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

BDV syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
BDV syndrome (Intellectual developmental disorder and hypogonadotropic hypogonadism)	AR	Endocrine	Among other findings, individuals may manifest with hypothyroidism and hypogonadotropic hypogonadism, and awareness may allow medical treatment of these endocrine diosrders; Related to Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease	Endocrine; Neurologic	26120850; 32936766

ClinVar

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

CPE-related_disorder (101 variants)
not_provided (37 variants)
Inborn_genetic_diseases (36 variants)
BDV_syndrome (6 variants)
not_specified (2 variants)
Blakemore-Durmaz-Vasileiou_(BDV)_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CPE gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001873.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				40 clinvar	4 clinvar	44
missense			73 clinvar	6 clinvar	3 clinvar	82
nonsense	4 clinvar					4
start loss						0
frameshift	2 clinvar	1 clinvar				3
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	6	1	74	46	7

Highest pathogenic variant AF is 0.00000665001

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CPE	protein_coding	protein_coding	ENST00000402744	9	137127

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.992	0.00767	125736	0	10	125746	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.82	180	263	0.684	0.0000138	3120
Missense in Polyphen		62	101.56	0.61047		1133
Synonymous	1.18	84	98.9	0.850	0.00000532	906
Loss of Function	4.10	2	23.4	0.0856	0.00000133	254

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000237	0.000231
European (Non-Finnish)	0.0000272	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.0000331	0.0000327
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

Function: FUNCTION: Removes residual C-terminal Arg or Lys remaining after initial endoprotease cleavage during prohormone processing. Processes proinsulin.;
Pathway: Type I diabetes mellitus - Homo sapiens (human);Peptide hormone metabolism;Metabolism of proteins;Insulin processing;Arf6 trafficking events (Consensus)

Recessive Scores

pRec: 0.253

Intolerance Scores

loftool: 0.392
rvis_EVS: -0.05
rvis_percentile_EVS: 50.22

Haploinsufficiency Scores

pHI: 0.712
hipred: Y
hipred_score: 0.800
ghis: 0.588

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.749

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Cpe
Phenotype: endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype; digestive/alimentary phenotype; muscle phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); reproductive system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);

Gene ontology

Biological process: cardiac left ventricle morphogenesis;cellular protein modification process;peptide metabolic process;neuropeptide signaling pathway;Wnt signaling pathway;protein processing;insulin processing;protein localization to membrane
Cellular component: extracellular space;nucleus;Golgi apparatus;plasma membrane;secretory granule;transport vesicle membrane;neuronal cell body;extracellular exosome;synaptic membrane
Molecular function: carboxypeptidase activity;metallocarboxypeptidase activity;zinc ion binding;neurexin family protein binding;cell adhesion molecule binding