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.

• not provided (2 variants)
• BDV syndrome (2 variants)
• Blakemore-Durmaz-Vasileiou (BDV) syndrome (1 variants)
• Inborn genetic diseases (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.

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				16	4	20
missense			38	5	3	46
nonsense	3					3
start loss						0
frameshift	1					1
inframe indel						0
splice donor/acceptor (+/-2bp)				1		1
splice region			1	3	1	5
non coding				3		3
Total	4	0	38	25	7

Variants in CPE

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

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

Position	Type	Phenotype	Significance	ClinVar
4-165379227-C-G			Likely benign (Oct 01, 2022)
4-165379235-G-T		CPE-related disorder	Uncertain significance (Jan 01, 2024)
4-165379248-G-T		CPE-related disorder	Likely benign (Jan 12, 2023)
4-165379249-C-A		Inborn genetic diseases	Uncertain significance (Dec 11, 2023)
4-165379261-G-A		CPE-related disorder	Uncertain significance (Jun 06, 2024)
4-165379264-G-A			Uncertain significance (Jul 08, 2022)
4-165379266-A-G		CPE-related disorder	Likely benign (Jun 01, 2021)
4-165379280-G-A		CPE-related disorder • not specified	Uncertain significance (May 13, 2024)
4-165379284-G-T		Inborn genetic diseases • CPE-related disorder	Uncertain significance (Aug 10, 2023)
4-165379287-C-A		CPE-related disorder	Likely benign (Apr 21, 2021)
4-165379289-TGGGCGCCGAAGCCCAGGAGCCCG-T		BDV syndrome	Pathogenic (Nov 01, 2021)
4-165379298-A-C		Inborn genetic diseases	Uncertain significance (Apr 20, 2021)
4-165379309-C-G		CPE-related disorder	Uncertain significance (Aug 01, 2023)
4-165379311-C-T		CPE-related disorder	Likely benign (Feb 28, 2024)
4-165379317-G-C		CPE-related disorder	Likely benign (Oct 19, 2020)
4-165379341-C-G		CPE-related disorder	Likely benign (Apr 27, 2021)
4-165379343-G-A		CPE-related disorder	Uncertain significance (Sep 03, 2024)
4-165379390-C-A		CPE-related disorder	Uncertain significance (Jul 15, 2024)
4-165379428-G-A			Likely benign (Dec 19, 2023)
4-165379436-C-T		CPE-related disorder	Likely benign (Nov 01, 2024)
4-165379454-C-A		CPE-related disorder	Uncertain significance (Dec 18, 2023)
4-165379498-C-T		CPE-related disorder	Likely benign (May 10, 2023)
4-165379513-G-A		CPE-related disorder	Uncertain significance (Jun 14, 2024)
4-165464436-T-C		CPE-related disorder	Likely benign (May 17, 2022)
4-165464443-C-T		Blakemore-Durmaz-Vasileiou (BDV) syndrome • BDV syndrome	Pathogenic (Mar 29, 2024)

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