Severe early-onset obesity

Gene: CPE

Amber List (moderate evidence)

CPE (carboxypeptidase E)
EnsemblGeneIds (GRCh38): ENSG00000109472
EnsemblGeneIds (GRCh37): ENSG00000109472
OMIM: 114855, Gene2Phenotype
CPE is in 3 panels

4 reviews

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There are now sufficient unrelated families (5) reported in literature presenting a relevant phenotype associated with variants in this gene to rate as Green at the next GMS panel update.
Created: 28 Sep 2021, 3:05 p.m. | Last Modified: 28 Sep 2021, 3:05 p.m.
Panel Version: 2.43
Durmaz et al. 2021 (PMID: 32936766) identified the second family with 3 affected sibs with obesity, intellectual disability and hypogonadotropic hypogonadism, and a homozygous nonsense c.405C>A (p.Y135*) variant in CPE.

Bosch et al. 2021 (PMID: 34383079) reported on 4 individuals from 3 additional families harbouring 2 different homozygous truncating variants in this gene. Clinical presentation was prominent for obesity and intellectual disability. Hypogonadotropic hypogonadism was confirmed in one individual and was suspected but not tested for in another two subjects.
Created: 28 Sep 2021, 3:04 p.m. | Last Modified: 28 Sep 2021, 3:04 p.m.
Panel Version: 2.41
Comment on phenotypes: CPE is now associated with a relevant phenotype in OMIM - Intellectual developmental disorder and hypogonadotropic hypogonadism, MIM# 619326
Created: 22 Jun 2021, 2:42 p.m. | Last Modified: 22 Jun 2021, 2:42 p.m.
Panel Version: 2.39

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Intellectual developmental disorder and hypogonadotropic hypogonadism, OMIM:619326

Publications

Ivone Leong (Genomics England Curator)

I don't know

CPE is not associated with any phenotype on OMIM or Gene2Phenotype. PMID: 26120850 reported on a consanguineous Sudanese family with Mendelian pattern of obesity. The proband had childhood onset obesity, ID, T2DM and hypogonadotrophic hypogonadism and was homozygous for truncating mutation. There were 4 other family members who were heterozygous for this variant who were mildly obese but did not have ID or hypogonadotrophic hypogonadism. The proband's phenotype resembles Cpe knockout mouse and fat/fat mouse models. However, there is currently not enough evidence to support a gene-disease association.
Created: 15 Aug 2019, 2:02 p.m. | Last Modified: 15 Aug 2019, 2:02 p.m.
Panel Version: 1.22

Publications

Ismaa Farooqi (University of Cambridge)

Green List (high evidence)

Variants in this GENE are reported as part of current diagnostic practice

Ellen McDonagh (Genomics England Curator)

Comment on list classification: Candidate gene. Gene added by expert reviewer. CPE knockout mice become obese within 10-14 weeks, and develop endocrinological and behavioral deficits (PMID: 15358678, 15870393). Several publications linking variants in the gene to atherosclerosis. Gene not associated with a disease/phenotype in OMIM, Gene2Phenotype, Orphanet or DECIPHER. Obesity HPO term not associated with CPE. No single variants in ClinVar reported in CPE...only structural variants that include this gene and others.
Created: 16 Oct 2016, 10:19 a.m.

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
Phenotypes
  • Intellectual developmental disorder and hypogonadotropic hypogonadism, OMIM:619326
Tags
Q3_21_rating
OMIM
114855
Clinvar variants
Variants in CPE
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

28 Sep 2021, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: cpe has been classified as Amber List (Moderate Evidence).

28 Sep 2021, Gel status: 2

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: CPE were set to 26120850; 15870393; 15358678

28 Sep 2021, Gel status: 2

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q3_21_rating tag was added to gene: CPE.

22 Jun 2021, Gel status: 2

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: CPE were changed from obesity to Intellectual developmental disorder and hypogonadotropic hypogonadism, OMIM:619326

15 Aug 2019, Gel status: 2

Added New Source, Set publications, Status Update

Ivone Leong (Genomics England Curator)

Source Expert Review Amber was added to CPE. Publications for gene CPE were changed from 15358678; 15870393 to 26120850; 15870393; 15358678 Rating Changed from Red List (low evidence) to Amber List (moderate evidence)

25 Oct 2016, Gel status: 1

panel promoted to version 1

Ellen McDonagh (Genomics England Curator)

25/Oct/2016: Panel revised according to expert review and additional curation with internal discussion. Ready to be promoted to version 1.

16 Oct 2016, Gel status: 1

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

16 Oct 2016, Gel status: 1

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for CPE were set to 15358678;15870393

16 Oct 2016, Gel status: 1

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for CPE were set to 15358678;

16 Oct 2016, Gel status: 1

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

27 Dec 2015, Gel status: 0

Added New Source

stephen o'rahilly (university of cambridge)

CPE was added to Significant early-onset obesity +/- other endocrine features and short staturepanel. Sources: Expert list

27 Dec 2015, Gel status: 0

Created

stephen o'rahilly (university of cambridge)

CPE was created by [email protected]