Familial hyperparathyroidism or hypocalciuric hypercalcaemia
Gene: AP2S1

AP2S1 (adaptor related protein complex 2 sigma 1 subunit)
EnsemblGeneIds (GRCh38): ENSG00000042753
EnsemblGeneIds (GRCh37): ENSG00000042753
OMIM: 602242, Gene2Phenotype
AP2S1 is in 5 panels

3 reviews

Arina Puzriakova (Genomics England Curator)

Additional evidence from mouse model that is representative for FHH3 in humans:
PMID: 33729479 - Hannan et al 2021 - Created mice with the AP2S1 p.Arg15Leu mutation, which causes the most severe FHH3 phenotype. Heterozygous (Ap2s1+/L15) mice were viable, homozygous mice died perinatally, The heterozygous mice showed hypercalcaemia, hypermagnesaemia, hypophosphataemia. The phenotype can be ameliorated by treatment with cinacalcet.
Created: 8 Mar 2022, 3:36 p.m. | Last Modified: 8 Mar 2022, 3:36 p.m.

Panel Version: 2.16

Phenotypes
Hypocalciuric hypercalcemia, type III, OMIM:600740

Publications

33729479

Created: 8 Mar 2022, 3:36 p.m.
Last Modified: 8 Mar 2022, 3:36 p.m.
Panel version: 2.16

Ivone Leong (Genomics England Curator)

Submitted on behalf of Treen Cranston (Oxford): codon 15 should be covered.
Created: 31 Jul 2019, 2:14 p.m. | Last Modified: 31 Jul 2019, 2:14 p.m.

Panel Version: 1.3

As discussed in the GMS Endocrinology Specialist Test Group webex call 28th Jan 2019: The Specialist Test Group agreed that there is enough evidence to rate this gene green.
Created: 29 Jan 2019, 11:51 a.m.

Comment on list classification: Have given AP2S1 a green gene status as recommended by Treena Cranston's (Oxford) review.
Created: 11 Jan 2019, 9:12 a.m.

Created: 11 Jan 2019, 9:12 a.m.

Panel version: 1.3

Treena Cranston (Oxford)

pathogenic mutations affecting codon 15 of AP2S1 are causative of FHH3. There can be clinical overlap between hyperparathyroidism and FHH and as such AP2S1, which is a simple test should be considered as part of the differential diagnosis. In our own cohort of individuals referred for the hyperparathyroidism panel we have detected 2 individuals with pathogenic AP2S1 variants (unpublished).
Due to clinical overlap and clinical management of the different conditions, Inclusion of the FHH genes on hyperparathyroidism gene panel lists is a recommendation from an international workshop: Diagnosis of Asymptomatic Primary Hyperparathyroidism: Proceedings of the Fourth International Workshop PMID: 25162666
Sources: Expert Review
Created: 9 Jan 2019, 6:07 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
FHH3

Publications

PMID: 25162666
PMID: 28740527

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

Created: 9 Jan 2019, 6:07 p.m.

Panel version: 0.11

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Sources

Expert Review Green

Phenotypes

Hypocalciuric hypercalcemia, type III, OMIM:600740

OMIM

602242

Clinvar variants

Variants in AP2S1

Penetrance

unknown

Publications

Panels with this gene

History Filter Activity

8 Mar 2022, Gel status: 3

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: AP2S1 were set to 25162666; 28740527; 26963950

8 Mar 2022, Gel status: 3

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: AP2S1 were changed from Hypocalciuric hypercalcemia, type III, 600740 to Hypocalciuric hypercalcemia, type III, OMIM:600740

30 Jan 2019, Gel status: 3