Genes in panel
STRs in panel
Prev Next

Primary immunodeficiency

Gene: AP3D1

Amber List (moderate evidence)

AP3D1 (adaptor related protein complex 3 delta 1 subunit)
EnsemblGeneIds (GRCh38): ENSG00000065000
EnsemblGeneIds (GRCh37): ENSG00000065000
OMIM: 607246, Gene2Phenotype
AP3D1 is in 7 panels

3 reviews

Eleanor Williams (Genomics England Curator)

I don't know

Comment on list classification: Changing the rating from red to amber. Two cases now reported.
Created: 3 Nov 2020, 6:27 p.m. | Last Modified: 3 Nov 2020, 6:27 p.m.
Panel Version: 2.369
Provisionally associated with Hermansky-Pudlak syndrome 10 #617050 (AR) in OMIM.

PMID: 30472485 - Mohammad et al 2019 - 1 family with parents who were first cousins with three affected children who presented similarly with severe seizures, developmental delay, albinism, and immunodeficiency. Whole exome sequencing identified homozygosity for AP3D1 deleterious sequence variant (NM_001261826.3:c.1978delG: p.Ala660Argfs*54) which co-segregated with the phenotype. The variant is not found in the gnomAD database or in an in-house database of 284 exome or Middle Eastern population specific database.

PMID: 26744459 - Ammann et al 2016 - report a patient with consanguineous Turkish parents presenting with albinism, neutropenia, immunodeficiency, neurodevelopmental delay, generalized seizures, and impaired hearing. Whole exome sequencing identified a homozygous mutation in AP3D1 (c.3565_3566delGT) that leads to destabilization of the adaptor protein 3 (AP3) complex.
Created: 3 Nov 2020, 6:26 p.m. | Last Modified: 3 Nov 2020, 6:26 p.m.
Panel Version: 2.368
The following PubMed IDs were added to gene AP3D1 (OMIM gene MIM#607246): 30472485;26744459. These publications have been associated with the gene by the immunedysregulation subgroup of the Human Phenotype Ontology Immune Mediated Disorders Consortium (https://hpo-immune-mediated-disorders.groups.io/g/update) in August 2020.
Created: 13 Oct 2020, 9:36 a.m. | Last Modified: 13 Oct 2020, 9:36 a.m.
Panel Version: 2.208

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hermansky-Pudlak syndrome 10, 617050

Publications

Sophie Hambleton (Newcastle University)

Red List (low evidence)

Very likely to be disease-associated but only one patient described to date
Created: 11 Jun 2018, 4:47 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hermansky-Pudlak syndrome; albinism; neutropenia; neuordevelopmental delay; seizures

Publications

Louise Daugherty (Genomics England Curator)

Red List (low evidence)

OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): AP3D1 .PanelApp HGNC gene symbol check: AP3D1 . IUIS Disease: Hermansky-Pudlak syndrome, type 10 . IUIS Inheritance: AR .T cells: N/A, .B cells: Normal, .IUIS Other affected cells: N/A. IUIS Associated features: Oculocutaneous albinism, severe neutropenia, recurrent infections, seizures, hearing loss and neurodevelopmental delay. IUIS Major category: Diseases of Immune Dysregulation. IUIS Subcategory: FHL Syndromes with Hypopigmentation
Created: 2 Jul 2018, 10:35 a.m.
External expert review notes Red status as there is currently only one reported case, so I have kept this gene Red on this panel
Created: 12 Jun 2018, 3:31 p.m.
Comment on phenotypes: Added phenotypes suggested from external expert review.
Created: 12 Jun 2018, 10:23 a.m.
Neutropenia and/or immune defects have been associated with AP3 deficient HPS, including individuals with pathogenic variants in AP3B1 (and AP3D1) PMID:16507770,28585318,26744459. Not enough evidence to date to update rating from Red, currently only one reported case of HSP10 in a boy, born of consanguineous Turkish parents (PMID: 26744459)
Created: 11 May 2018, 10:56 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
?Hermansky-Pudlak syndrome 10, 617050; HSP10; Immunodeficient HPS; Hermansky-Pudlak syndrome with neutropenia

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Other
  • IUIS Classification December 2019
  • IUIS Classification February 2018
  • Literature
Phenotypes
  • Oculocutaneous albinism, recurrent infections, seizures, hearing loss and neurodevelopmental delay
  • Diseases of Immune Dysregulation
  • Hermansky-Pudlak syndrome with neutropenia
  • Oculocutaneous albinism, severe neutropenia, recurrent infections, seizures, hearing loss and neurodevelopmental delay
  • albinism
  • HSP10
  • seizures
  • neutropenia
  • Immunodeficient HPS
  • neuordevelopmental delay
  • Hermansky-Pudlak syndrome
  • ?Hermansky-Pudlak syndrome 10, 617050
OMIM
607246
Clinvar variants
Variants in AP3D1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

3 Nov 2020, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: ap3d1 has been classified as Amber List (Moderate Evidence).

13 Oct 2020, Gel status: 1

Added New Source, Set publications

Eleanor Williams (Genomics England Curator)

Source Other was added to AP3D1. Publications for gene AP3D1 were updated from 32048120; 26744459; 32086639 to 32086639; 26744459; 30472485; 32048120

28 Feb 2020, Gel status: 1

Added New Source, Set Phenotypes, Set publications

Louise Daugherty (Genomics England Curator)

Source IUIS Classification December 2019 was added to AP3D1. Added phenotypes Oculocutaneous albinism, recurrent infections, seizures, hearing loss and neurodevelopmental delay for gene: AP3D1 Publications for gene AP3D1 were updated from 26744459 to 32048120; 26744459; 32086639

12 Jul 2018, Gel status: 1

Panel promoted to version 1.0

Louise Daugherty (Genomics England Curator)

2018-07-12 Louise Daugherty (Genomics England Curator) promoted panel to v1.0. Reviews were assessed, and panel was revised according to expert reviews and further in-house curation based on PanelApp guidelines. Previous panels (A- or hypo-gammaglobulinaemia, Congenital neutropaenia, Agranulocytosis, Combined B and T cell defect, Inherited complement deficiency and SCID panels) that were merged with this panel, were checked again for any changes/new reviews prior to versioning of this panel, these merged panels are now retired/made internal.

1 Jul 2018, Gel status: 1

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene AP3D1 were set to ?Hermansky-Pudlak syndrome 10, 617050, HSP10, Immunodeficient HPS, Hermansky-Pudlak syndrome with neutropenia, Hermansky-Pudlak syndrome, albinism, neutropenia, neuordevelopmental delay, seizures, Oculocutaneous albinism, severe neutropenia, recurrent infections, seizures, hearing loss and neurodevelopmental delay, Diseases of Immune Dysregulation

26 Jun 2018, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

IUIS Classification February 2018 was added to AP3D1. Panel: Primary immunodeficiency disorders

12 Jun 2018, Gel status: 1

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: ap3d1 has been classified as Red List (Low Evidence).

12 Jun 2018, Gel status: 1

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: AP3D1 were set to ?Hermansky-Pudlak syndrome 10, 617050; HSP10; Immunodeficient HPS; Hermansky-Pudlak syndrome with neutropenia; Hermansky-Pudlak syndrome; albinism; neutropenia; neuordevelopmental delay; seizures

11 May 2018, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

AP3D1 was added to Primary immunodeficiency disorders panel. Sources: Literature

11 May 2018, Gel status: 1

Created

Louise Daugherty (Genomics England Curator)

AP3D1 was created by Louise Daugherty