Autoinflammatory Disorders

Gene: ARPC5

Green List (high evidence)

ARPC5 (actin related protein 2/3 complex subunit 5)
EnsemblGeneIds (GRCh38): ENSG00000162704
EnsemblGeneIds (GRCh37): ENSG00000162704
OMIM: 604227, Gene2Phenotype
ARPC5 is in 4 panels

3 reviews

Bryony Thompson (Royal Melbourne Hospital)

Green List (high evidence)

3 unrelated consanguineous families with homozygous variants and supporting in vitro functional assays. Immune dysregulation is a prominent feature of the condition. The IUIS IEI committee classify it as a disease of immune dysregulation in the subcategory of autoimmunity with or without lymphoproliferation.
Sources: Expert list
Created: 16 Nov 2024, 2:18 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Immunodeficiency 133 with autoimmunity and autoinflammation MIM#620565

Publications

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

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

Four individuals from 3 families reported. In addition to recurrent infections, features of autoinflammation common: haemolytic anaemia, thrombocytopenia, hepatosplenomegaly, leukocytosis, neutrophilia, and elevated acute phase reactants. More variable systemic features may include coeliac disease or enteropathy, ileus, nephropathy, eczema, and dermatomyositis.
Sources: Literature
Created: 20 Nov 2023, 9:27 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Immunodeficiency 133 with autoimmunity and autoinflammation, MIM# 620565

Publications

Paul De Fazio (Victorian Clinical Genetics Services)

Green List (high evidence)

4 individuals from 3 families reported with homozygous LoF variants. All had recurrent and severe infections. Other developmental anomalies were present but seemed variable.

PMID:37349293 reports 2 unrelated patients. Both had scoliosis. One had neurodevelopmental delay and brain atrophy. Patient 1 died at 15yo after a sudden episode of hemoptysis and hematochezia. Patient 2 died at 1yo because of progressive neurologic and respiratory disease; an autopsy was not performed.

PMID:37382373 reports 2 patients from the same family. One had multiple congenital anomalies including a congenital heart defect (CHD) (patent foramen ovale), cleft palate, and hypoplastic corpus callosum. The sibling also had CHD (moderate pulmonary stenosis and atrial septal defect).

Functional studies and a mouse model were supportive of the disease association.
Sources: Literature
Created: 6 Jul 2023, 2:56 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Combined immunodeficiency, ARPC5-related MONDO:0015131

Publications

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

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Expert list
  • Expert Review Green
  • Literature
Phenotypes
  • Immunodeficiency 133 with autoimmunity and autoinflammation, MIM# 620565
OMIM
604227
Clinvar variants
Variants in ARPC5
Penetrance
None
Publications
Panels with this gene

History Filter Activity

20 Nov 2023, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: arpc5 has been classified as Green List (High Evidence).

20 Nov 2023, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: arpc5 has been classified as Green List (High Evidence).

20 Nov 2023, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: ARPC5 was added gene: ARPC5 was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature Mode of inheritance for gene: ARPC5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ARPC5 were set to 37349293; 37382373 Phenotypes for gene: ARPC5 were set to Immunodeficiency 133 with autoimmunity and autoinflammation, MIM# 620565 Review for gene: ARPC5 was set to GREEN