Hereditary neuropathy or pain disorder
Gene: ARHGAP19EnsemblGeneIds (GRCh38): ENSG00000213390
EnsemblGeneIds (GRCh37): ENSG00000213390
OMIM: 611587, Gene2Phenotype
ARHGAP19 is in 2 panels
2 reviews
Achchuthan Shanmugasundram (Genomics England Curator)
Comment on list classification: As reviewed by Alexander Rossor, there are multiple unrelated families reported with biallelic ARHGAP19 variants and with motor-predominant neuropathy. Hence, this gene should be promoted to green rating in the next GMS update.Created: 28 Oct 2025, 4:52 p.m. | Last Modified: 28 Oct 2025, 4:52 p.m.
Panel Version: 7.29
PMID:41086021 (2025) reported the identification of 16 different biallelic variants in ARHGAP19 gene in 25 individuals from 20 unrelated families. The variants included missense and nonsense variants both within and outside the functional GAP domain. The patients had a motor-predominant neuropathy with age of onset almost exclusively in the first two decades of life. The clinical phenotype was generally length-dependent but there are some unusual features, including frequent conduction slowing +/- conduction block, prominent asymmetry, subacute deterioration in some individuals, and upper limb onset.
In vitro biochemical and cellular assays showed GAP domain variants cause loss of protein function. Transcriptomic studies showed loss-of-function altered expression of genes linked to 3 cellular pathways, compared to controls. In addition, iPSC-derived motor neurons showed reduced ARHGAP19 expression. In vivo studies from zebrafish and drosophila loss of function models showed movement deficits.
There was no genotype-phenotype correlation observed in LOF variants reported in 'GAP' domain and outside of this domain.
This gene has not yet been associated with any relevant phenotypes either in OMIM or in Gene2Phenotype (records accessed on 28 October 2025). This gene is rated green on the 'Hereditary Neuropathy_CMT - isolated' panel in PanelApp Australia (https://panelapp-aus.org/panels/3069/gene/ARHGAP19/)Created: 28 Oct 2025, 4:50 p.m. | Last Modified: 28 Oct 2025, 4:50 p.m.
Panel Version: 7.27
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
motor peripheral neuropathy, MONDO:0002316
Publications
Alexander Rossor (UCL Institute of Neurology)
multiple affected families
Sources: Expert listCreated: 27 Oct 2025, 4:57 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
motor axonal neuropathy
Publications
Details
- Mode of Inheritance
- BIALLELIC, autosomal or pseudoautosomal
- Sources
-
- Expert Review Amber
- Phenotypes
-
- motor peripheral neuropathy, MONDO:0002316
- Tags
- OMIM
- 611587
- Clinvar variants
- Variants in ARHGAP19
- Penetrance
- Complete
- Publications
- Panels with this gene
History Filter Activity
Added Tag
Achchuthan Shanmugasundram (Genomics England Curator)Tag Q3_25_NHS_review tag was added to gene: ARHGAP19.
Added Tag
Achchuthan Shanmugasundram (Genomics England Curator)Tag Q3_25_promote_green tag was added to gene: ARHGAP19.
Entity classified by Genomics England curator
Achchuthan Shanmugasundram (Genomics England Curator)Gene: arhgap19 has been classified as Amber List (Moderate Evidence).
Set Phenotypes
Achchuthan Shanmugasundram (Genomics England Curator)Phenotypes for gene: ARHGAP19 were changed from motor axonal neuropathy to motor peripheral neuropathy, MONDO:0002316
Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance
Alexander Rossor (UCL Institute of Neurology)gene: ARHGAP19 was added gene: ARHGAP19 was added to Hereditary neuropathy or pain disorder. Sources: Expert list Mode of inheritance for gene: ARHGAP19 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ARHGAP19 were set to 41086021 Phenotypes for gene: ARHGAP19 were set to motor axonal neuropathy Penetrance for gene: ARHGAP19 were set to Complete Review for gene: ARHGAP19 was set to GREEN