ARHGAP20 (Rho GTPase activating protein 20)

2006-08-01   Claudia Kalla 

DKFZ, Div. Molecular Genetics (B060), Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany

Identity

HGNC
LOCATION
11q23.1
LOCUSID
ALIAS
RARHOGAP
FUSION GENES

DNA/RNA

Atlas Image
Genomic organization (A) and transcript variants (B) of ARHGAP20.
(A) Gene structure (drawn to scale): black boxes represent exons.
(B) Transcripts (drawn to scale): boxes, exons; UTR, untranslated region; light shaded box, coding region; shaded and dark shaded boxes, nucleotide sequences coding for protein domains (PH: pleckstrin homology domain, RA: ras association domain; RhoGAP: RhoGAP domain).

Description

19 exons spanning 136.1 kb genomic DNA.

Transcription

5.9-6.2 kb mRNA, coding sequence: 3.5-3.6 kb
Alternative splicing of the first 5 exons results in the expression of 5 transcript variants (ARHGAP20-1e, ARHGAP20-1d, ARHGAP20-1ad, ARHGAP20-1be, ARHGAP20-1c).

Pseudogene

None.

Proteins

Atlas Image
Schematic representation of ARHGAP20 protein variants as deduced from the transcripts. Hatched box, amino-terminal extension of unknown function; PH: pleckstrin homology domain, RA: ras association domain; RhoGAP: RhoGAP domain.

Description

The amino-terminal region shows significant homology to a pleckstrin homology (PH) domain commonly found in eukaryotic signaling proteins. Adjacent to the PH domain a Ras association (RA) domain is postulated, which is found in proteins involved in GTPase-mediated signaling processes. The central section of the protein contains a RhoGAP domain, which is crucial for the regulation of Rho-like GTPases by Rho GTPase-activating proteins in the course of transmitting diverse intracellular signals.

Expression

Predominantly expressed in brain, but transcripts were also detected in peripheral blood lymphocytes.

Localisation

Cytoplasm

Function

The presence of a RhoGAP domain in combination with PH and RA modules indicates that ARHGAP20 is involved in the regulation of Rho-family GTPases. ARHGAP20 was shown to be activated by Rap1 and to induce inactivation of Rho, resulting in the neurite outgrowth.

Homology

Mouse: RarhoGAP (RhoGAP having the RA domain), Arhgap20.
Rat: RahoGAP (RhoGAP having the RA domain), Arhgap20.

Mutations

Note

Single nucleotide polymorphism 1785T/C (transcript variant ARHGAP20-1ad, AY496263).

Germinal

None detected.

Somatic

In the tumour cells of one case of B-cell chronic lymphocytic leukemia, the missense mutation 2995T>G (S999A; transcript variant ARHGAP20-1ad, AY496263) was found.

Implicated in

Entity name
B-cell chronic lymphocytic leukemia (B-CLL).
Note
In the tumour cells of two B-CLL cases, ARHGAP20 was found affected by translocations that rearranged the gene with BRWD3 (Xq21) and a novel gene on 13q14 (unpublished data), respectively. No fusion transcripts were generated. ARHGAP20 transcript expression is significantly upregulated in B-CLL lymphocytes vs. CD19+ control B cells.
Entity name
Disease
B-cell chronic lymphocytic leukemia (B-CLL).
Cytogenetics
t(X;11)(q21;q23)
Hybrid gene
ARHGAP20 - BRWD3
Fusion protein
None detected.
Entity name
t(11;13)(q23;q14)
Disease
B-cell chronic lymphocytic leukemia (B-CLL).
Cytogenetics
t(11;13)(q23;14)
Hybrid gene
ARHGAP20 - novel gene on 13q14 (unpublished data)
Fusion protein
None detected.

Bibliography

Pubmed IDLast YearTitleAuthors
152340032004Identification of RARhoGAP, a novel putative RhoGAP gene expressed in male germ cells.Curry BJ et al
155436022005Translocation t(X;11)(q13;q23) in B-cell chronic lymphocytic leukemia disrupts two novel genes.Kalla C et al
145329922003Identification and characterization of human KIAA1391 and mouse Kiaa1391 genes encoding novel RhoGAP family proteins with RA domain and ANXL repeats.Katoh M et al
107181982000Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro.Nagase T et al
160146232005RA-RhoGAP, Rap-activated Rho GTPase-activating protein implicated in neurite outgrowth through Rho.Yamada T et al

Other Information

Locus ID:

NCBI: 57569
MIM: 609568
HGNC: 18357
Ensembl: ENSG00000137727

Variants:

dbSNP: 57569
ClinVar: 57569
TCGA: ENSG00000137727
COSMIC: ARHGAP20

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000137727ENST00000260283Q9P2F6
ENSG00000137727ENST00000524756Q9P2F6
ENSG00000137727ENST00000527598Q9P2F6
ENSG00000137727ENST00000528829Q9P2F6
ENSG00000137727ENST00000529591A0A0C4DGG5
ENSG00000137727ENST00000533353Q9P2F6

Expression (GTEx)

0
5
10
15

Pathways

PathwaySourceExternal ID
Signal TransductionREACTOMER-HSA-162582
Signaling by Rho GTPasesREACTOMER-HSA-194315
Rho GTPase cycleREACTOMER-HSA-194840

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
160146232005RA-RhoGAP, Rap-activated Rho GTPase-activating protein implicated in neurite outgrowth through Rho.30
145329922003Identification and characterization of human KIAA1391 and mouse Kiaa1391 genes encoding novel RhoGAP family proteins with RA domain and ANXL repeats.5
215003112011Expression analysis of genes located in the minimally deleted regions of 13q14 and 11q22-23 in chronic lymphocytic leukemia-unexpected expression pattern of the RHO GTPase activator ARHGAP20.2

Citation

Claudia Kalla

ARHGAP20 (Rho GTPase activating protein 20)

Atlas Genet Cytogenet Oncol Haematol. 2006-08-01

Online version: http://atlasgeneticsoncology.org/gene/42979/arhgap20-(rho-gtpase-activating-protein-20)