ARHGDIA

Rho GDP dissociation inhibitor alpha

Basic information

Region (hg38): 17:81867719-81871378

Previous symbols: [ "GDIA1" ]

Links

ENSG00000141522

∙ NCBI:396 ∙ OMIM:601925 ∙ HGNC:678 ∙ Uniprot:P52565 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

nephrotic syndrome, type 8 (Moderate), mode of inheritance: AR
familial idiopathic steroid-resistant nephrotic syndrome (Supportive), mode of inheritance: AD
nephrotic syndrome, type 8 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Nephrotic syndrome, type 8	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Renal	23434736; 23867502
Renal transplant has been described

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ARHGDIA gene.

not_provided (31 variants)
Inborn_genetic_diseases (24 variants)
ARHGDIA-related_disorder (7 variants)
Nephrotic_syndrome,_type_8 (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ARHGDIA gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004309.6. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	13 clinvar	2 clinvar	16
missense	1 clinvar		31 clinvar			32
nonsense	1 clinvar					1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	2	0	33	13	2

Highest pathogenic variant AF is 0.0000027368055

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ARHGDIA	protein_coding	protein_coding	ENST00000269321	5	3686

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0364	0.932	125734	0	6	125740	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.20	87	125	0.697	0.00000748	1329
Missense in Polyphen		23	42.853	0.53672		522
Synonymous	-3.35	87	55.3	1.57	0.00000374	382
Loss of Function	1.86	4	10.5	0.380	5.75e-7	117

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.0000996	0.0000992
East Asian	0.000109	0.000109
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.00000879	0.00000879
Middle Eastern	0.000109	0.000109
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Controls Rho proteins homeostasis. Regulates the GDP/GTP exchange reaction of the Rho proteins by inhibiting the dissociation of GDP from them, and the subsequent binding of GTP to them. Retains Rho proteins such as CDC42, RAC1 and RHOA in an inactive cytosolic pool, regulating their stability and protecting them from degradation. Actively involved in the recycling and distribution of activated Rho GTPases in the cell, mediates extraction from membranes of both inactive and activated molecules due its exceptionally high affinity for prenylated forms. Through the modulation of Rho proteins, may play a role in cell motility regulation. In glioma cells, inhibits cell migration and invasion by mediating the signals of SEMA5A and PLXNB3 that lead to inactivation of RAC1. {ECO:0000269|PubMed:20400958, ECO:0000269|PubMed:23434736}.;
Disease: DISEASE: Nephrotic syndrome 8 (NPHS8) [MIM:615244]: A form of nephrotic syndrome, a renal disease clinically characterized by progressive renal failure, severe proteinuria, hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show diffuse mesangial sclerosis, with small glomeruli, hypercellularity, increased extracellular matrix, and contracted/collapsed glomerular tufts surrounded by immature or abnormal podocytes. {ECO:0000269|PubMed:23434736}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Neurotrophin signaling pathway - Homo sapiens (human);Vasopressin-regulated water reabsorption - Homo sapiens (human);miR-targeted genes in epithelium - TarBase;miR-targeted genes in leukocytes - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Signal Transduction;Rho GTPase cycle;Signaling by Rho GTPases;Regulation of RAC1 activity;Death Receptor Signalling;Axonal growth stimulation;Axonal growth inhibition (RHOA activation);p75NTR regulates axonogenesis;p75 NTR receptor-mediated signalling;Regulation of CDC42 activity;PAR1-mediated thrombin signaling events;RAC1 signaling pathway;CDC42 signaling events;p75(NTR)-mediated signaling;PDGFR-beta signaling pathway;Regulation of RhoA activity (Consensus)

Intolerance Scores

loftool: 0.222
rvis_EVS: -0.25
rvis_percentile_EVS: 35.42

Haploinsufficiency Scores

pHI: 0.109
hipred: Y
hipred_score: 0.783
ghis: 0.648

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.973

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Arhgdia
Phenotype: immune system phenotype; renal/urinary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype;

Zebrafish Information Network

Gene name: arhgdia
Affected structure: whole organism
Phenotype tag: abnormal
Phenotype quality: edematous

Gene ontology

Biological process: negative regulation of cell adhesion;Rho protein signal transduction;regulation of Rho protein signal transduction;negative regulation of apoptotic process;positive regulation of GTPase activity;negative regulation of axonogenesis;positive regulation of axonogenesis;regulation of small GTPase mediated signal transduction;semaphorin-plexin signaling pathway;regulation of actin cytoskeleton reorganization
Cellular component: cytosol;cytoskeleton;membrane;extracellular exosome
Molecular function: Rho GDP-dissociation inhibitor activity;GTPase activator activity;protein binding;Rac GTPase binding