ARHGAP9

Rho GTPase activating protein 9, the group of Pleckstrin homology domain containing|Rho GTPase activating proteins

Basic information

Region (hg38): 12:57472263-57488814

Links

ENSG00000123329 ∙ NCBI:64333 ∙ OMIM:610576 ∙ HGNC:14130 ∙ Uniprot:Q9BRR9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ARHGAP9 gene.

• Inborn genetic diseases (29 variants)
• Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency;Charcot-Marie-Tooth disease axonal type 2U (17 variants)
• not provided (8 variants)
• Charcot-Marie-Tooth disease axonal type 2U;Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency (6 variants)
• not specified (2 variants)
• Hereditary spastic paraplegia (1 variants)
• Spastic paraplegia 70, autosomal recessive (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ARHGAP9 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					1	1
missense			22	2		24
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			20	10	3	33
Total	0	0	42	12	4

Variants in ARHGAP9

This is a list of pathogenic ClinVar variants found in the ARHGAP9 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-57472521-G-C		not specified	Uncertain significance (Mar 17, 2023)
12-57472609-C-G		not specified	Uncertain significance (Jan 07, 2022)
12-57472614-C-T		not specified	Uncertain significance (May 09, 2023)
12-57473639-T-C		not specified	Likely benign (Feb 23, 2023)
12-57473677-C-G		not specified	Uncertain significance (Jun 06, 2023)
12-57474125-G-A		not specified	Uncertain significance (Jun 29, 2023)
12-57474680-G-A		not specified	Uncertain significance (Nov 15, 2021)
12-57474683-A-T		not specified	Uncertain significance (May 31, 2022)
12-57475365-A-G		not specified	Uncertain significance (Oct 12, 2021)
12-57475386-T-G		not specified	Uncertain significance (Oct 05, 2021)
12-57475389-G-A		not specified	Uncertain significance (Sep 16, 2021)
12-57476106-C-T		not specified	Uncertain significance (Feb 16, 2023)
12-57476351-C-G		not specified	Likely benign (Jan 02, 2024)
12-57476372-A-C		Coronary artery spasm 3, susceptibility to	Uncertain significance (Jan 01, 2010)
12-57476450-T-C		not specified	Uncertain significance (Sep 14, 2023)
12-57476616-C-A		not specified	Uncertain significance (Jun 01, 2023)
12-57476621-T-A		not specified	Uncertain significance (Jan 31, 2023)
12-57476638-G-A		not specified	Uncertain significance (Aug 12, 2021)
12-57476893-G-C		not specified	Uncertain significance (May 31, 2023)
12-57477182-C-T		not specified	Uncertain significance (Aug 04, 2023)
12-57477262-C-T		not specified	Uncertain significance (Aug 22, 2023)
12-57477470-G-T		not specified	Uncertain significance (Dec 21, 2023)
12-57477481-G-A		not specified	Uncertain significance (Oct 27, 2023)
12-57477623-G-A		not specified	Uncertain significance (May 31, 2023)
12-57478562-G-A		not specified	Likely benign (Nov 15, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ARHGAP9	protein_coding	protein_coding	ENST00000393791	17	16560

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.94e-11	0.983	125629	0	119	125748	0.000473

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.414	414	438	0.944	0.0000257	4633
Missense in Polyphen		141	184.03	0.76617		1944
Synonymous	1.05	162	180	0.900	0.00000982	1577
Loss of Function	2.37	23	39.0	0.590	0.00000199	411

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00146	0.00143
Ashkenazi Jewish	0.000198	0.000198
East Asian	0.000763	0.000761
Finnish	0.00	0.00
European (Non-Finnish)	0.000525	0.000519
Middle Eastern	0.000763	0.000761
South Asian	0.000231	0.000229
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. Has a substantial GAP activity toward CDC42 and RAC1 and less toward RHOA. Has a role in regulating adhesion of hematopoietic cells to the extracellular matrix. Binds phosphoinositides, and has the highest affinity for phosphatidylinositol 3,4,5-trisphosphate, followed by phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 4,5-bisphosphate. {ECO:0000269|PubMed:11396949}.
• Pathway: Neutrophil degranulation;Signal Transduction;Innate Immune System;Immune System;Rho GTPase cycle;Signaling by Rho GTPases;Regulation of RAC1 activity;Regulation of RhoA activity (Consensus)

Recessive Scores

• pRec: 0.213

Intolerance Scores

• loftool: 0.930
• rvis_EVS: -0.33
• rvis_percentile_EVS: 30.9

Haploinsufficiency Scores

• pHI: 0.141
• hipred: N
• hipred_score: 0.179
• ghis: 0.536

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.356

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Arhgap9

Gene ontology

• Biological process: signal transduction;regulation of GTPase activity;neutrophil degranulation;positive regulation of GTPase activity;regulation of small GTPase mediated signal transduction
• Cellular component: extracellular region;cytoplasm;cytosol;secretory granule lumen
• Molecular function: GTPase activator activity;protein binding;phosphatidylinositol-3,4,5-trisphosphate binding