ARHGAP35

Rho GTPase activating protein 35, the group of Rho GTPase activating proteins

Basic information

Region (hg38): 19:46860997-47005077

Previous symbols: [ "GRLF1" ]

Links

ENSG00000160007 ∙ NCBI:2909 ∙ OMIM:605277 ∙ HGNC:4591 ∙ Uniprot:Q9NRY4 ∙ 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 ARHGAP35 gene.

• Bilateral microphthalmos (1 variants)
• Irido-corneo-trabecular dysgenesis (1 variants)
• Neurodevelopmental disorder (1 variants)
• Unilateral microphthalmos (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ARHGAP35 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					3	3
missense		1	53	3		57
nonsense	2	5				7
start loss						0
frameshift	2	4	1			7
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	4	10	54	3	3

Variants in ARHGAP35

This is a list of pathogenic ClinVar variants found in the ARHGAP35 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-46918718-A-C		not specified	Uncertain significance (Mar 28, 2024)
19-46918820-G-A		not specified	Uncertain significance (Jan 25, 2023)
19-46919000-C-T		Martsolf syndrome 1	Likely pathogenic (Apr 01, 2022)
19-46919001-G-A			Uncertain significance (Aug 05, 2020)
19-46919017-GC-G		Martsolf syndrome 1	Likely pathogenic (Apr 01, 2022)
19-46919027-A-T		Martsolf syndrome 1	Likely pathogenic (Apr 01, 2022)
19-46919050-T-C			Benign (Jun 28, 2017)
19-46919091-T-C		not specified	Uncertain significance (Nov 22, 2022)
19-46919189-AG-A		Martsolf syndrome 1	Likely pathogenic (Apr 01, 2022)
19-46919535-A-G		not specified	Uncertain significance (Sep 26, 2023)
19-46919541-A-G		not specified	Uncertain significance (Jul 26, 2021)
19-46919565-G-A		not specified	Uncertain significance (Dec 06, 2022)
19-46919654-C-G		not specified	Uncertain significance (Sep 25, 2023)
19-46919709-C-T		not specified	Uncertain significance (May 17, 2023)
19-46919913-A-G		not specified	Uncertain significance (Apr 26, 2024)
19-46919946-G-A		not specified	Uncertain significance (Jun 05, 2023)
19-46919973-GA-G			Uncertain significance (May 04, 2017)
19-46919979-C-T		not specified	Uncertain significance (Jan 16, 2024)
19-46919997-A-G		not specified	Uncertain significance (Oct 27, 2022)
19-46920053-A-T		not specified	Uncertain significance (Aug 09, 2021)
19-46920275-C-T		Neurodevelopmental disorder	Likely pathogenic (Jun 24, 2022)
19-46920385-T-G		not specified	Uncertain significance (Jul 20, 2021)
19-46920393-T-C		not specified	Uncertain significance (Mar 23, 2023)
19-46920417-C-T		not specified	Uncertain significance (Mar 12, 2024)
19-46920418-G-A			Benign (Dec 31, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ARHGAP35	protein_coding	protein_coding	ENST00000404338	6	86402

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	6.33e-9	124634	0	4	124638	0.0000160

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.16	510	852	0.599	0.0000497	9949
Missense in Polyphen		136	356.04	0.38197		4119
Synonymous	0.153	334	338	0.989	0.0000206	2906
Loss of Function	6.68	0	52.0	0.00	0.00000310	609

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000290	0.0000290
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000266	0.0000265
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Rho GTPase-activating protein (GAP) (PubMed:19673492, PubMed:28894085). Binds several acidic phospholipids which inhibits the Rho GAP activity to promote the Rac GAP activity (PubMed:19673492). This binding is inhibited by phosphorylation by PRKCA (PubMed:19673492). Involved in cell differentiation as well as cell adhesion and migration, plays an important role in retinal tissue morphogenesis, neural tube fusion, midline fusion of the cerebral hemispheres and mammary gland branching morphogenesis (By similarity). Transduces signals from p21-ras to the nucleus, acting via the ras GTPase-activating protein (GAP) (By similarity). Transduces SRC-dependent signals from cell-surface adhesion molecules, such as laminin, to promote neurite outgrowth. Regulates axon outgrowth, guidance and fasciculation (By similarity). Modulates Rho GTPase-dependent F-actin polymerization, organization and assembly, is involved in polarized cell migration and in the positive regulation of ciliogenesis and cilia elongation (By similarity). During mammary gland development, is required in both the epithelial and stromal compartments for ductal outgrowth (By similarity). Represses transcription of the glucocorticoid receptor by binding to the cis-acting regulatory sequence 5'-GAGAAAAGAAACTGGAGAAACTC-3'; this function is however unclear and would need additional experimental evidences (PubMed:1894621). {ECO:0000250|UniProtKB:P81128, ECO:0000250|UniProtKB:Q91YM2, ECO:0000269|PubMed:1894621, ECO:0000269|PubMed:19673492, ECO:0000269|PubMed:28894085}.
• Pathway: Platelet activation - Homo sapiens (human);Focal adhesion - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Leukocyte transendothelial migration - Homo sapiens (human);Focal Adhesion;Regulation of Actin Cytoskeleton;Developmental Biology;Signaling by PTK6;Signal Transduction;TCR;Rho GTPase cycle;Signaling by Rho GTPases;Sema4D mediated inhibition of cell attachment and migration;EGFR1;SHP2 signaling;Sema4D in semaphorin signaling;Semaphorin interactions;PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases;Signaling by Non-Receptor Tyrosine Kinases;Axon guidance;Signaling events mediated by focal adhesion kinase;PDGFR-beta signaling pathway;EPHA2 forward signaling;Regulation of RhoA activity (Consensus)

Recessive Scores

• pRec: 0.167

Intolerance Scores

• rvis_EVS: -1.81
• rvis_percentile_EVS: 2.17

Haploinsufficiency Scores

• pHI: 0.635
• hipred: Y
• hipred_score: 0.768
• ghis: 0.619

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Arhgap35
• Phenotype: cellular phenotype; growth/size/body region phenotype; embryo phenotype; renal/urinary system phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); pigmentation 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)

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;neural tube closure;transcription, DNA-templated;signal transduction;axon guidance;axonal fasciculation;regulation of actin polymerization or depolymerization;regulation of cell shape;positive regulation of neuron projection development;cell migration;central nervous system neuron axonogenesis;mammary gland development;forebrain development;establishment or maintenance of actin cytoskeleton polarity;cellular response to extracellular stimulus;regulation of actin cytoskeleton organization;negative regulation of Rho protein signal transduction;camera-type eye development;negative regulation of vascular permeability;positive regulation of GTPase activity;wound healing, spreading of cells;positive regulation of cilium assembly;negative regulation of transcription, DNA-templated;regulation of axonogenesis;regulation of small GTPase mediated signal transduction;neuron projection guidance
• Cellular component: nucleus;cytosol;plasma membrane;actin cytoskeleton;ciliary basal body
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;DNA-binding transcription repressor activity, RNA polymerase II-specific;DNA binding;transcription corepressor activity;GTPase activity;GTPase activator activity;GTP binding;phospholipid binding