ARHGEF12

Rho guanine nucleotide exchange factor 12, the group of Dbl family Rho GEFs|PDZ domain containing

Basic information

Region (hg38): 11:120336413-120489937

Links

ENSG00000196914 ∙ NCBI:23365 ∙ OMIM:604763 ∙ HGNC:14193 ∙ Uniprot:Q9NZN5 ∙ 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 ARHGEF12 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ARHGEF12 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	2	3
missense			57	4	1	62
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	58	5	3

Variants in ARHGEF12

This is a list of pathogenic ClinVar variants found in the ARHGEF12 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-120337262-A-G		not specified	Uncertain significance (Aug 17, 2022)
11-120407741-T-G		not specified	Uncertain significance (Nov 30, 2022)
11-120407800-C-T		not specified	Uncertain significance (Mar 31, 2023)
11-120409441-G-A		not specified	Uncertain significance (Dec 05, 2022)
11-120420770-G-A		not specified	Uncertain significance (Apr 07, 2023)
11-120424413-A-G		not specified	Likely benign (Feb 16, 2023)
11-120428135-A-G		not specified	Uncertain significance (Nov 18, 2022)
11-120428158-A-G		not specified	Uncertain significance (Oct 05, 2023)
11-120428210-G-T		not specified	Uncertain significance (Jun 28, 2022)
11-120429485-A-C		not specified	Uncertain significance (Feb 17, 2023)
11-120429739-C-T			Benign (Dec 31, 2019)
11-120431787-C-T		not specified	Uncertain significance (May 05, 2023)
11-120431849-G-A		not specified	Uncertain significance (Jan 24, 2024)
11-120431852-C-G		not specified	Uncertain significance (Dec 27, 2022)
11-120431879-G-A		not specified	Uncertain significance (Sep 29, 2023)
11-120431888-C-T		not specified	Uncertain significance (Oct 25, 2023)
11-120431892-C-T		not specified	Uncertain significance (Jun 07, 2024)
11-120431918-T-A			Benign (May 18, 2018)
11-120437308-A-G		not specified	Uncertain significance (May 09, 2022)
11-120440212-A-C		not specified	Uncertain significance (Sep 22, 2022)
11-120441755-C-T		not specified	Uncertain significance (Jun 21, 2022)
11-120441756-G-A		not specified	Uncertain significance (Feb 21, 2024)
11-120441812-A-G		not specified	Uncertain significance (Jul 20, 2022)
11-120442124-C-A		not specified	Uncertain significance (Jan 03, 2024)
11-120442135-A-G		not specified	Uncertain significance (Dec 21, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ARHGEF12	protein_coding	protein_coding	ENST00000397843	41	152859

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	1.00e-8	124776	0	20	124796	0.0000801

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.25	572	836	0.684	0.0000456	10095
Missense in Polyphen		94	221.36	0.42464		2610
Synonymous	1.50	258	291	0.888	0.0000149	2916
Loss of Function	8.08	10	94.9	0.105	0.00000517	1131

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000246	0.000246
Ashkenazi Jewish	0.000100	0.0000993
East Asian	0.000223	0.000223
Finnish	0.00	0.00
European (Non-Finnish)	0.0000625	0.0000618
Middle Eastern	0.000223	0.000223
South Asian	0.0000654	0.0000654
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13). Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPase and may act as GTPase-activating protein (GAP) for GNA12 and GNA13. {ECO:0000269|PubMed:11094164}.
• Pathway: Platelet activation - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Axon guidance - Homo sapiens (human);Vascular smooth muscle contraction - Homo sapiens (human);C-type lectin receptor signaling pathway - Homo sapiens (human);Tuberculosis - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Developmental Biology;Signaling by GPCR;Signal Transduction;Rho GTPase cycle;Signaling by Rho GTPases;Sema4D induced cell migration and growth-cone collapse;Sema4D in semaphorin signaling;NRAGE signals death through JNK;Semaphorin interactions;Death Receptor Signalling;p75 NTR receptor-mediated signalling;Axon guidance;G alpha (12/13) signalling events;GPCR downstream signalling;Cell death signalling via NRAGE, NRIF and NADE;Regulation of RhoA activity (Consensus)

Intolerance Scores

• loftool: 0.241
• rvis_EVS: -0.32
• rvis_percentile_EVS: 30.94

Haploinsufficiency Scores

• pHI: 0.471
• hipred: Y
• hipred_score: 0.822
• ghis: 0.541

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Arhgef12
• Phenotype: immune system 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); 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); hematopoietic 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); embryo phenotype; cellular phenotype; muscle phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: G protein-coupled receptor signaling pathway;Rho protein signal transduction;regulation of Rho protein signal transduction;positive regulation of apoptotic process;positive regulation of GTPase activity;regulation of small GTPase mediated signal transduction
• Cellular component: cytoplasm;cytosol;membrane;extracellular exosome
• Molecular function: G protein-coupled receptor binding;guanyl-nucleotide exchange factor activity;Rho guanyl-nucleotide exchange factor activity;GTPase activator activity;protein binding