ARHGEF1
Basic information
Region (hg38): 19:41883173-41930150
Links
Phenotypes
GenCC
Source:
- immunodeficiency 62 (Limited), mode of inheritance: Unknown
- immunodeficiency 62 (Limited), mode of inheritance: AR
Clinical Genomic Database
Source:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Immunodeficiency 62 | AR | Allergy/Immunology/Infectious; Oncologic | The condition can involve early-onset, recurrent, and severe infections and diagnosis may allow preventative measures and early and prompt treatment of infections (for example, with IVIG); Cancer has been described, and awareness of an increased risk may allow early diagnosis and management | Allergy/Immunology/Infectious; Oncologic | 30521495 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (744 variants)
- not_specified (130 variants)
- ARHGEF1-related_disorder (17 variants)
- Immunodeficiency_62 (9 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the ARHGEF1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004706.4. 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 | 193 | 204 | ||||
missense | 350 | 10 | 361 | |||
nonsense | 3 | |||||
start loss | 0 | |||||
frameshift | 4 | |||||
splice donor/acceptor (+/-2bp) | 3 | |||||
Total | 0 | 0 | 366 | 203 | 6 |
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
ARHGEF1 | protein_coding | protein_coding | ENST00000337665 | 28 | 47075 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
0.768 | 0.232 | 125728 | 0 | 20 | 125748 | 0.0000795 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 2.83 | 407 | 602 | 0.676 | 0.0000416 | 5945 |
Missense in Polyphen | 118 | 209.8 | 0.56243 | 1995 | ||
Synonymous | 0.701 | 235 | 249 | 0.944 | 0.0000169 | 1902 |
Loss of Function | 5.37 | 11 | 53.2 | 0.207 | 0.00000269 | 583 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.000207 | 0.000207 |
Ashkenazi Jewish | 0.0000994 | 0.0000992 |
East Asian | 0.0000544 | 0.0000544 |
Finnish | 0.000121 | 0.0000924 |
European (Non-Finnish) | 0.0000628 | 0.0000615 |
Middle Eastern | 0.0000544 | 0.0000544 |
South Asian | 0.0000659 | 0.0000653 |
Other | 0.000174 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Seems to play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13) subunits. Acts as GTPase-activating protein (GAP) for GNA12 and GNA13, and as guanine nucleotide exchange factor (GEF) for RhoA GTPase. Activated G alpha 13/GNA13 stimulates the RhoGEF activity through interaction with the RGS-like domain. This GEF activity is inhibited by binding to activated GNA12. Mediates angiotensin-2- induced RhoA activation. {ECO:0000269|PubMed:20098430, ECO:0000269|PubMed:8810315, ECO:0000269|PubMed:9641915, ECO:0000269|PubMed:9641916}.;
- Pathway
- Platelet activation - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Vascular smooth muscle contraction - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);G Protein Signaling Pathways;EGF-EGFR Signaling Pathway;Regulation of Actin Cytoskeleton;G13 Signaling Pathway;Signaling by GPCR;Signal Transduction;pkc-catalyzed phosphorylation of inhibitory phosphoprotein of myosin phosphatase;rho cell motility signaling pathway;rac1 cell motility signaling pathway;Rho GTPase cycle;Signaling by Rho GTPases;NRAGE signals death through JNK;Thromboxane A2 receptor signaling;Death Receptor Signalling;p75 NTR receptor-mediated signalling;G alpha (12/13) signalling events;GPCR downstream signalling;PAR1-mediated thrombin signaling events;LPA receptor mediated events;Cell death signalling via NRAGE, NRIF and NADE;Regulation of RhoA activity
(Consensus)
Recessive Scores
- pRec
- 0.150
Intolerance Scores
- loftool
- 0.217
- rvis_EVS
- -1.84
- rvis_percentile_EVS
- 2.07
Haploinsufficiency Scores
- pHI
- 0.109
- hipred
- Y
- hipred_score
- 0.654
- ghis
- 0.611
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.960
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Arhgef1
- Phenotype
- immune 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); muscle phenotype; homeostasis/metabolism phenotype;
Gene ontology
- Biological process
- G protein-coupled receptor signaling pathway;Rho protein signal transduction;cell population proliferation;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;plasma membrane
- Molecular function
- G protein-coupled receptor binding;RNA binding;guanyl-nucleotide exchange factor activity;Rho guanyl-nucleotide exchange factor activity;GTPase activator activity;protein binding