RACGAP1
Rac GTPase activating protein 1
Basic information
Region (hg38): 12:49976922-50033136
Links
Phenotypes
GenCC
Source:
No genCC data.
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Anemia, congenital dyserythropoietic, type IIIb, autosomal recessive | AR | Hematologic | The condition can involve clincially significant anemia requiring interventions such as blood transfusions, and awareness may allow prompt diagnosis and management | Hematologic | 34818416; 36200420 |
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the RACGAP1 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 | |||||
| missense | 23 | 23 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 1 | 1 | ||||
| non coding | 13 | 13 | ||||
| Total | 0 | 0 | 23 | 1 | 13 |
Variants in RACGAP1
This is a list of pathogenic ClinVar variants found in the RACGAP1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 12-49990335-C-T | not specified | Uncertain significance (Jan 04, 2024) | ||
| 12-49990388-T-C | Benign (Jun 20, 2021) | |||
| 12-49990566-T-C | Benign (Jun 20, 2021) | |||
| 12-49990686-A-G | Benign (Jun 10, 2021) | |||
| 12-49990711-C-T | not specified | Uncertain significance (Mar 18, 2024) | ||
| 12-49990783-A-G | not specified | Uncertain significance (Mar 16, 2022) | ||
| 12-49991880-T-C | Benign (Jun 19, 2021) | |||
| 12-49992052-G-A | not specified | Uncertain significance (Sep 29, 2023) | ||
| 12-49992061-C-T | not specified | Uncertain significance (Dec 01, 2022) | ||
| 12-49992085-T-A | not specified | Uncertain significance (Feb 15, 2023) | ||
| 12-49992232-C-T | Benign (Nov 12, 2018) | |||
| 12-49992291-T-C | not specified | Uncertain significance (Oct 06, 2021) | ||
| 12-49992505-G-GA | Benign (Jun 20, 2021) | |||
| 12-49992576-T-C | Likely benign (Jul 01, 2022) | |||
| 12-49992604-T-C | not specified | Uncertain significance (Dec 20, 2023) | ||
| 12-49994087-C-T | Benign (Jun 21, 2021) | |||
| 12-49994172-A-G | not specified | Uncertain significance (Dec 08, 2023) | ||
| 12-49994176-G-A | Anemia, congenital dyserythropoietic, type IIIb, autosomal recessive • Anemia, congenital dyserythropoietic, type IIIb | Pathogenic (Aug 11, 2023) | ||
| 12-49994236-C-G | not specified | Uncertain significance (Feb 27, 2023) | ||
| 12-49994283-A-T | Anemia, congenital dyserythropoietic, type IIIb | Pathogenic (Aug 11, 2023) | ||
| 12-49994298-C-T | not specified | Uncertain significance (Mar 15, 2024) | ||
| 12-49994470-T-A | not specified | Uncertain significance (Sep 27, 2022) | ||
| 12-49997093-A-C | not specified | Uncertain significance (Aug 12, 2021) | ||
| 12-49997096-G-C | not specified | Uncertain significance (Dec 28, 2022) | ||
| 12-49997102-G-A | not specified | Uncertain significance (Feb 05, 2024) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| RACGAP1 | protein_coding | protein_coding | ENST00000434422 | 16 | 56214 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.00170 | 0.998 | 125704 | 0 | 44 | 125748 | 0.000175 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.01 | 248 | 354 | 0.700 | 0.0000192 | 4151 |
| Missense in Polyphen | 52 | 95.416 | 0.54498 | 1219 | ||
| Synonymous | 0.349 | 115 | 120 | 0.959 | 0.00000565 | 1240 |
| Loss of Function | 3.85 | 12 | 37.4 | 0.321 | 0.00000233 | 388 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000185 | 0.000185 |
| Ashkenazi Jewish | 0.000298 | 0.000298 |
| East Asian | 0.000326 | 0.000326 |
| Finnish | 0.000554 | 0.000554 |
| European (Non-Finnish) | 0.000123 | 0.000123 |
| Middle Eastern | 0.000326 | 0.000326 |
| South Asian | 0.000164 | 0.000163 |
| Other | 0.000163 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Component of the centralspindlin complex that serves as a microtubule-dependent and Rho-mediated signaling required for the myosin contractile ring formation during the cell cycle cytokinesis. Required for proper attachment of the midbody to the cell membrane during cytokinesis. Plays key roles in controlling cell growth and differentiation of hematopoietic cells through mechanisms other than regulating Rac GTPase activity. Also involved in the regulation of growth-related processes in adipocytes and myoblasts. May be involved in regulating spermatogenesis and in the RACGAP1 pathway in neuronal proliferation. Shows strong GAP (GTPase activation) activity towards CDC42 and RAC1 and less towards RHOA. Essential for the early stages of embryogenesis. May play a role in regulating cortical activity through RHOA during cytokinesis. May participate in the regulation of sulfate transport in male germ cells. {ECO:0000269|PubMed:10979956, ECO:0000269|PubMed:11085985, ECO:0000269|PubMed:11278976, ECO:0000269|PubMed:11782313, ECO:0000269|PubMed:14729465, ECO:0000269|PubMed:15642749, ECO:0000269|PubMed:16103226, ECO:0000269|PubMed:16129829, ECO:0000269|PubMed:16236794, ECO:0000269|PubMed:19468300, ECO:0000269|PubMed:19468302, ECO:0000269|PubMed:23235882, ECO:0000269|PubMed:9497316}.;
- Pathway
- Signal Transduction of S1P Receptor;Wnt Signaling Pathway and Pluripotency;Signal Transduction;Vesicle-mediated transport;Membrane Trafficking;Kinesins;Factors involved in megakaryocyte development and platelet production;Rho GTPase cycle;Signaling by Rho GTPases;EGFR1;Regulation of RAC1 activity;Hemostasis;COPI-dependent Golgi-to-ER retrograde traffic;Golgi-to-ER retrograde transport;Regulation of CDC42 activity;RAC1 signaling pathway;Aurora B signaling;Intra-Golgi and retrograde Golgi-to-ER traffic
(Consensus)
Recessive Scores
- pRec
- 0.159
Intolerance Scores
- loftool
- 0.472
- rvis_EVS
- -0.4
- rvis_percentile_EVS
- 26.73
Haploinsufficiency Scores
- pHI
- 0.331
- hipred
- Y
- hipred_score
- 0.742
- ghis
- 0.702
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.781
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Racgap1
- Phenotype
- immune system phenotype; 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;
Zebrafish Information Network
- Gene name
- racgap1
- Affected structure
- neutrophil
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- mitotic cytokinesis;actomyosin contractile ring assembly;retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum;microtubule-based movement;spermatogenesis;neuroblast proliferation;sulfate transport;antigen processing and presentation of exogenous peptide antigen via MHC class II;positive regulation of cytokinesis;intracellular signal transduction;positive regulation of GTPase activity;regulation of embryonic development;regulation of small GTPase mediated signal transduction;mitotic spindle midzone assembly;regulation of attachment of spindle microtubules to kinetochore
- Cellular component
- acrosomal vesicle;nucleus;nucleoplasm;cytosol;microtubule;midbody;extrinsic component of cytoplasmic side of plasma membrane;cleavage furrow;spindle midzone;extracellular exosome;mitotic spindle;Flemming body;centralspindlin complex
- Molecular function
- GTPase activator activity;protein binding;phosphatidylinositol-3,4,5-trisphosphate binding;microtubule binding;protein kinase binding;alpha-tubulin binding;gamma-tubulin binding;metal ion binding;beta-tubulin binding