GBF1
golgi brefeldin A resistant guanine nucleotide exchange factor 1, the group of Sec7 family
Basic information
Region (hg38): 10:102245371-102382899
Links
Phenotypes
GenCC
Source:
- axonal neuropathy (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Charcot-Marie-Tooth disease, axonal, type 2GG | AD | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Neurologic | 32937143 |
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 GBF1 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 | 4 | |||||
| missense | 81 | 83 | ||||
| nonsense | 2 | |||||
| start loss | 0 | |||||
| frameshift | 1 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 1 | 1 | ||||
| non coding | 1 | |||||
| Total | 0 | 1 | 84 | 2 | 4 |
Variants in GBF1
This is a list of pathogenic ClinVar variants found in the GBF1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 10-102259006-A-G | not specified | Uncertain significance (May 26, 2024) | ||
| 10-102259011-C-T | Uncertain significance (Nov 30, 2021) | |||
| 10-102259012-G-A | not specified | Uncertain significance (Nov 14, 2024) | ||
| 10-102259021-C-G | not specified | Uncertain significance (May 23, 2023) | ||
| 10-102260059-C-T | not specified | Uncertain significance (Aug 14, 2024) | ||
| 10-102344105-G-T | Uncertain significance (Mar 02, 2022) | |||
| 10-102351274-C-T | not specified | Uncertain significance (Jan 26, 2022) | ||
| 10-102351900-T-C | not specified | Uncertain significance (Dec 04, 2024) | ||
| 10-102352451-T-C | Benign (Apr 04, 2018) | |||
| 10-102352490-G-C | Charcot-Marie-Tooth disease, dominant intermediate A;Charcot-Marie-Tooth Disease, axonal, type 2GG | Uncertain significance (Jan 04, 2024) | ||
| 10-102352496-A-G | not specified • Charcot-Marie-Tooth Disease, axonal, type 2GG | Uncertain significance (Dec 19, 2024) | ||
| 10-102358083-G-T | not specified | Uncertain significance (Jan 02, 2024) | ||
| 10-102358106-C-T | not specified | Uncertain significance (Mar 18, 2024) | ||
| 10-102358112-G-A | not specified | Uncertain significance (Dec 19, 2023) | ||
| 10-102358118-T-C | Benign (Nov 01, 2024) | |||
| 10-102358124-A-G | not specified | Uncertain significance (Aug 01, 2024) | ||
| 10-102358157-A-G | not specified | Uncertain significance (Jun 13, 2024) | ||
| 10-102358163-C-T | not specified | Uncertain significance (May 11, 2022) | ||
| 10-102358542-C-T | not specified | Uncertain significance (Jan 27, 2022) | ||
| 10-102358608-C-T | not specified | Uncertain significance (Dec 19, 2023) | ||
| 10-102358641-A-G | not specified | Uncertain significance (May 10, 2024) | ||
| 10-102358676-G-T | not specified | Uncertain significance (Jun 16, 2022) | ||
| 10-102358677-C-A | not specified | Uncertain significance (Jun 16, 2022) | ||
| 10-102358709-C-T | GBF1-related disorder | Uncertain significance (Jun 18, 2024) | ||
| 10-102358724-C-T | not specified | Uncertain significance (Nov 18, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| GBF1 | protein_coding | protein_coding | ENST00000369983 | 39 | 137368 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 4.75e-15 | 1.00 | 125675 | 0 | 73 | 125748 | 0.000290 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.41 | 844 | 1.07e+3 | 0.792 | 0.0000622 | 12137 |
| Missense in Polyphen | 226 | 359.08 | 0.62939 | 4116 | ||
| Synonymous | -0.142 | 413 | 409 | 1.01 | 0.0000228 | 3786 |
| Loss of Function | 5.28 | 42 | 98.6 | 0.426 | 0.00000599 | 1041 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000412 | 0.000412 |
| Ashkenazi Jewish | 0.000198 | 0.000198 |
| East Asian | 0.000272 | 0.000272 |
| Finnish | 0.000185 | 0.000185 |
| European (Non-Finnish) | 0.000354 | 0.000352 |
| Middle Eastern | 0.000272 | 0.000272 |
| South Asian | 0.000229 | 0.000229 |
| Other | 0.000493 | 0.000489 |
dbNSFP
Source:
- Function
- FUNCTION: Guanine-nucleotide exchange factor (GEF) for members of the Arf family of small GTPases involved in trafficking in the early secretory pathway; its GEF activity initiates the coating of nascent vesicles via the localized generation of activated ARFs through replacement of GDP with GTP. Recruitment to cis-Golgi membranes requires membrane association of Arf-GDP and can be regulated by ARF1, ARF3, ARF4 and ARF5. Involved in the recruitment of the COPI coat complex to the endoplasmic reticulum exit sites (ERES), and the endoplasmic reticulum-Golgi intermediate (ERGIC) and cis-Golgi compartments which implicates ARF1 activation. Involved in COPI vesicle-dependent retrograde transport from the ERGIC and cis-Golgi compartments to the endoplasmic reticulum (ER) (PubMed:16926190, PubMed:17956946, PubMed:18003980, PubMed:12047556, PubMed:12808027, PubMed:19039328, PubMed:24213530). Involved in the trans-Golgi network recruitment of GGA1, GGA2, GGA3, BIG1, BIG2, and the AP-1 adaptor protein complex related to chlathrin-dependent transport; the function requires its GEF activity (probably at least in part on ARF4 and ARF5) (PubMed:23386609). Has GEF activity towards ARF1 (PubMed:15616190). Has in vitro GEF activity towards ARF5 (By similarity). Involved in the processing of PSAP (PubMed:17666033). Required for the assembly of the Golgi apparatus (PubMed:12808027, PubMed:18003980). The AMPK-phosphorylated form is involved in Golgi disassembly during mitotis and under stress conditions (PubMed:18063581, PubMed:23418352). May be involved in the COPI vesicle-dependent recruitment of PNPLA2 to lipid droplets; however, this function is under debate (PubMed:19461073, PubMed:22185782). In neutrophils, involved in G protein-coupled receptor (GPCR)-mediated chemotaxis und superoxide production. Proposed to be recruited by phosphatidylinositol-phosphates generated upon GPCR stimulation to the leading edge where it recruits and activates ARF1, and is involved in recruitment of GIT2 and the NADPH oxidase complex (PubMed:22573891). {ECO:0000250|UniProtKB:Q9R1D7, ECO:0000269|PubMed:12047556, ECO:0000269|PubMed:12808027, ECO:0000269|PubMed:15616190, ECO:0000269|PubMed:16926190, ECO:0000269|PubMed:17666033, ECO:0000269|PubMed:17956946, ECO:0000269|PubMed:18003980, ECO:0000269|PubMed:18063581, ECO:0000269|PubMed:19461073, ECO:0000269|PubMed:22185782, ECO:0000269|PubMed:22573891, ECO:0000269|PubMed:23386609, ECO:0000269|PubMed:23418352, ECO:0000269|PubMed:24213530, ECO:0000305|PubMed:19039328, ECO:0000305|PubMed:22573891}.;
- Pathway
- Endocytosis - Homo sapiens (human);Clathrin derived vesicle budding;trans-Golgi Network Vesicle Budding;Vesicle-mediated transport;thrombin signaling and protease-activated receptors;Membrane Trafficking;Post-translational protein modification;Metabolism of proteins;adp-ribosylation factor;Transport to the Golgi and subsequent modification;Asparagine N-linked glycosylation;Arf1 pathway;COPI-dependent Golgi-to-ER retrograde traffic;Golgi-to-ER retrograde transport;COPI-mediated anterograde transport;ER to Golgi Anterograde Transport;VxPx cargo-targeting to cilium;Cargo trafficking to the periciliary membrane;Intra-Golgi and retrograde Golgi-to-ER traffic;Cilium Assembly;Organelle biogenesis and maintenance
(Consensus)
Recessive Scores
- pRec
- 0.105
Intolerance Scores
- loftool
- 0.723
- rvis_EVS
- -3
- rvis_percentile_EVS
- 0.54
Haploinsufficiency Scores
- pHI
- 0.652
- hipred
- Y
- hipred_score
- 0.611
- ghis
- 0.627
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.877
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Gbf1
- Phenotype
- skeleton 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);
Zebrafish Information Network
- Gene name
- gbf1
- Affected structure
- vasculature
- Phenotype tag
- abnormal
- Phenotype quality
- hemorrhagic
Gene ontology
- Biological process
- cell activation involved in immune response;endoplasmic reticulum to Golgi vesicle-mediated transport;retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum;post-Golgi vesicle-mediated transport;Golgi to endosome transport;Golgi organization;regulation of mitotic cell cycle;protein transport;viral process;neutrophil chemotaxis;regulation of ARF protein signal transduction;protein localization to Golgi apparatus;retrograde transport, endosome to Golgi;COPI coating of Golgi vesicle;establishment of monopolar cell polarity;protein localization to endoplasmic reticulum exit site;Golgi disassembly;endoplasmic reticulum-Golgi intermediate compartment organization;cellular response to virus;reactive oxygen species biosynthetic process;protein localization to endoplasmic reticulum tubular network;regulation of protein localization to cell surface
- Cellular component
- Golgi membrane;mitochondrion;peroxisome;endoplasmic reticulum lumen;endoplasmic reticulum-Golgi intermediate compartment;Golgi apparatus;Golgi stack;cis-Golgi network;trans-Golgi network;lipid droplet;cytosol;membrane;cell leading edge
- Molecular function
- guanyl-nucleotide exchange factor activity;ARF guanyl-nucleotide exchange factor activity;protein binding;phosphatidylinositol-3,4,5-trisphosphate binding;phosphatidylinositol-3,5-bisphosphate binding