ARFGEF1
Basic information
Region (hg38): 8:67173511-67343781
Links
Phenotypes
GenCC
Source:
- schizophrenia (Limited), mode of inheritance: Unknown
- developmental delay, impaired speech, and behavioral abnormalities, with or without seizures (Strong), mode of inheritance: AD
- developmental delay, impaired speech, and behavioral abnormalities, with or without seizures (Definitive), mode of inheritance: AD
- developmental delay, impaired speech, and behavioral abnormalities, with or without seizures (Strong), mode of inheritance: AD
- developmental delay, impaired speech, and behavioral abnormalities, with or without seizures (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Developmental delay, impaired speech, and behavioral abnormalities, with or without seizures | 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 | Craniofacial; Neurologic; Ophthalmologic | 31678406; 34113008 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (152 variants)
- Inborn_genetic_diseases (119 variants)
- Developmental_delay,_impaired_speech,_and_behavioral_abnormalities,_with_or_without_seizures (69 variants)
- ARFGEF1-related_disorder (17 variants)
- not_specified (11 variants)
- Global_developmental_delay (10 variants)
- Intellectual_disability (10 variants)
- Delayed_speech_and_language_development (10 variants)
- Atypical_behavior (9 variants)
- Neurodevelopmental_delay (4 variants)
- DEVELOPMENTAL_DELAY,_IMPAIRED_SPEECH,_BEHAVIORAL_ABNORMALITIES,_AND_SEIZURES (3 variants)
- Neurodevelopmental_disorder (2 variants)
- Seizure (2 variants)
- Developmental_delay,_impaired_speech,_and_behavioral_abnormalities (1 variants)
- See_cases (1 variants)
- Focal-onset_seizure (1 variants)
- Delayed_ability_to_walk (1 variants)
- Developmental_disorder (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the ARFGEF1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000006421.5. 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 | 12 | 19 | ||||
missense | 240 | 19 | 265 | |||
nonsense | 14 | 24 | ||||
start loss | 0 | |||||
frameshift | 12 | 24 | ||||
splice donor/acceptor (+/-2bp) | 18 | |||||
Total | 31 | 28 | 254 | 31 | 6 |
Highest pathogenic variant AF is 0.000006866
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
ARFGEF1 | protein_coding | protein_coding | ENST00000262215 | 39 | 170166 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
1.00 | 3.70e-11 | 125662 | 0 | 86 | 125748 | 0.000342 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 5.37 | 479 | 943 | 0.508 | 0.0000464 | 12216 |
Missense in Polyphen | 118 | 383.68 | 0.30755 | 5103 | ||
Synonymous | -0.378 | 334 | 325 | 1.03 | 0.0000163 | 3401 |
Loss of Function | 8.58 | 8 | 101 | 0.0792 | 0.00000530 | 1237 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.000436 | 0.000430 |
Ashkenazi Jewish | 0.00 | 0.00 |
East Asian | 0.00280 | 0.00261 |
Finnish | 0.000139 | 0.000139 |
European (Non-Finnish) | 0.0000814 | 0.0000791 |
Middle Eastern | 0.00280 | 0.00261 |
South Asian | 0.000527 | 0.000457 |
Other | 0.000528 | 0.000489 |
dbNSFP
Source:
- Function
- FUNCTION: Promotes guanine-nucleotide exchange on ARF1 and ARF3. Promotes the activation of ARF1/ARF3 through replacement of GDP with GTP. Involved in vesicular trafficking. Required for the maintenance of Golgi structure; the function may be independent of its GEF activity. Required for the maturaion of integrin beta-1 in the Golgi. Involved in the establishment and persistence of cell polarity during directed cell movement in wound healing. Proposed to act as A kinase-anchoring protein (AKAP) and may mediate crosstalk between Arf and PKA pathways. Inhibits GAP activity of MYO9B probably through competetive RhoA binding. The function in the nucleus remains to be determined. {ECO:0000269|PubMed:12571360, ECO:0000269|PubMed:15644318, ECO:0000269|PubMed:17227842, ECO:0000269|PubMed:20360857, ECO:0000269|PubMed:22084092}.;
- Pathway
- Endocytosis - Homo sapiens (human);thrombin signaling and protease-activated receptors;adp-ribosylation factor
(Consensus)
Recessive Scores
- pRec
- 0.283
Intolerance Scores
- loftool
- 0.444
- rvis_EVS
- -1.75
- rvis_percentile_EVS
- 2.37
Haploinsufficiency Scores
- pHI
- 0.899
- hipred
- Y
- hipred_score
- 0.736
- ghis
- 0.657
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.839
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Arfgef1
- Phenotype
- cellular 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); 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);
Gene ontology
- Biological process
- exocytosis;Golgi organization;endomembrane system organization;protein transport;vesicle-mediated transport;negative regulation of actin filament polymerization;neuron projection development;regulation of ARF protein signal transduction;negative regulation of GTPase activity;positive regulation of GTPase activity;positive regulation of protein kinase B signaling;positive regulation of protein glycosylation in Golgi;positive regulation of wound healing;regulation of establishment of cell polarity
- Cellular component
- Golgi membrane;nucleoplasm;nucleolus;Golgi apparatus;trans-Golgi network;cytosol;nuclear matrix;small nuclear ribonucleoprotein complex;perinuclear region of cytoplasm
- Molecular function
- guanyl-nucleotide exchange factor activity;ARF guanyl-nucleotide exchange factor activity;GTPase activator activity;protein binding;myosin binding;protein kinase A regulatory subunit binding