ARFGEF1

ADP ribosylation factor guanine nucleotide exchange factor 1, the group of Armadillo like helical domain containing|ARFGEF family

Basic information

Region (hg38): 8:67173511-67343781

Links

ENSG00000066777NCBI:10565OMIM:604141HGNC:15772Uniprot:Q9Y6D6AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • 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: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Developmental delay, impaired speech, and behavioral abnormalities, with or without seizuresADGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingCraniofacial; Neurologic; Ophthalmologic31678406; 34113008

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ARFGEF1 gene.

  • 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.

EffectPLPVUSLBBSum
synonymous
2
clinvar
12
clinvar
5
clinvar
19
missense
1
clinvar
4
clinvar
240
clinvar
19
clinvar
1
clinvar
265
nonsense
14
clinvar
7
clinvar
3
clinvar
24
start loss
0
frameshift
12
clinvar
8
clinvar
4
clinvar
24
splice donor/acceptor (+/-2bp)
4
clinvar
9
clinvar
5
clinvar
18
Total 31 28 254 31 6

Highest pathogenic variant AF is 0.000006866

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
ARFGEF1protein_codingprotein_codingENST00000262215 39170166
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
1.003.70e-111256620861257480.000342
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense5.374799430.5080.000046412216
Missense in Polyphen118383.680.307555103
Synonymous-0.3783343251.030.00001633401
Loss of Function8.5881010.07920.000005301237

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0004360.000430
Ashkenazi Jewish0.000.00
East Asian0.002800.00261
Finnish0.0001390.000139
European (Non-Finnish)0.00008140.0000791
Middle Eastern0.002800.00261
South Asian0.0005270.000457
Other0.0005280.000489

dbNSFP

Source: dbNSFP

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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