JAGN1
Basic information
Region (hg38): 3:9890574-9894349
Links
Phenotypes
GenCC
Source:
- autosomal recessive severe congenital neutropenia due to JAGN1 deficiency (Strong), mode of inheritance: AR
- autosomal recessive severe congenital neutropenia due to JAGN1 deficiency (Supportive), mode of inheritance: AR
- autosomal recessive severe congenital neutropenia due to JAGN1 deficiency (Definitive), mode of inheritance: AR
Clinical Genomic Database
Source:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Neutropenia, severe congenital, 6, autosomal recessive | AR | Allergy/Immunology/Infectious | Individuals may sufffer from severe, recurrent bacterial infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; BMT has been reported | Allergy/Immunology/Infectious | 25129144 |
ClinVar
This is a list of variants' phenotypes submitted to
- Autosomal_recessive_severe_congenital_neutropenia_due_to_JAGN1_deficiency (124 variants)
- Inborn_genetic_diseases (24 variants)
- not_provided (15 variants)
- Severe_congenital_neutropenia (8 variants)
- JAGN1-related_disorder (4 variants)
- Frontotemporal_dementia_and/or_amyotrophic_lateral_sclerosis_7 (1 variants)
- not_specified (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the JAGN1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000032492.4. 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 | 37 | 41 | ||||
missense | 67 | 75 | ||||
nonsense | 3 | |||||
start loss | 1 | 1 | 2 | |||
frameshift | 6 | |||||
splice donor/acceptor (+/-2bp) | 1 | |||||
Total | 2 | 7 | 74 | 40 | 5 |
Highest pathogenic variant AF is 0.0000186618
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
JAGN1 | protein_coding | protein_coding | ENST00000307768 | 2 | 3796 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
0.00745 | 0.789 | 125728 | 0 | 19 | 125747 | 0.0000756 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 0.0582 | 103 | 105 | 0.984 | 0.00000557 | 1191 |
Missense in Polyphen | 20 | 24.081 | 0.83053 | 289 | ||
Synonymous | -0.844 | 49 | 42.0 | 1.17 | 0.00000232 | 362 |
Loss of Function | 0.973 | 4 | 6.72 | 0.595 | 2.90e-7 | 75 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.000325 | 0.000325 |
Ashkenazi Jewish | 0.000298 | 0.000298 |
East Asian | 0.00 | 0.00 |
Finnish | 0.0000462 | 0.0000462 |
European (Non-Finnish) | 0.0000264 | 0.0000264 |
Middle Eastern | 0.00 | 0.00 |
South Asian | 0.0000980 | 0.0000980 |
Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Endoplasmic reticulum transmembrane protein involved in vesicle-mediated transport, which is required for neutrophil function. Required for vesicle-mediated transport; it is however unclear whether it is involved in early secretory pathway or intracellular protein transport. Acts as a regulator of neutrophil function, probably via its role in vesicle-mediated transport: required for defense against fungal pathogens and for granulocyte colony-stimulating factor (GM-CSF) signaling pathway; possibly by regulating glycosylation and/or targeting of proteins contributing to the viability and migration of neutrophils. {ECO:0000269|PubMed:25129144, ECO:0000305}.;
Intolerance Scores
- loftool
- 0.383
- rvis_EVS
- 0.15
- rvis_percentile_EVS
- 64.32
Haploinsufficiency Scores
- pHI
- 0.0684
- hipred
- N
- hipred_score
- 0.253
- ghis
- 0.505
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.259
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Jagn1
- Phenotype
- hematopoietic system phenotype; immune system phenotype; cellular phenotype;
Gene ontology
- Biological process
- neutrophil mediated immunity;exocytosis;endoplasmic reticulum organization;protein transport;vesicle-mediated transport;neutrophil differentiation;granulocyte colony-stimulating factor signaling pathway;defense response to fungus;negative regulation of insulin secretion involved in cellular response to glucose stimulus;cellular response to tunicamycin;neutrophil migration
- Cellular component
- endoplasmic reticulum;endoplasmic reticulum membrane;integral component of membrane
- Molecular function
- protein binding