JAGN1

jagunal homolog 1

Basic information

Region (hg38): 3:9890574-9894349

Links

ENSG00000171135 ∙ NCBI:84522 ∙ OMIM:616012 ∙ HGNC:26926 ∙ Uniprot:Q8N5M9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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: CGD

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 ClinVar and linked to the JAGN1 gene.

• 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				37	4	41
missense	1	4	67	2	1	75
nonsense	1	1	1			3
start loss		1		1		2
frameshift		1	5			6
splice donor/acceptor (+/-2bp)			1			1
Total	2	7	74	40	5

Highest pathogenic variant AF is 0.0000186618

GnomAD

Source: gnomAD

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: dbNSFP

• 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