JAGN1

Last update 08 May 2025

Basic Info

Synonyms

FLJ14602, GL009, JAGN1

+ [2]

Introduction

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.

100 Clinical Results associated with JAGN1

100 Translational Medicine associated with JAGN1

0 Patents (Medical) associated with JAGN1

Literatures (Medical) associated with JAGN1

08 Apr 2025·Blood Advances

Extended clinical phenotypes and treatment modalities in 32 JAGN1-deficient patients: a multicenter study by ESID and EBMT IEWP

Article

Author: Gonzalez-Granado, Luis Ignacio ; Sharafian, Samin ; Bakhtiar, Shahrzad ; Finocchi, Andrea ; Baris, Safa ; Bader, Peter ; Albert, Michael H. ; Seidel, Markus ; Zeidler, Cornelia ; Beaupain, Blandine ; Fekadu-Siebald, Julia ; Bellanné-Chantelot, Christine ; Sherkat, Roya ; Kindle, Gerhard ; Klaudel-Dreszler, Maja ; Algeri, Mattia ; Chavoshzadeh, Zahra ; Heusel, Jan Robert ; Donadieu, Jean ; Willasch, Andre ; Salzmann-Manrique, Emilia ; Cuntz, Franziska ; Hauck, Fabian ; Paillard, Catherine ; Neven, Bénédicte

AbstractJagunal-homolog1 (JAGN1) is an endoplasmic reticulum–resident protein, which is part of the early secretory pathway and granulocyte colony-stimulating factor (CSF; G-CSF) receptor–mediated signaling. Autosomal recessively inherited variants in JAGN1 lead to congenital neutropenia, early-onset bacterial infections, aphthosis, and skin abscesses due to aberrant differentiation and maturation of neutrophils. Bone metabolism disorders and syndromic phenotype, including facial features, short stature, and neurodevelopmental delay, have been reported. Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a treatment option for patients who respond poorly to therapy with G-CSF and those who suffer from complicated infections. In a retrospective multicenter study, data from 32 patients with JAGN1 deficiency were collected to describe the disease, perform phenotype-genotype analysis, and evaluate treatment modalities. Patients presented with 9 homozygous mutations in JAGN1. All patients experienced infectious complications. Twelve patients presented with short stature and facial features. Neurodevelopmental delay was observed in 4 patients from 3 families. Variant c.3G>A p.Met1, found in 9 patients, was never connected to extramedullary symptoms, except for short stature in 1 patient. Patients with the variants c.63G>T, p.Glu21Asp and c130c>T p.His44 Tyr presented more often with syndromic facial features and bone metabolism disorders. Six patients underwent allogeneic stem cell transplantation due to therapy-refractory neutropenia and severe infections, 1 received the graft because of myelodysplastic syndrome and secondary acute myeloid leukemia. Two patients had to undergo a second transplantation because of autologous reconstitution. One patient who did not undergo transplantation died at age 5 years due to pancolitis and septicemia. All 31 other patients were alive and healthy at the last follow-up.

01 Sep 2024·Journal of Clinical Pathology

Discerning clinicopathological features of congenital neutropenia syndromes: an approach to diagnostically challenging differential diagnoses

Review

Author: Parisi, Xenia ; Bledsoe, Jacob R

The congenital neutropenia syndromes are rare haematological conditions defined by impaired myeloid precursor differentiation or function. Patients are prone to severe infections with high mortality rates in early life. While some patients benefit from granulocyte colony-stimulating factor treatment, they may still face an increased risk of bone marrow failure, myelodysplastic syndrome and acute leukaemia. Accurate diagnosis is crucial for improved outcomes; however, diagnosis depends on familiarity with a heterogeneous group of rare disorders that remain incompletely characterised. The clinical and pathological overlap between reactive conditions, primary and congenital neutropenias, bone marrow failure, and myelodysplastic syndromes further clouds diagnostic clarity.We review the diagnostically useful clinicopathological and morphological features of reactive causes of neutropenia and the most common primary neutropenia disorders: constitutional/benign ethnic neutropenia, chronic idiopathic neutropenia, cyclic neutropenia, severe congenital neutropenia (due to mutations inELANE,GFI1,HAX1,G6PC3,VPS45,JAGN1,CSF3R,SRP54,CLPBandWAS), GATA2 deficiency, Warts, hypogammaglobulinaemia, infections and myelokathexis syndrome, Shwachman-Diamond Syndrome, the lysosomal storage disorders with neutropenia: Chediak-Higashi, Hermansky-Pudlak, and Griscelli syndromes, Cohen, and Barth syndromes. We also detail characteristic cytogenetic and molecular factors at diagnosis and in progression to myelodysplastic syndrome/leukaemia.

13 Aug 2024·Blood Advances

A JAGN1-associated severe congenital neutropenia zebrafish model revealed an altered G-CSFR signaling and UPR activation

Article

Author: Welte, Karl ; Doll, Larissa ; Bajoghli, Baubak ; Skokowa, Julia

AbstractA variety of autosomal recessive mutations in the JAGN1 gene cause severe congenital neutropenia (CN). However, the underlying pathomechanism remains poorly understood, mainly because of the limited availability of primary hematopoietic stem cells from JAGN1-CN patients and the absence of animal models. In this study, we aimed to address these limitations by establishing a zebrafish model of JAGN1-CN. We found 2 paralogs of the human JAGN1 gene, namely jagn1a and jagn1b, which play distinct roles during zebrafish hematopoiesis. Using various approaches such as morpholino-based knockdown, CRISPR/Cas9–based gene editing, and misexpression of a jagn1b harboring a specific human mutation, we successfully developed neutropenia while leaving other hematopoietic lineages unaffected. Further analysis of our model revealed significant upregulation of apoptosis and genes involved in the unfolded protein response (UPR). However, neither UPR nor apoptosis is the primary mechanism that leads to neutropenia in zebrafish. Instead, Jagn1b has a critical role in granulocyte colony-stimulating factor receptor signaling and steady-state granulopoiesis, shedding light on the pathogenesis of neutropenia associated with JAGN1 mutations. The establishment of a zebrafish model for JAGN1-CN represents a significant advancement in understanding the specific pathologic pathways underlying the disease. This model provides a valuable in vivo tool for further investigation and exploration of potential therapeutic strategies.

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JAGN1

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