Ask about this productRelated genes to: LMAN1 antibody
- Gene:
- LMAN1 NIH gene
- Name:
- lectin, mannose binding 1
- Previous symbol:
- F5F8D
- Synonyms:
- MR60, ERGIC-53, ERGIC53, gp58, MCFD1, FMFD1
- Chromosome:
- 18q21.32
- Locus Type:
- gene with protein product
- Date approved:
- 1996-06-06
- Date modifiied:
- 2019-04-23
- Gene:
- MCFD2 NIH gene
- Name:
- multiple coagulation factor deficiency 2
- Previous symbol:
- -
- Synonyms:
- F5F8D, LMAN1IP, SDNSF
- Chromosome:
- 2p21
- Locus Type:
- gene with protein product
- Date approved:
- 2003-06-24
- Date modifiied:
- 2019-04-23
Related products to: LMAN1 antibody
Related articles to: LMAN1 antibody
- We present a case of a patient who was found to have incidental deficiencies of combined factor V (F5) and factor VIII (F8) identified on pre-operative screening. Our patient is a 61-year-old male with a past medical history of hyperparathyroidism, hypercalcemia, and mild kidney dysfunction. He was referred to the hematology clinic as he was found to have an abnormal activated partial thromboplastin time (aPTT) while being evaluated preoperatively for a parathyroidectomy. The patient did not have any significant history of bleeding, bruising, or hemarthrosis but recalls occasional nosebleeds in childhood. The patient was screened with PT/aPTT by his primary care prior to surgery. This revealed a mildly prolonged aPTT and a normal prothrombin time (PT), and the patient was referred to hematology. Further studies one week later revealed decreased F5 and F8 activity. von Willebrand Factor antigen levels were normal. CBC, protein C and S activity, and antiphospholipid antibody screening were normal as well. This is postulated to arise from a monogenic mechanism, classically through biallelic variants in LMAN1 or MCFD2, leading to combined F5 and F8 deficiency. Rarely, it can be of digenic inheritance with separate defects in F5 and F8. We outline considerations for perioperative evaluation and family counseling in the setting of a rare coagulopathy. - Source: PubMed
Publication date: 2025/09/01
Luzarraga Joseph LPurow Jeremy IBerkman Aron - Factor VIII (FVIII) interacts with Endoplasmic Reticulum (ER) chaperones Calnexin (CANX) and Calreticulin (CALR) and with ER-Golgi Intermediate Compartment (ERGIC) transporters, Lectin, mannose-binding 1 (LMAN1) and Multiple Coagulation Deficiency 2 (MCFD2). We previously reported that the Gamma-aminobutyric Acid Receptor-associated proteins (GABARAPs) also influence FVIII secretion. Here, we further investigated the intracellular dynamics of FVIII using single and double CRISPR/Cas9 Knockout (KO) models of the abovementioned chaperones as well as the GABARAP proteins in HEK293 cells expressing FVIII. Cellular pathways were manipulated by Brefeldin A (BFA), Chloroquine (CQ), a Rab7 inhibitor, and subjected to glucose starvation. The effect of each KO on FVIII secretion and organelle distribution was assessed by a two-stage chromogenic assay and immunofluorescence (IF) microscopy, prior and upon cell treatments. Using these approaches, we first observed distinct effects of each studied protein on FVIII trafficking. Notably, intracellular localization patterns revealed clustering of FVIII phenotypes in GABARAP, CANX, and CALR cells together under both basal and treated conditions, an observation that was also reflected in their respective double KO combinations. Besides, a clear involvement of additional components of the endomembrane system was evident, specifically at the -Golgi space, as marked by FVIII colocalization with the Ras-like proteins in brain (Rab8 and Rab7) and with the Vesicle-Associated Membrane Protein (VAMP8), along with the observed impact of the selected cell treatments on FVIII phenotypes. These outcomes enhance our understanding of the molecular mechanisms regulating FVIII and pave the way for new perspectives, which could be further projected into FVIII replacement, cell and gene therapies. - Source: PubMed
Publication date: 2025/07/01
El Hazzouri SalimeAl-Rifai RawyaSurges NicoleRath MelanieSinger HeikeOldenburg JohannesEl-Maarri Osman - Combined deficiency of factors V and VIII is a rare autosomal recessive disorder associated with an increased risk of bleeding. We present an unusual case of a 7-year-old Moroccan child with no history of consanguinity who was hospitalized owing to a hemorrhagic episode during circumcision. - Source: PubMed
Publication date: 2025/04/28
Bendarkawi YasmineMamad HassaneBerchane ZakiaBenkirane SouadMasrar Azlarab - Thrombopoietin (TPO) is a plasma glycoprotein that binds its receptor on megakaryocytes (MKs) and MK progenitors, resulting in enhanced platelet production. The mechanism by which TPO is secreted from hepatocytes remains poorly understood. Lectin mannose-binding 1 (LMAN1) and multiple coagulation factor deficiency 2 (MCFD2) form a complex at the endoplasmic reticulum membrane, recruiting cargo proteins into COPII vesicles for secretion. In this study, we showed that LMAN1-deficient mice (with complete germline LMAN1 deficiency) exhibited mild thrombocytopenia, whereas the platelet count was entirely normal in mice with approximately 7% Lman1 expression. Surprisingly, mice deleted for Mcfd2 did not exhibit thrombocytopenia. Analysis of peripheral blood from LMAN1-deficient mice demonstrated normal platelet size and normal morphology of dense and alpha granules. LMAN1-deficient mice exhibited a trend toward reduced MK and MK progenitors in the bone marrow. We next showed that hepatocyte-specific but not hematopoietic Lman1 deletion results in thrombocytopenia, with plasma TPO level reduced in LMAN1-deficient mice, despite normal Tpo mRNA levels in LMAN1-deficient livers. TPO and LMAN1 interacted by coimmunoprecipitation in a heterologous cell line, and TPO accumulated intracellularly in LMAN1-deleted cells. Together, these studies verified the hepatocyte as the cell of origin for TPO production in vivo and were consistent with LMAN1 as the endoplasmic reticulum cargo receptor that mediates the efficient secretion of TPO. To our knowledge, TPO is the first example of an LMAN1-dependent cargo that is independent of MCFD2. - Source: PubMed
Publication date: 2024/12/20
Everett Lesley ALin ZesenFriedman AnnTang Vi TMyers GreggoryBalbin-Cuesta GinetteKing RichardZhu GuojingMcGee BethKhoriaty Rami - Combined deficiency of coagulation factor V (FV) and factor VIII (FVIII) is a rare bleeding disease caused by variants in either lectin mannose binding 1 (LMAN1) or multiple coagulation factor deficiency 2 (MCFD2) gene. Reducing the level of FVIII by inhibiting the LMAN1-MCFD2 complex may become a new anticoagulant approach. We aimed to find a new therapeutic option for anticoagulation by RNA interference (RNAi) targeting LMAN1 and MCFD2. siRNA sequences with cross-homology between mice and humans were designed based on LMAN1 or MCFD2 transcripts in NCBI and were screened with the Dual-Luciferase reporter assay. The optimal siRNAs were chemically modified and conjugated with three N-acetylgalactosamine molecules (GalNAc-siRNA), promoting their targeted delivery to the liver. The expression of LMAN1 and MCFD2 in cell lines or mice was examined by RT-qPCR and western blotting. For the mice administered with siRNA, we assessed their coagulation function by measuring APTT and the activity of FVIII factor. After administration, siRNAs GalNAc-LMAN1 and GalNAc-MCFD2 demonstrated effective and persistent LMAN1 and MCFD2 inhibition. 7 days after injection of 3mg/kg GalNAc-LMAN1, the LMAN1 mRNA levels reduced to 19.97% ± 3.78%. MCFD2 mRNA levels reduced to 32.22% ± 13.14% with injection of 3mg/kg GalNAc-MCFD2. After repeated administration, APTT was prolonged and the FVIII activity was remarkably decreased. The tail bleeding test of mice showed that the amount of bleeding in the treated group did not significantly increase compared with the control group. Our study confirms that therapy with RNAi targeting LMAN1-MCFD2 complex is effective and can be considered a viable option for anticoagulation drugs. However, the benefits and potential risk of bleeding in thrombophilic mice model needs to be evaluated. - Source: PubMed
Publication date: 2024/09/02
Ma SiqianLiu BoyanDu HongYang FeiHan JingjingHuang XinqiZhang MinyangJi ShundongJiang Miao