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LMAN1
lectin, mannose binding 1
LMAN1 is located on the long (q) arm of chromosome 18, at band 18q21.32. Arm ratio per GRCh38 - banding schematic.
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Overview
LMAN1 (lectin, mannose binding 1) is located on chromosome 18 and encodes a transmembrane protein that resides in the endoplasmic reticulum-Golgi intermediate compartment. The protein functions as a quality-control checkpoint, selectively binding glycoproteins that bear specific mannose-rich carbohydrate structures and escorting them through the secretory pathway.
This cargo-receptor function is particularly important for the proper secretion of clotting factors and other proteins destined for release from the cell. Pathogenic variants in LMAN1 can disrupt this transport mechanism, leading to reduced levels of specific proteins in the bloodstream even when those proteins are synthesised normally.
What the gene does
The LMAN1 protein operates as a lectin, meaning it binds to carbohydrate structures rather than peptide sequences. It recognises high-mannose glycans on newly synthesised glycoproteins within the endoplasmic reticulum, distinguishing cargo proteins that are ready for export from those still undergoing folding and modification.
Once bound to cargo, LMAN1 facilitates the packaging of these proteins into transport vesicles that bud from the endoplasmic reticulum and deliver their contents to the Golgi apparatus. This selective transport process ensures that only properly folded and modified proteins advance through the secretory pathway, whilst incompletely processed proteins are retained for further modification or degradation.
The protein works in cooperation with another cargo receptor, MCFD2, to form a functional complex. This partnership is particularly critical for the efficient secretion of coagulation factors V and VIII, which are essential components of the blood clotting cascade.
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Chromosome location
LMAN1 is positioned at chromosomal band 18q21.32 on the long arm of chromosome 18. The gene spans this region and produces a transmembrane protein that anchors in the membrane of the endoplasmic reticulum-Golgi intermediate compartment. Structural details regarding total exon count have not been extensively documented in current reference databases.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Variants in LMAN1 include missense changes, nonsense mutations, and deletions that can affect the protein's ability to bind cargo or localise correctly within the cell. Pathogenic variants typically result in loss of function, reducing the efficiency with which specific glycoproteins are transported through the secretory pathway. The inheritance pattern for conditions associated with LMAN1 variants varies depending on the specific genetic change and the cellular context in which the protein operates.
Sample of pathogenic variants
9 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.904A>T | p.Lys302Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Factor V and factor VIII, combined deficiency of, type 1 |
c.1356del | p.Asn452_Leu453insTer | Pathogenic | ★☆☆☆ | LMAN1-related disorder |
c.1366C>T | p.Arg456Ter | Pathogenic | ★☆☆☆ | Factor V and factor VIII, combined deficiency of, type 1 |
c.349C>T | p.Arg117Ter | Pathogenic | ★☆☆☆ | Factor V and factor VIII, combined deficiency of, type 1 |
c.539del | p.Asn180fs | Pathogenic | ★☆☆☆ | not provided |
c.604C>T | p.Arg202Ter | Pathogenic | ★☆☆☆ | Retinitis pigmentosa 7 |
c.1149+2T>C | - | Pathogenic | - | Factor V and factor VIII, combined deficiency of, type 1 |
c.2T>C | p.Met1Thr | Pathogenic | - | Factor V and factor VIII, combined deficiency of, type 1 |
c.796del | p.Gln266fs | Pathogenic | - | Factor V and factor VIII, combined deficiency of, type 1 |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
No specific inherited conditions have been formally recorded in association with LMAN1 in the current reference databases. However, research literature describes a link between LMAN1 variants and combined deficiency of coagulation factors, a rare bleeding disorder characterised by reduced levels of multiple clotting proteins despite normal synthesis of those factors. The clinical presentation and severity can vary depending on the specific genetic changes present.
No disease links recorded for this gene in our reference set.
UK clinical status
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What does the LMAN1 protein do in cells?
The LMAN1 protein acts as a cargo receptor, recognising and binding to specific glycoproteins in the endoplasmic reticulum and helping transport them to the Golgi apparatus. This ensures properly modified proteins advance through the secretory pathway.
How are LMAN1 variants inherited?
The inheritance pattern for LMAN1-associated conditions varies depending on the specific variant and clinical context. Some pathogenic changes may follow recessive inheritance, whilst other scenarios have been described in the research literature.
Is LMAN1 included in NHS genetic testing panels?
LMAN1 is not currently listed on NHS England Genomic Medicine Service PanelApp panels for routine clinical genomic testing. Testing availability may be guided by specific clinical presentations and consultant recommendations.