LMAN1

lectin, mannose binding 1

Basic information

Region (hg38): 18:59327823-59359265

Previous symbols: [ "F5F8D" ]

Links

ENSG00000074695 ∙ NCBI:3998 ∙ OMIM:601567 ∙ HGNC:6631 ∙ Uniprot:P49257 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• factor V and factor VIII, combined deficiency of, type 1 (Strong), mode of inheritance: AR
• factor V and factor VIII, combined deficiency of, type 1 (Strong), mode of inheritance: AR
• combined deficiency of factor V and factor VIII (Supportive), mode of inheritance: AR
• factor V and factor VIII, combined deficiency of, type 1 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Factor V and VIII, combined deficiency of, 1	AR	Hematologic	Individuals can suffer from bleeding diatheses of varying severity, and preventive measures related to bleeding episodes can be beneficial	Hematologic	13575936; 14452289; 4638375; 564138; 9045860; 9546392; 16304051; 18391077; 18685427; 19787799; 23006835

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LMAN1 gene.

• Factor V and factor VIII, combined deficiency of, type 1 (2 variants)
• LMAN1-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LMAN1 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	1	3	8
missense			45	4	3	52
nonsense	1	1				2
start loss						0
frameshift	1					1
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region			2	1	1	4
non coding			48	6	33	87
Total	2	2	97	11	39

Variants in LMAN1

This is a list of pathogenic ClinVar variants found in the LMAN1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
18-59327986-A-T		Factor V and factor VIII, combined deficiency of, type 1	Benign (Jan 13, 2018)
18-59328164-A-G		Factor V and factor VIII, combined deficiency of, type 1	Benign (Jan 12, 2018)
18-59328170-G-A		Factor V and factor VIII, combined deficiency of, type 1	Uncertain significance (Jan 12, 2018)
18-59328200-C-T		Factor V and factor VIII, combined deficiency of, type 1	Uncertain significance (Jan 12, 2018)
18-59328423-C-G		Factor V and factor VIII, combined deficiency of, type 1	Uncertain significance (Jan 13, 2018)
18-59328443-C-T		Factor V and factor VIII, combined deficiency of, type 1	Uncertain significance (Jan 12, 2018)
18-59328456-A-G		Factor V and factor VIII, combined deficiency of, type 1	Uncertain significance (Jan 13, 2018)
18-59328491-C-A		Factor V and factor VIII, combined deficiency of, type 1	Uncertain significance (Jan 12, 2018)
18-59328552-A-G		Factor V and factor VIII, combined deficiency of, type 1	Uncertain significance (Jan 13, 2018)
18-59328688-G-T		Factor V and factor VIII, combined deficiency of, type 1	Benign (Jan 12, 2018)
18-59328706-T-C		Factor V and factor VIII, combined deficiency of, type 1	Benign (Jan 12, 2018)
18-59328734-T-C		Factor V and factor VIII, combined deficiency of, type 1	Uncertain significance (Jan 13, 2018)
18-59328834-T-A		Factor V and factor VIII, combined deficiency of, type 1	Uncertain significance (Jan 13, 2018)
18-59328876-C-T		Factor V and factor VIII, combined deficiency of, type 1	Benign (Jan 13, 2018)
18-59328909-T-C		Factor V and factor VIII, combined deficiency of, type 1	Benign (Jan 13, 2018)
18-59328994-G-A		Factor V and factor VIII, combined deficiency of, type 1	Uncertain significance (Jan 13, 2018)
18-59329030-G-C		Factor V and factor VIII, combined deficiency of, type 1	Benign (Jan 13, 2018)
18-59329049-T-C		Factor V and factor VIII, combined deficiency of, type 1	Uncertain significance (Jan 13, 2018)
18-59329072-T-G		Factor V and factor VIII, combined deficiency of, type 1	Uncertain significance (Jan 13, 2018)
18-59329105-G-A		Factor V and factor VIII, combined deficiency of, type 1	Uncertain significance (Jan 13, 2018)
18-59329123-A-C		Factor V and factor VIII, combined deficiency of, type 1	Uncertain significance (Jan 13, 2018)
18-59329172-A-G		Factor V and factor VIII, combined deficiency of, type 1	Likely benign (Jan 13, 2018)
18-59329231-T-C		Factor V and factor VIII, combined deficiency of, type 1	Uncertain significance (Jan 12, 2018)
18-59329271-C-A		Factor V and factor VIII, combined deficiency of, type 1	Benign (Jan 13, 2018)
18-59329294-T-G		Factor V and factor VIII, combined deficiency of, type 1	Benign (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LMAN1	protein_coding	protein_coding	ENST00000251047	13	32140

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00426	0.996	125702	0	46	125748	0.000183

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0627	270	273	0.989	0.0000139	3357
Missense in Polyphen		78	90.325	0.86355		1152
Synonymous	-0.381	101	96.2	1.05	0.00000493	947
Loss of Function	3.50	10	31.1	0.322	0.00000178	345

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000563	0.000561
Ashkenazi Jewish	0.00	0.00
East Asian	0.000554	0.000544
Finnish	0.0000925	0.0000924
European (Non-Finnish)	0.000115	0.000114
Middle Eastern	0.000554	0.000544
South Asian	0.000163	0.000163
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Mannose-specific lectin. May recognize sugar residues of glycoproteins, glycolipids, or glycosylphosphatidyl inositol anchors and may be involved in the sorting or recycling of proteins, lipids, or both. The LMAN1-MCFD2 complex forms a specific cargo receptor for the ER-to-Golgi transport of selected proteins. {ECO:0000269|PubMed:12717434, ECO:0000269|PubMed:13130098}.
• Disease: DISEASE: Factor V and factor VIII combined deficiency 1 (F5F8D1) [MIM:227300]: A blood coagulation disorder characterized by bleeding symptoms similar to those in hemophilia or parahemophilia, that are caused by single deficiency of FV or FVIII, respectively. The most common symptoms are epistaxis, menorrhagia, and excessive bleeding during or after trauma. Plasma levels of coagulation factors V and VIII are in the range of 5 to 30% of normal. {ECO:0000269|PubMed:10090935, ECO:0000269|PubMed:19787799}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Protein processing in endoplasmic reticulum - Homo sapiens (human);Dengue-2 Interactions with Complement and Coagulation Cascades;Complement and Coagulation Cascades;Vesicle-mediated transport;Membrane Trafficking;Post-translational protein modification;Metabolism of proteins;Cargo concentration in the ER;Transport to the Golgi and subsequent modification;Asparagine N-linked glycosylation;Signaling events mediated by TCPTP;COPII-mediated vesicle transport;ER to Golgi Anterograde Transport (Consensus)

Recessive Scores

• pRec: 0.175

Intolerance Scores

• loftool: 0.443
• rvis_EVS: -0.05
• rvis_percentile_EVS: 50.34

Haploinsufficiency Scores

• pHI: 0.102
• hipred: Y
• hipred_score: 0.591
• ghis: 0.566

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.641

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Lman1
• Phenotype: hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); homeostasis/metabolism phenotype; cellular phenotype

Gene ontology

• Biological process: protein folding;endoplasmic reticulum to Golgi vesicle-mediated transport;endoplasmic reticulum organization;Golgi organization;blood coagulation;positive regulation of organelle organization;protein exit from endoplasmic reticulum;early endosome to Golgi transport;COPII vesicle coating;negative regulation of protein targeting to mitochondrion
• Cellular component: Golgi membrane;endoplasmic reticulum membrane;endoplasmic reticulum-Golgi intermediate compartment;cytosol;ER to Golgi transport vesicle membrane;membrane;integral component of membrane;sarcomere;COPII-coated ER to Golgi transport vesicle;endoplasmic reticulum-Golgi intermediate compartment membrane;host cell perinuclear region of cytoplasm;collagen-containing extracellular matrix;extracellular exosome
• Molecular function: protein binding;mannose binding;metal ion binding;unfolded protein binding