LGMN

protein-coding

legumain

Gene summary

This gene encodes a cysteine protease that has a strict specificity for hydrolysis of asparaginyl bonds. This enzyme may be involved in the processing of bacterial peptides and endogenous proteins for MHC class II presentation in the lysosomal/endosomal systems. Enzyme activation is triggered by acidic pH and appears to be autocatalytic. Protein expression occurs after monocytes differentiate into dendritic cells. A fully mature, active enzyme is produced following lipopolysaccharide expression in mature dendritic cells. Overexpression of this gene may be associated with the majority of solid tumor types. This gene has a pseudogene on chromosome 13. Several alternatively spliced transcript variants have been described, but the biological validity of only two has been determined. These two variants encode the same isoform. [provided by RefSeq, Jul 2008]

Previous symbols:

PRSC1

MANE transcript

NM_005606.7

Inheritance

—

ClinVar variants

U:94B:3

Top phenotype

High myopia

gnomAD constraint

pLI —, LoF o/e 0.4

Max pathogenic AF

—

Genomic locus

chr14:92,703,807-92,748,679

External References & Databases

Ensembl (ENSG00000100600)

Transcript & Mutation Effects

hg38 • Region Span ~44.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LGMN variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 78

not providedTotal: 2

High myopiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005606.7. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar		1 clinvar	3
missense			85 clinvar	2 clinvar		87
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	0	94	2	1	97

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 104 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005606.7	RefSeq	NP_005597.3	13	MANE Select
ENST00000334869.9	Ensembl	ENSP00000334052.4	13	MANE Select
NM_001008530.3	RefSeq	NP_001008530.1	13	Standard
NM_001363696.2	RefSeq	NP_001350625.1	12	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
lgmn	Danio rerio	Structure: vertebra Quality: increased occurrence abnormal

Gene / Model

Organism

Observed Phenotype

lgmn

Danio rerio

Structure: vertebra

Quality: increased occurrence

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Antigen processing and presentation - Homo sapiens (human)
Lysosome - Homo sapiens (human)
Trafficking and processing of endosomal TLR
Toll-Like Receptors Cascades
MHC class II antigen presentation

Biological Process

renal system process
proteolysis
vacuolar protein processing
memory
positive regulation of cell population proliferation

Molecular Function

cysteine-type endopeptidase activity
peptidase activity
tau protein binding

Cellular Component

extracellular region
cytoplasm
lysosome
late endosome
endolysosome lumen

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000393218
Coding exons: 13
Length: 44896
Individuals with no LoFs: 125722
Homozygous LoFs: 0
Heterozygous LoFs: 26
Defined: 125748
p: 0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.22	204	259	0.787	0.0000146	2867
Missense (PolyPhen)		21	57.472	0.3654		668
Synonymous	0.537	100	107	0.934	0.00000745	797
Loss of Function	2.75	10	24.8	0.404	0.00000113	289

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000055	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00018	0.00018	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Has a strict specificity for hydrolysis of asparaginyl bonds. Can also cleave aspartyl bonds slowly, especially under acidic conditions. Required for normal lysosomal protein degradation in renal proximal tubules. Required for normal degradation of internalized EGFR. Plays a role in the regulation of cell proliferation via its role in EGFR degradation (By similarity). May be involved in the processing of proteins for MHC class II antigen presentation in the lysosomal/endosomal system. {ECO:0000250, ECO:0000269|PubMed:23776206}.;

Recessive Scores

pRec: 0.325

Intolerance Scores

LoFtool: 0.829
RVIS EVS: -0.02
RVIS percentile EVS: 52.09

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.521

Gene Damage Prediction

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