LMAN2L

Chr 2ADAR

lectin, mannose binding 2 like

Also known as: MRD69, MRT52, VIPL

NCBI Gene: 81562 ENSG00000114988 UniProt: Q9H0V9 OMIM: 609552

The protein functions as a non-cycling endoplasmic reticulum resident cargo receptor that regulates the export of glycoproteins from the ER to the Golgi apparatus and directs misfolded glycoproteins to the ubiquitin-proteasome pathway for degradation. Mutations cause intellectual developmental disorder with both autosomal dominant and autosomal recessive inheritance patterns reported. The gene shows relatively low constraint against loss-of-function variants (LOEUF 1.295), suggesting some tolerance to functional disruption.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein belonging to the L-type lectin group of type 1 membrane proteins, which function in the mammalian early secretory pathway. These proteins contain luminal carbohydrate recognition domains, which display homology to leguminous lectins. Unlike other proteins of the group, which cycle in the early secretory pathway and are predominantly associated with post endoplasmic reticulum membranes, the protein encoded by this gene is a non-cycling resident protein of the ER, where it functions as a cargo receptor for glycoproteins. It is proposed to regulate exchange of folded proteins for transport to the Golgi and exchange of misfolded glycoproteins for transport to the ubiquitin-proteasome pathway. [provided by RefSeq, Apr 2016]

OMIM ResearchGenerating clinical summary…

AD/ARLOEUF 1.292 OMIM phenotypes

Clinical Summary— LMAN2L

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

4 unique Pathogenic / Likely Pathogenic· 62 VUS of 87 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.29LOEUF

pLI 0.000

Z-score 0.53

OE 0.87 (0.60–1.29)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.19Z-score

OE missense 0.96 (0.86–1.08)

207 obs / 214.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.87 (0.60–1.29)

0≤0.351.4

Missense OE?0.96 (0.86–1.08)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 18 / 20.6Missense obs/exp: 207 / 214.8Syn Z: -0.24

ClinVar Variant Classifications

87 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

Likely Pathogenic1

VUS62

Likely Benign14

Benign1

Conflicting1

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	1	1	0	3
Likely Pathogenic	0	1	0	0	1
VUS	4	51	6	1	62
Likely Benign	0	1	2	11	14
Benign	0	0	1	0	1
Conflicting	—				1
Total	5	54	10	12	82

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

32 pathogenic / likely-pathogenic (of 65) ClinVar copy-number / structural variants overlap LMAN2L — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →