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…

Primary Disease Associations & Inheritance

?Intellectual developmental disorder, autosomal dominant 69MIM #617863

?Intellectual developmental disorder, autosomal recessive 52MIM #616887

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.29

LOEUF

—

Mechanism

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

Background carrier burden — how many people carry a rare variant somewhere in LMAN2L?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 240

463 rare PASS variants

Rare truncating (LoF)

1 in 1,500

73 rare PASS variants

Rare synonymous (reference)

1 in 280

196 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for LMAN2L. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 250	1 in 1,500
South Asian	~43k	1 in 250	1 in 2,400
Remaining (unassigned)	~30k	1 in 230	1 in 1,300
European (Finnish)	~27k	1 in 560	1 in 4,400
Admixed American	~22k	1 in 180	1 in 3,700
African / African American	~21k	1 in 170	1 in 1,600
East Asian	~20k	1 in 180	1 in 710
Ashkenazi Jewish	~13k	1 in 1,200	none seen
Middle Eastern	~2,884	1 in 170	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 8 coding exons well covered in gnomAD exomes and genomes.? see exons ↓