LMAN2L

protein-coding

lectin, mannose binding 2 like

Gene summary

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]

MANE transcript

NM_030805.4

Inheritance

AR, AD

ClinVar variants

P:4U:60B:14

Top phenotype

Intellectual developmental disorder, autosomal dominant 69; Intellectual developmental disorder, autosomal recessive, 52

gnomAD constraint

pLI —, LoF o/e 0.87

Max pathogenic AF

—

Genomic locus

chr2:96,705,929-96,740,064

External References & Databases

Ensembl (ENSG00000114988)

Transcript & Mutation Effects

hg38 • Region Span ~34.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

intellectual disability, autosomal recessive 52LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0014815

Submitter: Ambry Genetics

intellectual disability, autosomal recessive 52MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014815

Submitter: PanelApp Australia

intellectual disability, autosomal recessive 52LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0014815

Submitter: Labcorp Genetics (formerly Invitae)

intellectual disability, autosomal recessive 52LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0014815

Submitter: Ambry Genetics

complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

autosomal recessive non-syndromic intellectual disabilitySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0019502

Submitter: Orphanet

intellectual developmental disorder, autosomal dominant 69MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0029465

Submitter: PanelApp Australia

intellectual developmental disorder, autosomal dominant 69LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0029465

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Intellectual developmental disorder, autosomal dominant 69; Intellectual developmental disorder, autosomal recessive, 52AD/AR

Manifestation: Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 26566883; 31020005

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LMAN2L variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 53

not providedTotal: 20

Intellectual disability, autosomal recessive 52Total: 12

LMAN2L-related disorderTotal: 6

Intellectual developmental disorder, autosomal dominant 69Total: 2

Neurodevelopmental disorderTotal: 1

Hyperphosphatasia with intellectual disability syndrome 4Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_030805.4. 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	13 clinvar		15
missense	1 clinvar	1 clinvar	54 clinvar	1 clinvar		57
nonsense						0
start loss						0
frameshift	1 clinvar	1 clinvar	2 clinvar			4
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	2	2	60	14	0	78

Highest pathogenic variant AF is 0.000030360408

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 42 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_030805.4	RefSeq	NP_110432.1	8	MANE Select
ENST00000264963.9	Ensembl	ENSP00000264963.4	8	MANE Select
NM_001142292.2	RefSeq	NP_001135764.1	9	Standard
NM_001322346.2	RefSeq	NP_001309275.1	6	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
lman2la	Danio rerio	Structure: neuromast hair cell Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

lman2la

Danio rerio

Structure: neuromast hair cell

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Vesicle-mediated transport
Membrane Trafficking
Post-translational protein modification
Metabolism of proteins
Cargo concentration in the ER

Biological Process

protein folding
endoplasmic reticulum to Golgi vesicle-mediated transport
endoplasmic reticulum organization
Golgi organization
protein transport

Molecular Function

mannose binding
metal ion binding

Cellular Component

Golgi membrane
endoplasmic reticulum membrane
endoplasmic reticulum-Golgi intermediate compartment
Golgi apparatus
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000377079
Coding exons: 9
Length: 34136
Individuals with no LoFs: 125679
Homozygous LoFs: 0
Heterozygous LoFs: 69
Defined: 125748
p: 0.000274

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.188	207	215	0.964	0.0000120	2329
Missense (PolyPhen)		79	88.665	0.89099		932
Synonymous	-0.235	86	83.3	1.03	0.00000433	706
Loss of Function	0.533	18	20.6	0.873	0.00000102	220

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00044	0.00044	rare
South Asian	0.00016	0.00016	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be involved in the regulation of export from the endoplasmic reticulum of a subset of glycoproteins. May function as a regulator of ERGIC-53. {ECO:0000269|PubMed:12878160}.;

Recessive Scores

pRec: 0.127

Intolerance Scores

LoFtool: 0.820
RVIS EVS: -0.65
RVIS percentile EVS: 16.36

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.157

Gene Damage Prediction

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