GeneBe

LEMD2

protein-coding

LEM domain nuclear envelope protein 2, the group of LEM domain containing

Gene summary

This gene encodes a LEM domain-containing transmembrane protein of the inner nuclear membrane. The protein is involved in nuclear structure organization and plays a role in cell signaling and differentiation. Mutations in this gene result in Cataract 46, juvenile-onset. Multiple transcript variants have been found for this gene. [provided by RefSeq, Feb 2017]

MANE transcript

NM_181336.4

Inheritance

AR, AD

ClinVar variants

P:2U:88B:36

Top phenotype

Marbach-Rustad progeroid syndrome; Cataract 46, juvenile onset, with or without arrhthythmic cardiomyopathy

gnomAD constraint

pLI —, LoF o/e 0.18

Max pathogenic AF

—

Genomic locus

chr6:33,771,202-33,789,130

External References & Databases

Ensembl (ENSG00000161904)NCBI Gene (221496)OMIM (616312)HGNC:21244GenCCUniProt (Q8NC56)AlphaFoldClinVar (LEMD2)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~17.9 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cataract 46 juvenile-onsetLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0008925

Submitter: Ambry Genetics

Marbach-Rustad progeroid syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0859147

Submitter: PanelApp Australia

cataract 46 juvenile-onsetSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0008925

Submitter: G2P

cataract 46 juvenile-onsetMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0008925

Submitter: PanelApp Australia

Marbach-Rustad progeroid syndromeMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0859147

Submitter: G2P

early-onset posterior subcapsular cataractSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0018610

Submitter: Orphanet

Marbach-Rustad progeroid syndromeLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0859147

Submitter: Ambry Genetics

total early-onset cataractSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0021548

Submitter: Orphanet

Marbach-Rustad progeroid syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0859147

Submitter: Labcorp Genetics (formerly Invitae)

cataract 46 juvenile-onsetLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0008925

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Marbach-Rustad progeroid syndrome; Cataract 46, juvenile onset, with or without arrhthythmic cardiomyopathyAD/AR

Manifestation: Cardiovascular; Dental; Endocrine; Neurologic; Ophthalmologic

Intervention: Cardiovascular; Endocrine

Rationale: Individuals with Marbach-Rustad progeroid syndrome have been described with cardiac manifestations, and awareness may allow early diagnosis and management; Individuals with Marbach-Rustad progeroid syndrome have been described as receiving treatment with growth hormone therapy; In Cataract 46, juvenile onset, with or without arrhthythmic cardiomyopathy, individuals have been described with cardiovascular manifestations including arrhythmic cardiomyopathy and sudden cardiac death, and awareness may allow early diagnosis and management; Heart transplant has been described

Refs: 23863954; 26788539; 30905398; 31061923Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LEMD2 variants in ClinVar

26 Conditions Cataloged
not specifiedTotal: 96
not providedTotal: 46
LEMD2-related disorderTotal: 10
Marbach-Rustad progeroid syndromeTotal: 3
Cataract 46 juvenile-onsetTotal: 2
LEMD2-related disordersTotal: 2
Thin skinTotal: 1
Developmental cataractTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_181336.4. 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.

EffectPLPVUSLBBSum
synonymous
28
clinvar
2
clinvar
 30
missense
1
clinvar
1
clinvar
81
clinvar
6
clinvar
 89
nonsense
1
clinvar
 1
start loss
1
clinvar
 1
frameshift
2
clinvar
 2
splice donor/acceptor (+/-2bp)
3
clinvar
 3
Total1188342126

Highest pathogenic variant AF is 0.0000034222244

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 39 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_181336.4RefSeqNP_851853.19MANE Select
ENST00000293760.10EnsemblENSP00000293760.59MANE Select
NM_001143944.1RefSeqNP_001137416.16Standard
NM_001348709.2RefSeqNP_001335638.16Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Clearance of Nuclear Envelope Membranes from Chromatin
  • Nuclear Envelope Breakdown
  • Mitotic Prophase
  • Initiation of Nuclear Envelope Reformation
  • Nuclear Envelope Reassembly

Biological Process

  • nuclear envelope organization
  • neurogenesis
  • negative regulation of BMP signaling pathway
  • skeletal muscle cell differentiation
  • negative regulation of MAPK cascade

Molecular Function

  • protein binding

Cellular Component

  • chromatin
  • nuclear envelope
  • nuclear inner membrane
  • integral component of nuclear inner membrane
  • endoplasmic reticulum

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000293760
Coding exons
9
Length
17935
Individuals with no LoFs
125735
Homozygous LoFs
0
Heterozygous LoFs
12
Defined
125747
p
0.0000477
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.821572350.6670.00001343121
Missense (PolyPhen)5588.6210.62062979
Synonymous0.8138898.30.8960.000005311077
Loss of Function3.58422.20.1800.00000121258

Population LoF Frequency

PopulationCAFp-valueStatus
African0.0000620.000062rare
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian0.0000540.000054rare
Finnish00.0absent
European (Non-Finnish)0.0000890.000088rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Involved in nuclear structure organization (PubMed:16339967). Required for maintaining the integrity of the nuclear envelope (PubMed:17097643). {ECO:0000269|PubMed:16339967, ECO:0000269|PubMed:17097643}.;

Recessive Scores

pRec
0.121

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
E
Essential (gene trap)
H
Indispensability pred.
E
Indispensability score
0.757

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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