LEMD2

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

Basic information

Region (hg38): 6:33771201-33789130

Links

ENSG00000161904 ∙ NCBI:221496 ∙ OMIM:616312 ∙ HGNC:21244 ∙ Uniprot:Q8NC56 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cataract 46 juvenile-onset (Limited), mode of inheritance: AR
• total early-onset cataract (Supportive), mode of inheritance: AD
• early-onset posterior subcapsular cataract (Supportive), mode of inheritance: AD
• cataract 46 juvenile-onset (Strong), mode of inheritance: AR
• cataract 46 juvenile-onset (Limited), mode of inheritance: AR
• Marbach-Rustad progeroid syndrome (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Marbach-Rustad progeroid syndrome; Cataract 46, juvenile onset, with or without arrhthythmic cardiomyopathy	AD/AR	Cardiovascular; Endocrine	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	Cardiovascular; Dental; Endocrine; Neurologic; Ophthalmologic	23863954; 26788539; 30905398; 31061923

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LEMD2 gene.

• Cataract 46 juvenile-onset (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LEMD2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				6	3	9
missense	1	1	29	2	3	36
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				2	1	3
non coding				1	16	17
Total	1	1	29	9	22

Variants in LEMD2

This is a list of pathogenic ClinVar variants found in the LEMD2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-33772548-G-C			Benign (May 12, 2021)
6-33772605-G-A			Benign (May 12, 2021)
6-33772638-G-A		not specified	Uncertain significance (Feb 16, 2023)
6-33772704-G-A		19 conditions • Marbach-Rustad progeroid syndrome	Likely pathogenic (Mar 21, 2019)
6-33772710-G-A		not specified • Cataract 46 juvenile-onset	Uncertain significance (Jan 26, 2022)
6-33772774-G-A		not specified	Uncertain significance (Nov 22, 2022)
6-33772790-G-A			Likely benign (Jul 19, 2022)
6-33772815-C-T			Benign (May 12, 2021)
6-33772927-AGAG-A			Benign (May 13, 2021)
6-33776934-C-T			Benign (Jan 27, 2024)
6-33776945-G-A			Benign (Jan 15, 2024)
6-33777037-G-A			Benign/Likely benign (Dec 01, 2023)
6-33777103-G-A			Benign (May 13, 2021)
6-33777105-C-G			Benign (May 12, 2021)
6-33777134-G-A		LEMD2-related disorder	Likely benign (Dec 07, 2023)
6-33777182-T-C			Uncertain significance (Nov 18, 2023)
6-33777197-C-T		not specified	Uncertain significance (Aug 17, 2021)
6-33777205-T-C			Likely benign (Dec 17, 2022)
6-33777294-C-T			Benign (May 12, 2021)
6-33778314-G-A			Uncertain significance (Sep 27, 2022)
6-33778319-T-C			Uncertain significance (Jun 09, 2022)
6-33778343-T-C		not specified	Uncertain significance (Mar 20, 2024)
6-33778366-A-T		LEMD2-related disorder	Likely benign (Oct 28, 2019)
6-33780110-C-T		not specified	Uncertain significance (Dec 20, 2023)
6-33780115-T-C		LEMD2-related disorder	Benign/Likely benign (Jul 03, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LEMD2	protein_coding	protein_coding	ENST00000293760	9	17935

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.753	0.247	125735	0	12	125747	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.82	157	235	0.667	0.0000134	3121
Missense in Polyphen		55	88.621	0.62062		979
Synonymous	0.813	88	98.3	0.896	0.00000531	1077
Loss of Function	3.58	4	22.2	0.180	0.00000121	258

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000617	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000890	0.0000879
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

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}.
• Pathway: Clearance of Nuclear Envelope Membranes from Chromatin;Nuclear Envelope Breakdown;Mitotic Prophase;Initiation of Nuclear Envelope Reformation;Nuclear Envelope Reassembly;Mitotic Anaphase;Mitotic Metaphase and Anaphase;M Phase;Cell Cycle;Cell Cycle, Mitotic (Consensus)

Recessive Scores

• pRec: 0.121

Haploinsufficiency Scores

• pHI: 0.223
• hipred: Y
• hipred_score: 0.520
• ghis: 0.499

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.757

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Lemd2
• Phenotype: growth/size/body region phenotype; cellular phenotype; craniofacial phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); muscle phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; embryo phenotype; vision/eye phenotype

Gene ontology

• Biological process: nuclear envelope organization;neurogenesis;negative regulation of BMP signaling pathway;skeletal muscle cell differentiation;negative regulation of MAPK cascade;negative regulation of protein kinase B signaling;heart formation;protein localization to chromatin
• Cellular component: chromatin;nuclear envelope;nuclear inner membrane;integral component of nuclear inner membrane;endoplasmic reticulum;membrane;integral component of membrane;nuclear membrane
• Molecular function: protein binding