LMNB2

lamin B2, the group of Lamins|MicroRNA protein coding host genes

Basic information

Region (hg38): 19:2427637-2456959

Previous symbols: [ "LMN2" ]

Links

ENSG00000176619 ∙ NCBI:84823 ∙ OMIM:150341 ∙ HGNC:6638 ∙ Uniprot:Q03252 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• microcephaly (Moderate), mode of inheritance: AD
• progressive myoclonic epilepsy type 9 (Limited), mode of inheritance: AR
• progressive myoclonic epilepsy type 9 (Supportive), mode of inheritance: AR
• lipodystrophy, partial, acquired, susceptibility to (Limited), mode of inheritance: AD
• progressive myoclonic epilepsy type 9 (Strong), mode of inheritance: AR
• microcephaly 27, primary, autosomal dominant (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Liopdystrophy, partial, acquired; Microcephaly 27, primary, autosomal dominant; Epilepsy, progressive myoclonic, 9	AD/AR	General	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	Craniofacial; Musculoskeletal; Neurologic	16826530; 22768673; 25954030; 33033404

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LMNB2 gene.

• Lipodystrophy, partial, acquired, susceptibility to;Progressive myoclonic epilepsy type 9 (240 variants)
• Progressive myoclonic epilepsy type 9;Lipodystrophy, partial, acquired, susceptibility to (216 variants)
• not provided (69 variants)
• Inborn genetic diseases (26 variants)
• not specified (11 variants)
• Progressive myoclonic epilepsy type 9 (7 variants)
• Acquired partial lipodystrophy (3 variants)
• LMNB2-related condition (3 variants)
• Neurodevelopmental disorder (2 variants)
• Microcephaly 27, primary, autosomal dominant (2 variants)
• Microcephaly 27, primary, autosomal dominant;Lipodystrophy, partial, acquired, susceptibility to;Progressive myoclonic epilepsy type 9 (1 variants)
• Generalized myoclonic seizure (1 variants)
• Microcephaly 27, primary, autosomal dominant;Lipodystrophy, partial, acquired, susceptibility to (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LMNB2 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			2	123	6	131
missense	1		200	32	16	249
nonsense			2			2
start loss						0
frameshift			2			2
inframe indel			3			3
splice donor/acceptor (+/-2bp)			2			2
splice region			7	27	4	38
non coding			2	34	37	73
Total	1	0	213	189	59

Variants in LMNB2

This is a list of pathogenic ClinVar variants found in the LMNB2 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-2430639-C-G			Benign (Jun 19, 2021)
19-2430889-TGTGTGGATGAGGA-T		LMNB2-related disorder	Likely benign (Jun 27, 2019)
19-2430909-G-T		LMNB2-related disorder	Likely benign (Jul 10, 2019)
19-2430915-A-G			Uncertain significance (Feb 01, 2023)
19-2430919-C-T		not specified	Uncertain significance (Mar 24, 2023)
19-2430920-G-A		Lipodystrophy, partial, acquired, susceptibility to;Progressive myoclonic epilepsy type 9	Likely benign (Aug 09, 2022)
19-2430922-A-G		Progressive myoclonic epilepsy type 9;Lipodystrophy, partial, acquired, susceptibility to • not specified	Conflicting classifications of pathogenicity (Mar 01, 2023)
19-2430927-C-A		Progressive myoclonic epilepsy type 9;Lipodystrophy, partial, acquired, susceptibility to	Uncertain significance (Jun 01, 2022)
19-2430932-T-C		Progressive myoclonic epilepsy type 9;Lipodystrophy, partial, acquired, susceptibility to	Likely benign (Jan 15, 2024)
19-2430939-G-A		Lipodystrophy, partial, acquired, susceptibility to;Progressive myoclonic epilepsy type 9	Uncertain significance (Nov 27, 2023)
19-2430944-C-A		Progressive myoclonic epilepsy type 9;Lipodystrophy, partial, acquired, susceptibility to	Likely benign (Dec 01, 2020)
19-2430944-C-T		Lipodystrophy, partial, acquired, susceptibility to;Progressive myoclonic epilepsy type 9	Likely benign (Nov 18, 2023)
19-2430952-C-T		Lipodystrophy, partial, acquired, susceptibility to;Progressive myoclonic epilepsy type 9	Uncertain significance (May 01, 2021)
19-2430956-CAGGA-C		Progressive myoclonic epilepsy type 9;Lipodystrophy, partial, acquired, susceptibility to	Likely benign (Aug 16, 2022)
19-2430956-C-CAGGA		Lipodystrophy, partial, acquired, susceptibility to;Progressive myoclonic epilepsy type 9	Likely benign (Nov 01, 2022)
19-2430956-C-CAGGAAGGA		Progressive myoclonic epilepsy type 9;Lipodystrophy, partial, acquired, susceptibility to	Likely benign (May 24, 2023)
19-2430962-G-C		Lipodystrophy, partial, acquired, susceptibility to;Progressive myoclonic epilepsy type 9	Likely benign (Jan 11, 2024)
19-2430969-A-G		Progressive myoclonic epilepsy type 9;Lipodystrophy, partial, acquired, susceptibility to	Benign (Dec 19, 2023)
19-2431172-G-A			Benign (Jun 19, 2021)
19-2431257-G-A			Benign (Jun 19, 2021)
19-2431274-T-G			Benign (Jun 19, 2021)
19-2431532-G-A		Progressive myoclonic epilepsy type 9;Lipodystrophy, partial, acquired, susceptibility to	Likely benign (Jan 25, 2023)
19-2431533-G-A		Progressive myoclonic epilepsy type 9;Lipodystrophy, partial, acquired, susceptibility to	Likely benign (Jun 16, 2022)
19-2431533-G-C		Progressive myoclonic epilepsy type 9;Lipodystrophy, partial, acquired, susceptibility to	Likely benign (Jan 10, 2023)
19-2431535-A-G		Lipodystrophy, partial, acquired, susceptibility to;Progressive myoclonic epilepsy type 9	Likely benign (Mar 19, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LMNB2	protein_coding	protein_coding	ENST00000325327	12	29359

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000414	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.659	359	396	0.907	0.0000299	3991
Missense in Polyphen		113	153.71	0.73516		1492
Synonymous	-0.474	187	179	1.05	0.0000144	1252
Loss of Function	4.95	0	28.5	0.00	0.00000142	330

LoF frequencies by population

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

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Lamins are components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane, which is thought to provide a framework for the nuclear envelope and may also interact with chromatin.
• Disease: DISEASE: Partial acquired lipodystrophy (APLD) [MIM:608709]: A rare childhood disease characterized by loss of subcutaneous fat from the face and trunk. Fat deposition on the pelvic girdle and lower limbs is normal or excessive. Most frequently, onset between 5 and 15 years of age. Most affected subjects are females and some show no other abnormality, but many develop glomerulonephritis, diabetes mellitus, hyperlipidemia, and complement deficiency. Mental retardation in some cases. APLD is a sporadic disorder of unknown etiology. {ECO:0000269|PubMed:16826530, ECO:0000269|PubMed:22768673}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Epilepsy, progressive myoclonic 9 (EPM9) [MIM:616540]: An autosomal recessive form of progressive myoclonic epilepsy, a rare disease initially responsive to antiepileptic drugs which over time becomes refractory and can be associated with cognitive decline. EPM9 features include myoclonus, tonic-clonic seizures, ataxia, and psychomotor development. {ECO:0000269|PubMed:25954030}. Note=The disease may be caused by mutations affecting the gene represented in this entry.
• Pathway: Apoptosis - Homo sapiens (human);miR-targeted genes in epithelium - TarBase;miR-targeted genes in leukocytes - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Gastric Cancer Network 2;Fas Ligand (FasL) pathway and Stress induction of Heat Shock Proteins (HSP) regulation;tnfr1 signaling pathway;caspase cascade in apoptosis;hiv-1 nef: negative effector of fas and tnf;Caspase Cascade in Apoptosis (Consensus)

Recessive Scores

• pRec: 0.243

Intolerance Scores

• rvis_EVS: -1.13
• rvis_percentile_EVS: 6.51

Haploinsufficiency Scores

• pHI: 0.838
• hipred: Y
• hipred_score: 0.696
• ghis: 0.701

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.804

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Lmnb2
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism 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); respiratory system phenotype; embryo phenotype

Gene ontology

• Biological process: biological_process
• Cellular component: nuclear inner membrane;lamin filament;nuclear membrane
• Molecular function: molecular_function;structural molecule activity;protein binding