LMNB1

lamin B1, the group of Lamins

Basic information

Region (hg38): 5:126776623-126837020

Links

ENSG00000113368 ∙ NCBI:4001 ∙ OMIM:150340 ∙ HGNC:6637 ∙ Uniprot:P20700 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• microcephaly (Strong), mode of inheritance: AD
• adult-onset autosomal dominant demyelinating leukodystrophy (Limited), mode of inheritance: AD
• autosomal dominant primary microcephaly (Supportive), mode of inheritance: AD
• adult-onset autosomal dominant demyelinating leukodystrophy (Supportive), mode of inheritance: AD
• adult-onset autosomal dominant demyelinating leukodystrophy (Strong), mode of inheritance: AD
• microcephaly 26, primary, autosomal dominant (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Leukodystrophy, demyelinating, adult-onset, autosomal dominant; Microcephaly 26, primary, autosomal dominant	AD	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; Neurologic	16951681; 19151023; 21225301; 21909802; 23243074; 23649844; 32910914; 33033404

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LMNB1 gene.

• Microcephaly 26, primary, autosomal dominant (3 variants)
• Syndrome with microcephaly as major feature (3 variants)
• Inborn genetic diseases (2 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LMNB1 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	23	13	38
missense	2		88	8	4	102
nonsense			2			2
start loss			1			1
frameshift			3			3
inframe indel			3			3
splice donor/acceptor (+/-2bp)	1	1				2
splice region			4	8	1	13
non coding			19	14	22	55
Total	3	1	118	45	39

Variants in LMNB1

This is a list of pathogenic ClinVar variants found in the LMNB1 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-126776801-G-C		Leukodystrophy, Adult-Onset	Uncertain significance (Jun 14, 2016)
5-126776804-G-T		Leukodystrophy, Adult-Onset	Uncertain significance (Jun 14, 2016)
5-126776808-C-T		Leukodystrophy, Adult-Onset	Uncertain significance (Jun 14, 2016)
5-126776821-G-A		Leukodystrophy, Adult-Onset	Uncertain significance (Jun 14, 2016)
5-126776874-T-C		Leukodystrophy, Adult-Onset	Likely benign (Jun 14, 2016)
5-126776888-T-C		Leukodystrophy, Adult-Onset	Benign (Jun 14, 2016)
5-126776914-G-A		Leukodystrophy, Adult-Onset	Likely benign (Jun 14, 2016)
5-126776926-G-C		Leukodystrophy, Adult-Onset	Conflicting classifications of pathogenicity (Oct 01, 2022)
5-126776932-C-T		Leukodystrophy, Adult-Onset	Likely benign (Jun 14, 2016)
5-126776957-G-A		Leukodystrophy, Adult-Onset	Uncertain significance (Jun 14, 2016)
5-126776969-G-A		Leukodystrophy, Adult-Onset	Uncertain significance (Jun 14, 2016)
5-126777018-T-C		Leukodystrophy, Adult-Onset	Likely benign (Jun 14, 2016)
5-126777072-C-G		Leukodystrophy, Adult-Onset	Uncertain significance (Jun 14, 2016)
5-126777127-C-G		Leukodystrophy, Adult-Onset	Uncertain significance (Jun 14, 2016)
5-126777195-C-T		Adult-onset autosomal dominant demyelinating leukodystrophy	Benign (Jan 13, 2018)
5-126777211-G-T		Adult-onset autosomal dominant demyelinating leukodystrophy	Benign (Jan 12, 2018)
5-126777350-C-G		Adult-onset autosomal dominant demyelinating leukodystrophy	Uncertain significance (Jan 13, 2018)
5-126777433-G-T		Adult-onset autosomal dominant demyelinating leukodystrophy	Uncertain significance (Jan 13, 2018)
5-126777509-A-G			Uncertain significance (Jan 18, 2022)
5-126777521-A-G			Uncertain significance (May 21, 2021)
5-126777523-C-T			Likely benign (Oct 07, 2022)
5-126777524-C-T		Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 13, 2023)
5-126777526-C-T			Likely benign (Jan 13, 2023)
5-126777531-C-A		Inborn genetic diseases	Uncertain significance (Jan 23, 2024)
5-126777537-G-T		LMNB1-related disorder	Benign (Nov 22, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LMNB1	protein_coding	protein_coding	ENST00000261366	11	60398

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.555	0.445	125735	0	10	125745	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.63	229	310	0.740	0.0000166	3811
Missense in Polyphen		40	72.957	0.54826		1019
Synonymous	0.414	108	114	0.951	0.00000595	1114
Loss of Function	3.92	6	28.6	0.210	0.00000136	371

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000579	0.0000579
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000619	0.0000615
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
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: Leukodystrophy, demyelinating, autosomal dominant, adult- onset (ADLD) [MIM:169500]: A slowly progressive and fatal demyelinating leukodystrophy, presenting in the fourth or fifth decade of life. Clinically characterized by early autonomic abnormalities, pyramidal and cerebellar dysfunction, and symmetric demyelination of the CNS. It differs from multiple sclerosis and other demyelinating disorders in that neuropathology shows preservation of oligodendroglia in the presence of subtotal demyelination and lack of astrogliosis. {ECO:0000269|PubMed:16951681}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Apoptosis - Homo sapiens (human);Fas Ligand (FasL) pathway and Stress induction of Heat Shock Proteins (HSP) regulation;Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation;Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer,s disease models;Neurodegenerative Diseases;Disease;tnfr1 signaling pathway;caspase cascade in apoptosis;hiv-1 nef: negative effector of fas and tnf;Formation of Senescence-Associated Heterochromatin Foci (SAHF);DNA Damage/Telomere Stress Induced Senescence;Cellular Senescence;Cellular responses to stress;Breakdown of the nuclear lamina;Apoptotic cleavage of cellular proteins;Apoptotic execution phase;Apoptosis;Programmed Cell Death;Cellular responses to external stimuli;Depolymerisation of the Nuclear Lamina;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;Caspase Cascade in Apoptosis (Consensus)

Recessive Scores

• pRec: 0.521

Intolerance Scores

• loftool: 0.181
• rvis_EVS: -0.4
• rvis_percentile_EVS: 26.53

Haploinsufficiency Scores

• pHI: 0.932
• hipred: Y
• hipred_score: 0.739
• ghis: 0.611

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.889

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Lmnb1
• Phenotype: skeleton 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); 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); hematopoietic system phenotype; respiratory system phenotype; embryo phenotype; cellular phenotype; homeostasis/metabolism phenotype; craniofacial phenotype; muscle 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

Gene ontology

• Biological process: interleukin-12-mediated signaling pathway
• Cellular component: nucleus;nuclear envelope;nuclear inner membrane;lamin filament;nucleoplasm;membrane;nuclear matrix;nuclear membrane
• Molecular function: structural molecule activity;protein binding;phospholipase binding;sequence-specific double-stranded DNA binding