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

• adult-onset autosomal dominant demyelinating leukodystrophy (Limited), 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
• autosomal dominant primary microcephaly (Supportive), mode of inheritance: AD
• adult-onset autosomal dominant demyelinating leukodystrophy (Supportive), mode of inheritance: AD
• microcephaly 26, primary, autosomal dominant (Definitive), mode of inheritance: AD
• microcephaly (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; Leukodystrophy, demyelinating, adult-onset, autosomal dominant, atypical	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.

• not_provided (174 variants)
• Inborn_genetic_diseases (81 variants)
• Adult-onset_autosomal_dominant_demyelinating_leukodystrophy (29 variants)
• Microcephaly_26,_primary,_autosomal_dominant (15 variants)
• LMNB1-related_disorder (11 variants)
• not_specified (11 variants)
• Syndrome_with_microcephaly_as_major_feature (5 variants)
• LMNB1-related_primary_microcephaly (1 variants)
• Microcephaly (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. These statistics are base on transcript: NM_000005573.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	33	9	46
missense	4	1	145	22	2	174
nonsense			3			3
start loss			1			1
frameshift			5			5
splice donor/acceptor (+/-2bp)	1	1	5			7
Total	5	2	163	55	11

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
		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

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

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