LMNB1

Summary

LMNB1 (lamin B1, HGNC:6637) is a protein-coding gene on chromosome 5q23.2, encoding Lamin-B1 (P20700). Lamins are intermediate filament proteins that assemble into a filamentous meshwork, and which constitute the major components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane.

This gene encodes one of the two B-type lamin proteins and is a component of the nuclear lamina. A duplication of this gene is associated with autosomal dominant adult-onset leukodystrophy (ADLD). Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 4001 — RefSeq curated summary.

At a glance

• Gene–disease (curated): microcephaly 26, primary, autosomal dominant (Definitive, ClinGen) — +5 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 334 total — 12 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 106
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity sufficient evidence
• MANE Select transcript: NM_005573

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6637
Approved symbol	LMNB1
Name	lamin B1
Location	5q23.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000113368
Ensembl biotype	protein_coding
OMIM	150340
Entrez	4001

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 protein_coding, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000261366, ENST00000395354, ENST00000460265, ENST00000463908, ENST00000472034, ENST00000492190, ENST00000494185, ENST00000504788, ENST00000899476, ENST00000919398, ENST00000919399

RefSeq mRNA: 2 — MANE Select: NM_005573 NM_001198557, NM_005573

CCDS: CCDS4140

Canonical transcript exons

ENST00000261366 — 11 exons

Exon	Start	End
ENSE00001294154	126777136	126777867
ENSE00001851578	126836223	126837020
ENSE00003504370	126818922	126819142
ENSE00003587703	126811773	126811898
ENSE00003624568	126820910	126821135
ENSE00003625173	126832694	126832801
ENSE00003626964	126810180	126810350
ENSE00003658398	126804776	126804932
ENSE00003658821	126822781	126822885
ENSE00003661838	126805571	126805696
ENSE00003670060	126825988	126826107

Expression profiles

Bgee: expression breadth ubiquitous, 226 present calls, max score 99.32.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 73.9451 / max 1118.4526, expressed in 1776 samples.

FANTOM5 promoters (16 alternative TSS)

Promoter ID	TPM avg	Samples expressed
58298	64.8198	1765
58311	2.0735	194
58312	1.8753	219
58297	1.2301	647
58300	1.1743	405
58301	0.7753	195
58303	0.3555	143
58305	0.3357	137
58306	0.3274	170
58302	0.2199	67

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	99.32	gold quality
ganglionic eminence	UBERON:0004023	99.03	gold quality
embryo	UBERON:0000922	97.09	gold quality
monocyte	CL:0000576	95.97	gold quality
cortical plate	UBERON:0005343	95.63	gold quality
mononuclear cell	CL:0000842	95.34	gold quality
leukocyte	CL:0000738	95.13	gold quality
rectum	UBERON:0001052	93.18	gold quality
vermiform appendix	UBERON:0001154	93.01	gold quality
mucosa of transverse colon	UBERON:0004991	92.46	gold quality
bone marrow	UBERON:0002371	92.24	gold quality
blood	UBERON:0000178	91.74	gold quality
bone marrow cell	CL:0002092	91.73	gold quality
buccal mucosa cell	CL:0002336	91.17	silver quality
caecum	UBERON:0001153	88.89	gold quality
granulocyte	CL:0000094	88.75	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.31	gold quality
colonic epithelium	UBERON:0000397	87.23	gold quality
lymph node	UBERON:0000029	87.05	gold quality
mucosa of sigmoid colon	UBERON:0004993	86.86	gold quality
thymus	UBERON:0002370	86.29	gold quality
secondary oocyte	CL:0000655	86.11	gold quality
stromal cell of endometrium	CL:0002255	85.32	gold quality
colonic mucosa	UBERON:0000317	84.88	gold quality
esophagus mucosa	UBERON:0002469	84.68	gold quality
spleen	UBERON:0002106	84.42	gold quality
tonsil	UBERON:0002372	84.02	gold quality
adrenal tissue	UBERON:0018303	83.89	gold quality
oocyte	CL:0000023	83.52	gold quality
endometrium epithelium	UBERON:0004811	82.75	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-GEOD-124472	yes	176.79
E-CURD-122	yes	23.99
E-GEOD-125970	yes	22.68
E-HCAD-5	yes	17.55
E-MTAB-8498	yes	8.86
E-MTAB-10553	yes	7.01
E-ANND-3	yes	4.34
E-MTAB-6911	no	121.26
E-CURD-88	no	3.68

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

45 targeting LMNB1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-2053	99.57	69.15	1635
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-4753-5P	99.54	68.51	1356
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-569	99.42	66.32	1009
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-1276	99.36	68.18	1642
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-1253	99.12	67.08	1688

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 3 (sufficient evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• colocalizes with lamin B1 in the nucleoplasm and around the nuclear rim during S-phase of cells transfected with EBNA-1 in the absence of EBV plasmids. (PMID:12898336)
• organization of the nuclear envelope and lamina is dependent on a mechanism involving the methylation of lamin B1 (PMID:14504265)
• the distinctive ensemble of heterotypic lamin interactions in a particular cell type affects the stability of the lamin polymer (PMID:15284226)
• We now show that epitope masking in the nucleus is often responsible for failure to detect emerin and lamins in human, rat and pig tissues.These data suggest that different regions of the lamin B1 molecule are masked in different tissues. (PMID:16283426)
• Apoptotic neutrophils express lamin B1 on their surface; these cells may participate in the development of autoantibodies directed against cytoskeletal proteins, a condition frequently reported in several inflammatory diseases. (PMID:16365157)
• Results suggest that the C-terminus of nuclear titin binds lamins A and B in vivo and might contribute to nuclear organization during interphase. (PMID:16410549)
• lamin B was essential for the formation of the mitotic matrix that tethers a number of spindle assembly factors; propose that lamin B is a structural component of the spindle matrix that promotes microtubule assembly and organization in mitosis (PMID:16543417)
• Results show that a lamin B1-containing nucleoskeleton is required to maintain RNA synthesis and that ongoing synthesis is a fundamental determinant of global nuclear architecture in mammalian cells. (PMID:18334554)
• lamin A/C, lamin B1, and viral US3 kinase have roles in viral infectivity, virion egress, and the targeting of herpes simplex virus U(L)34-encoded protein to the inner nuclear membrane (PMID:18524819)
• Novel duplication on chromosomal band 5q23.2 in a French Canadian family with autosomal dominant leukodystrophy that supports the implication of duplicated LMNB1 as the disease-causing mutation. (PMID:19001169)
• Silencing lamin B1 expression dramatically increases the lamina meshwork size and the mobility of nucleoplasmic lamin A (PMID:19141474)
• duplication of the lamin B1 gene (LMNB1) has recently been described in a rare form of autosomal dominant adult-onset leukoencephalopathy. (PMID:19151023)
• Nudel regulates microtubule organization in part by facilitating assembly of the lamin B spindle matrix in a dynein-dependent manner. (PMID:19198602)
• Our work indicates that lamin B1 defects are probably not responsible for signs and symptoms resembling multiple sclerosis. (PMID:19348623)
• Lamin B1 maintains the functional plasticity of nucleoli. (PMID:19383719)
• Proteomics identified lamin B1 as being significantly upregulated in HCC tumors and present in patients’ plasma. (PMID:19522540)
• results suggest that a LMNB1 regulatory sequence mutation underlies the variant adult-onset autosomal dominant leukodystrophy (ADLD) phenotype; adult forms of ADLD linked to 5q23 may be more heterogeneous clinically and genetically than previously thought (PMID:19961535)
• These findings indicate that a lamin dimer principally has the freedom for a “combinatorial” head-to-tail association with all types of lamins, a property that might be of significant importance for the assembly of the nuclear lamina. (PMID:20004208)
• Autosomal dominant leukodystrophy is the first disease that has ever been linked to lamin B1 mutations and it expands the pathological role of the nuclear lamia to include disorders of the brain. (PMID:20816241)
• SNP array analysis revealed novel duplications spanning the entire LMNB1 gene in probands from each of four adult-onset autosomal dominant leukodystrophy families (PMID:21225301)
• This study demonistrated that Adult-onset autosomal dominant leukodystrophy due to LMNB1 gene duplication. (PMID:21909802)
• LB1 expression in WI-38 cells decreases during cellular senescence (PMID:22155925)
• The authors show that oxidative stress increases lamin B1 levels through p38 Mitogen Activated Protein kinase activation. (PMID:22246186)
• crystal structures of lamin B1 globular tail domain and coiled 2B domain, with similar folds to Ig-like domain and coiled-coil domain of lamin A. Found an extra intermolecular disulfide bond in lamin B1 coil 2B domain, which does not exist in lamin A/C. (PMID:22265972)
• Lamin B1 is lost from primary human and murine cell strains when they are induced to senesce. (PMID:22496421)
• Results indicate that lamin B1 (LMNB1) accumulation in adult-onset autosomal dominant leukodystrophy (ADLD) is associated with Oct-1 recruitment. (PMID:23261988)
• LMNB1 protein levels decline in senescent human dermal fibroblasts and keratinocytes, mediated by reduced transcription and inhibition of LMNB1 messenger ribonucleic acid translation by miRNA-23a. (PMID:23439683)
• Treating normal human fibroblasts with farnesyltransferase inhibitors causes the accumulation of unprocessed lamin B2 and lamin A and a decrease in mature lamin B1. (PMID:23475125)
• detailed molecular analysis of the largest collection of autosomal dominant leukodystrophy (ADLD) families studied, to date; identified the minimal duplicated region necessary for the disease, defined all the duplication junctions at the nucleotide level and identified the first inverted LMNB1 duplication (PMID:23649844)
• we confirm the underlying role of lamin B1 duplication, regardless of the autonomic malfunction onset in Adult-onset autosomal dominant leukodystrophy (PMID:23681646)
• Rare variants of LMNB1 may contribute to susceptibility to neural tube defects. (PMID:23733478)
• Lamin B1 plays an important role in pancreatic cancer pathogenesis and is a novel therapeutic target of betulinic acid treatment. (PMID:23857605)
• The regulation of lamin B1 is important for cellular physiology and disease.To how perturbations of lamin B1 affect cellular physiology and discuss the implications this has on senescence, HGPS and ADLD. (PMID:23873483)
• lamin B1 down-regulation in senescence is a key trigger of global and local chromatin changes that impact gene expression, aging, and cancer (PMID:23934658)
• LMNB1 may contribute to senescence in at least two ways due to its uneven genome-wide redistribution: first, through the spatial reorganization of chromatin and, second, through gene repression. (PMID:23964094)
• Higher levels of A-type lamins and lamin B1 mRNA expression were seen in associated non-cancerous tissue. Higher lamin A/C expression was associated with the early clinical breast cancer stage, with better clinical outcomes. (PMID:24293108)
• This led us to propose a model where the nucleolus has steady-state stiffness dependent on ribosome biogenesis activity and requires LaminB1 for its flexibility. (PMID:24297448)
• LMNB1 is required to maintain chromatin condensation in interphase nuclei. (PMID:24732130)
• Lamin B1 overexpression increases nuclear rigidity in autosomal dominant leukodystrophy fibroblasts. (PMID:24858279)
• Nuclear envelope remodelling during human spermiogenesis involves somatic B-type lamins and a spermatid-specific B3 lamin isoform. (PMID:25477337)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lmnb1	ENSDARG00000044299
mus_musculus	Lmnb1	ENSMUSG00000024590
rattus_norvegicus	Lmnb1	ENSRNOG00000013774

Paralogs (68): KRT33A (ENSG00000006059), VIM (ENSG00000026025), KRT31 (ENSG00000094796), NEFM (ENSG00000104722), KRT23 (ENSG00000108244), KRT37 (ENSG00000108417), KRT32 (ENSG00000108759), KRT18 (ENSG00000111057), KRT36 (ENSG00000126337), KRT17 (ENSG00000128422), GFAP (ENSG00000131095), KRT34 (ENSG00000131737), KRT33B (ENSG00000131738), NES (ENSG00000132688), PRPH (ENSG00000135406), KRT85 (ENSG00000135443), KRT7 (ENSG00000135480), KRT71 (ENSG00000139648), INA (ENSG00000148798), LMNTD1 (ENSG00000152936), LMNA (ENSG00000160789), KRT84 (ENSG00000161849), KRT82 (ENSG00000161850), KRT80 (ENSG00000167767), KRT1 (ENSG00000167768), KRT24 (ENSG00000167916), KRT8 (ENSG00000170421), KRT78 (ENSG00000170423), KRT86 (ENSG00000170442), KRT75 (ENSG00000170454), KRT6C (ENSG00000170465), KRT4 (ENSG00000170477), KRT74 (ENSG00000170484), KRT72 (ENSG00000170486), KRT83 (ENSG00000170523), BFSP2 (ENSG00000170819), KRT19 (ENSG00000171345), KRT15 (ENSG00000171346), KRT38 (ENSG00000171360), KRT13 (ENSG00000171401)

Protein

Protein identifiers

Lamin-B1 — P20700 (reviewed: P20700)

All UniProt accessions (4): P20700, A0A0D9SFE5, A0A0D9SFY5, E9PBF6

UniProt curated annotations — full annotation on UniProt →

Function. Lamins are intermediate filament proteins that assemble into a filamentous meshwork, and which constitute the major components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane. Lamins provide a framework for the nuclear envelope, bridging the nuclear envelope and chromatin, thereby playing an important role in nuclear assembly, chromatin organization, nuclear membrane and telomere dynamics. The structural integrity of the lamina is strictly controlled by the cell cycle, as seen by the disintegration and formation of the nuclear envelope in prophase and telophase, respectively.

Subunit / interactions. Homodimer. Lamin dimers then assemble into dimeric head-to-tail polymers. Ultimately, two head-to-tail polymers assemble laterally into a protofilament with a uniformly shaped rod of 3.5 nm in diameter. Interacts with SPAG4 and SEPT12.

Subcellular location. Nucleus lamina.

Post-translational modifications. B-type lamins undergo a series of modifications, such as farnesylation and phosphorylation. Increased phosphorylation of the lamins occurs before envelope disintegration and probably plays a role in regulating lamin associations. Phosphorylation plays a key role in lamin organization, subcellular localization and nuclear envelope disintegration. Phosphorylation by CDK1 at Ser-23 and Ser-393 at the onset of mitosis drives lamin disassembly and nuclear envelope breakdown.

Disease relevance. Leukodystrophy, demyelinating, adult-onset, autosomal dominant, typical (ADLDTY) [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. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by heterozygous tandem genomic duplications that result in an extra copy of the LMNB1 gene and also affect regulatory elements of other genes. Leukodystrophy, demyelinating, adult-onset, autosomal dominant, atypical (ADLDAT) [MIM:621061] An autosomal dominant, slowly progressive disorder characterized by pyramidal signs with muscle weakness, spasticity, dysarthria, dysautonomia, and demyelinating leukodystrophy affecting the cerebrum and cortico-spinal tracts while sparing the cerebellum. Patients usually do not present with autonomic symptoms. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by abnormal LMNB1 expression due to heterozygous deletions involving regulatory elements upstream of LMNB1. It can also be caused by inverted duplications involving LMNB1, as reported in one patient. Microcephaly 26, primary, autosomal dominant (MCPH26) [MIM:619179] A form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age, sex and ethnically matched mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. MCPH26 is an autosomal dominant, progressive form apparent at birth or in early infancy. It is associated with relative short stature, variable severity of intellectual disability, and neurological features as the core symptoms. Brain imaging shows a simplified gyral pattern of the cortex and abnormal corpus callosum in some patients. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the intermediate filament family.

RefSeq proteins (2): NP_001185486, NP_005564* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001322	Lamin_tail_dom	Domain
IPR018039	IF_conserved	Conserved_site
IPR036415	Lamin_tail_dom_sf	Homologous_superfamily
IPR039008	IF_rod_dom	Domain

Pfam: PF00038, PF00932

UniProt features (79 total): modified residue 26, cross-link 12, strand 10, region of interest 9, sequence variant 9, domain 2, initiator methionine 1, chain 1, short sequence motif 1, compositionally biased region 1, propeptide 1, lipid moiety-binding region 1, glycosylation site 1, disulfide bond 1, sequence conflict 1, helix 1, turn 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
3UMN	X-RAY DIFFRACTION	2
3JT0	X-RAY DIFFRACTION	2.39
3TYY	X-RAY DIFFRACTION	2.4
5BNW	X-RAY DIFFRACTION	2.4
5VVX	X-RAY DIFFRACTION	2.9
7DTG	X-RAY DIFFRACTION	3.6
2KPW	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P20700-F1	82.95	0.67

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (39): 2, 3, 5, 14, 20, 23, 25, 28, 111, 126, 157, 158, 200, 210, 232, 271, 278, 302, 330, 375 …

Disulfide bonds (1): 317

Glycosylation sites (1): 399

Function

Pathways and Gene Ontology

Reactome pathways

40 pathways

ID	Pathway
R-HSA-1221632	Meiotic synapsis
R-HSA-2559584	Formation of Senescence-Associated Heterochromatin Foci (SAHF)
R-HSA-2980766	Nuclear Envelope Breakdown
R-HSA-2995383	Initiation of Nuclear Envelope (NE) Reformation
R-HSA-352238	Breakdown of the nuclear lamina
R-HSA-4419969	Depolymerization of the Nuclear Lamina
R-HSA-8862803	Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer’s disease models
R-HSA-8950505	Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation
R-HSA-9013405	RHOD GTPase cycle
R-HSA-9035034	RHOF GTPase cycle
R-HSA-109581	Apoptosis
R-HSA-111465	Apoptotic cleavage of cellular proteins
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-1474165	Reproduction
R-HSA-1500620	Meiosis
R-HSA-162582	Signal Transduction
R-HSA-1640170	Cell Cycle
R-HSA-1643685	Disease
R-HSA-168256	Immune System
R-HSA-194315	Signaling by Rho GTPases
R-HSA-2262752	Cellular responses to stress
R-HSA-2555396	Mitotic Metaphase and Anaphase
R-HSA-2559583	Cellular Senescence
R-HSA-2559586	DNA Damage/Telomere Stress Induced Senescence
R-HSA-2995410	Nuclear Envelope (NE) Reassembly
R-HSA-447115	Interleukin-12 family signaling
R-HSA-449147	Signaling by Interleukins
R-HSA-5357801	Programmed Cell Death
R-HSA-68875	Mitotic Prophase
R-HSA-68882	Mitotic Anaphase

MSigDB gene sets: 634 (showing top): MODULE_52, HORIUCHI_WTAP_TARGETS_DN, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, KANG_DOXORUBICIN_RESISTANCE_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, REACTOME_MEIOTIC_SYNAPSIS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GCM_PPM1D, MODULE_16, GNF2_MCM5, KONG_E2F3_TARGETS, GNF2_RRM2, GOLDRATH_ANTIGEN_RESPONSE

GO Biological Process (6): nuclear envelope organization (GO:0006998), nuclear migration (GO:0007097), heterochromatin formation (GO:0031507), nuclear pore localization (GO:0051664), protein localization to nuclear envelope (GO:0090435), cytoskeleton organization (GO:0007010)

GO Molecular Function (6): structural constituent of cytoskeleton (GO:0005200), phospholipase binding (GO:0043274), structural constituent of nuclear lamina (GO:0160123), sequence-specific double-stranded DNA binding (GO:1990837), double-stranded DNA binding (GO:0003690), protein binding (GO:0005515)

GO Cellular Component (11): nucleus (GO:0005634), nuclear envelope (GO:0005635), nuclear inner membrane (GO:0005637), lamin filament (GO:0005638), nuclear lamina (GO:0005652), nucleoplasm (GO:0005654), membrane (GO:0016020), nuclear matrix (GO:0016363), nuclear membrane (GO:0031965), intermediate filament (GO:0005882), nuclear periphery (GO:0034399)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
RHO GTPase cycle	2
Meiosis	1
DNA Damage/Telomere Stress Induced Senescence	1
Mitotic Prophase	1
Nuclear Envelope (NE) Reassembly	1
Apoptotic cleavage of cellular proteins	1
Nuclear Envelope Breakdown	1
Neurodegenerative Diseases	1
Interleukin-12 signaling	1
Programmed Cell Death	1
Apoptotic execution phase	1
Immune System	1
Reproduction	1
Cell Cycle	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
nuclear lumen	3
nucleus organization	2
structural molecule activity	2
nucleus	2
nuclear envelope	2
endomembrane system organization	1
membrane organization	1
intracellular transport	1
nucleus localization	1
establishment of organelle localization	1
cellular component assembly	1
heterochromatin boundary formation	1
negative regulation of gene expression, epigenetic	1
heterochromatin organization	1
protein-containing complex localization	1
localization within membrane	1
protein localization to nucleus	1
organelle organization	1
cytoskeleton	1
cytoskeleton organization	1
enzyme binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
DNA binding	1
binding	1
intracellular membrane-bounded organelle	1
endomembrane system	1
organelle envelope	1
organelle inner membrane	1
nuclear membrane	1
nuclear lamina	1
intermediate filament	1
nuclear periphery	1
organelle membrane	1
intermediate filament cytoskeleton	1
polymeric cytoskeletal fiber	1

Protein interactions and networks

STRING

4172 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LMNB1	LBR	Q14739	998
LMNB1	EMD	P50402	984
LMNB1	LMNB2	Q03252	964
LMNB1	TMPO	P08918	905
LMNB1	SUN1	O94901	894
LMNB1	MNS1	Q8NEH6	841
LMNB1	ERBIN	Q96RT1	818
LMNB1	SYNE2	Q8WXH0	816
LMNB1	ACTB	P02570	803
LMNB1	BANF1	O75531	790
LMNB1	SYNE1	Q8NF91	785
LMNB1	BANF2	Q9H503	782
LMNB1	GAPDH	P00354	781
LMNB1	ZMPSTE24	O75844	774
LMNB1	LEMD3	Q9Y2U8	772

IntAct

258 interactions, top by confidence:

A	B	Type	Score
LMNA	LMNB1	psi-mi:“MI:2364”(proximity)	0.930
LMNA	LMNB1	psi-mi:“MI:0915”(physical association)	0.930
LMNB1	LMNA	psi-mi:“MI:0915”(physical association)	0.930
LMNB2	LMNB1	psi-mi:“MI:0915”(physical association)	0.850
LMNB1	LMNB2	psi-mi:“MI:0915”(physical association)	0.850
LMNB1	KPNA1	psi-mi:“MI:0915”(physical association)	0.740
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
LMNA	LMNB1	psi-mi:“MI:0914”(association)	0.680
LMNB1	LMNA	psi-mi:“MI:0915”(physical association)	0.680
MAP1LC3B	LMNB1	psi-mi:“MI:0915”(physical association)	0.680
MAP1LC3B	LMNB1	psi-mi:“MI:0914”(association)	0.680
MAP1LC3B	LMNB1	psi-mi:“MI:0407”(direct interaction)	0.680

BioGRID (796): LMNB1 (Affinity Capture-Western), LMNB1 (Affinity Capture-MS), LMNB1 (Affinity Capture-MS), LMNB1 (Affinity Capture-MS), LMNB1 (Affinity Capture-MS), LMNB1 (Affinity Capture-MS), LMNB1 (Affinity Capture-MS), LMNB1 (Affinity Capture-MS), LMNB1 (Affinity Capture-MS), KPNA4 (Co-fractionation), LMNB1 (Co-fractionation), RPA1 (Co-fractionation), RPA3 (Co-fractionation), SF3B3 (Co-fractionation), SRSF6 (Co-fractionation)

ESM2 similar proteins: A1KQY9, A5A6M0, O02365, O57607, O57611, P05781, P05783, P05784, P05786, P05787, P08728, P08776, P08778, P08802, P08928, P09010, P09654, P10999, P11048, P11679, P14731, P14732, P14733, P19001, P20700, P21910, P23730, P23731, P25030, P51856, P70615, P90900, Q01240, Q01241, Q03427, Q04695, Q07427, Q10758, Q19286, Q19289

Diamond homologs: A0A125S9M6, A6QQJ3, O76011, O77788, P02542, P02545, P04260, P04261, P04263, P05785, P07197, P08552, P08553, P08928, P09010, P10999, P11048, P12839, P13648, P14731, P14732, P14733, P15331, P16053, P16275, P20700, P21619, P21807, P21910, P23239, P23565, P35616, P41219, P46660, P48671, P48672, P48678, P48679, P70615, Q02916

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PRKCB	unknown	LMNB1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 112 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
RHOQ GTPase cycle	5	13.3×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
autophagosome maturation	7	27.3×	5e-06
cellular response to starvation	6	12.9×	2e-03
autophagosome assembly	5	12.5×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

334 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	12
Likely pathogenic	2
Uncertain significance	180
Likely benign	60
Benign	42

Top pathogenic / likely-pathogenic (14)

Variant ID	HGVS	Classification
1460260	NC_000005.9:g.(?126113201)(126253863_?)dup	Pathogenic
147781	GRCh38/hg38 5q23.2(chr5:126657759-126923623)x3	Pathogenic
3251581	NC_000005.9:g.(?126112827)(126172713_?)dup	Pathogenic
3343965	NM_005573.4(LMNB1):c.97_99del (p.Lys33del)	Pathogenic
442081	GRCh37/hg19 5q23.2(chr5:126002101-126341594)x3	Pathogenic
442450	GRCh37/hg19 5q23.2(chr5:126002101-126351612)x3	Pathogenic
813713	NM_005573.4(LMNB1):c.1091T>C (p.Leu364Pro)	Pathogenic
915454	NM_005573.4(LMNB1):c.455C>G (p.Ala152Gly)	Pathogenic
915455	NM_005573.4(LMNB1):c.97A>G (p.Lys33Glu)	Pathogenic
915456	NM_005573.4(LMNB1):c.124C>T (p.Arg42Trp)	Pathogenic
915457	NM_005573.4(LMNB1):c.939+1G>A	Pathogenic
915458	NM_005573.4(LMNB1):c.939+2362_1491+560del	Pathogenic
2444231	NM_005573.4(LMNB1):c.814-1G>T	Likely pathogenic
997433	NM_005573.4(LMNB1):c.269G>C (p.Arg90Pro)	Likely pathogenic

SpliceAI

2276 predictions. Top by Δscore:

Variant	Effect	Δscore
5:126777868:G:GG	donor_gain	1.0000
5:126804764:A:G	acceptor_gain	1.0000
5:126804774:A:AG	acceptor_gain	1.0000
5:126804775:G:GA	acceptor_gain	1.0000
5:126804775:GCT:G	acceptor_gain	1.0000
5:126804775:GCTAT:G	acceptor_gain	1.0000
5:126804930:CAGG:C	donor_loss	1.0000
5:126804933:G:GG	donor_gain	1.0000
5:126804933:GT:G	donor_loss	1.0000
5:126804934:T:G	donor_loss	1.0000
5:126805563:T:A	acceptor_gain	1.0000
5:126805566:A:AG	acceptor_gain	1.0000
5:126805567:A:G	acceptor_gain	1.0000
5:126805569:A:AG	acceptor_gain	1.0000
5:126805569:AGTT:A	acceptor_gain	1.0000
5:126805570:G:GA	acceptor_gain	1.0000
5:126805570:GTT:G	acceptor_gain	1.0000
5:126805570:GTTG:G	acceptor_gain	1.0000
5:126805694:G:GT	donor_gain	1.0000
5:126805694:GAG:G	donor_gain	1.0000
5:126805694:GAGG:G	donor_loss	1.0000
5:126805695:AG:A	donor_loss	1.0000
5:126805696:GG:G	donor_loss	1.0000
5:126805697:GTAA:G	donor_loss	1.0000
5:126805698:T:A	donor_loss	1.0000
5:126810321:G:GT	donor_gain	1.0000
5:126810351:G:GG	donor_gain	1.0000
5:126811769:TTAG:T	acceptor_loss	1.0000
5:126811771:A:AG	acceptor_gain	1.0000
5:126811771:AGCTT:A	acceptor_gain	1.0000

AlphaMissense

3836 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:126819070:T:C	L363P	1.000
5:126819091:T:C	L370P	1.000
5:126819121:T:C	L380P	1.000
5:126819124:T:C	L381S	1.000
5:126777615:T:C	L36P	0.999
5:126777624:T:A	L39H	0.999
5:126777624:T:C	L39P	0.999
5:126777633:G:C	R42P	0.999
5:126777636:T:C	L43P	0.999
5:126819073:T:C	L364P	0.999
5:126819081:A:G	K367E	0.999
5:126819091:T:A	L370Q	0.999
5:126819099:G:A	E373K	0.999
5:126819100:A:G	E373G	0.999
5:126819100:A:T	E373V	0.999
5:126819101:A:C	E373D	0.999
5:126819101:A:T	E373D	0.999
5:126819103:T:G	I374S	0.999
5:126819108:G:C	A376P	0.999
5:126819111:T:C	Y377H	0.999
5:126819111:T:G	Y377D	0.999
5:126819121:T:A	L380H	0.999
5:126819125:A:C	L381F	0.999
5:126819125:A:T	L381F	0.999
5:126819142:G:C	R387T	0.999
5:126819142:G:T	R387M	0.999
5:126820910:G:C	R387S	0.999
5:126820910:G:T	R387S	0.999
5:126820912:T:C	L388S	0.999
5:126826057:T:A	W521R	0.999

dbSNP variants (sampled 300 via entrez): RS1000014277 (5:126828673 C>T), RS1000103193 (5:126816266 G>T), RS1000148176 (5:126775490 T>C), RS1000169878 (5:126792640 G>A), RS1000227622 (5:126832550 T>A,G), RS1000230607 (5:126823651 G>A), RS1000261284 (5:126801363 C>A,T), RS1000306241 (5:126784162 T>C), RS1000465610 (5:126790398 A>G), RS1000468550 (5:126832364 A>G), RS1000526083 (5:126790704 C>G), RS1000561492 (5:126834071 A>C), RS1000616916 (5:126827272 G>A), RS1000643326 (5:126785987 C>T), RS1000688412 (5:126825607 G>A,C)

Disease associations

OMIM: gene MIM:150340 | disease phenotypes: MIM:169500, MIM:619179

GenCC curated gene-disease

Disease	Classification	Inheritance
microcephaly 26, primary, autosomal dominant	Definitive	Autosomal dominant
adult-onset autosomal dominant demyelinating leukodystrophy	Strong	Autosomal dominant
leukodystrophy, demyelinating, adult-onset, autosomal dominant, typical	Strong	Autosomal dominant
leukodystrophy, demyelinating, adult-onset, autosomal dominant, atypical	Strong	Autosomal dominant
microcephaly	Strong	Autosomal dominant
autosomal dominant primary microcephaly	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
microcephaly 26, primary, autosomal dominant	Definitive	AD

Mondo (6): adult-onset autosomal dominant demyelinating leukodystrophy (MONDO:0008215), microcephaly 26, primary, autosomal dominant (MONDO:0030928), microcephaly (MONDO:0001149), autosomal dominant primary microcephaly (MONDO:0007988), leukodystrophy, demyelinating, adult-onset, autosomal dominant, typical (MONDO:0700295), leukodystrophy, demyelinating, adult-onset, autosomal dominant, atypical (MONDO:0700286)

Orphanet (2): Adult-onset autosomal dominant leukodystrophy (Orphanet:99027), Syndrome with microcephaly as a major feature (Orphanet:269528)

HPO phenotypes

106 total (30 of 106 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000012	Urinary urgency
HP:0000016	Urinary retention
HP:0000126	Hydronephrosis
HP:0000212	Gingival overgrowth
HP:0000243	Trigonocephaly
HP:0000252	Microcephaly
HP:0000307	Pointed chin
HP:0000316	Hypertelorism
HP:0000341	Narrow forehead
HP:0000343	Long philtrum
HP:0000407	Sensorineural hearing impairment
HP:0000411	Protruding ear
HP:0000426	Prominent nasal bridge
HP:0000431	Wide nasal bridge
HP:0000496	Abnormality of eye movement
HP:0000582	Upslanted palpebral fissure
HP:0000637	Long palpebral fissure
HP:0000639	Nystagmus
HP:0000666	Horizontal nystagmus
HP:0000708	Atypical behavior
HP:0000726	Dementia
HP:0000750	Delayed speech and language development
HP:0000802	Impotence
HP:0000970	Anhidrosis
HP:0001137	Alternating esotropia
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001257	Spasticity

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001546_2	Parkinson’s disease (motor and cognition)	5.000000e-06
GCST006585_2848	Blood protein levels	3.000000e-09
GCST009531_5	Body fat percentage	1.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007800	body fat percentage

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
C566813	Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant (supp.)
C537323	Microcephaly autosomal dominant (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725026 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

3 potent at pChembl≥5 of 5 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.38	Kd	420.1	nM	CHEMBL5653589
6.38	ED50	420.1	nM	CHEMBL5653589
6.36	IC50	440	nM	MOLIBRESIB

PubChem BioAssay actives

2 with measured affinity, of 10 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148606: Binding affinity to human LMNB1 incubated for 45 mins by Kinobead based pull down assay	kd	0.4201	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178968: Inhibition of LMNB1 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.4400	uM

CTD chemical–gene interactions

147 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	9
bisphenol A	affects expression, decreases expression, increases expression	5
Benzo(a)pyrene	affects expression, decreases expression	5
Estradiol	decreases expression, decreases phosphorylation, increases expression	4
Tretinoin	decreases expression, increases expression	4
Valproic Acid	affects expression, decreases expression	4
Cyclosporine	decreases expression	4
Cadmium Chloride	decreases expression, increases cleavage, increases expression	4
Air Pollutants	decreases expression, affects cotreatment, increases abundance, increases oxidation	3
Doxorubicin	decreases expression, decreases phosphorylation, affects response to substance	3
Quercetin	decreases expression, increases expression	3
Particulate Matter	decreases expression, increases abundance, affects cotreatment	3
trichostatin A	affects expression, decreases expression	2
arsenite	decreases reaction, increases reaction, affects expression, affects binding	2
cobaltous chloride	decreases expression	2
cupric oxide	decreases expression	2
epigallocatechin gallate	affects cotreatment, decreases expression	2
bisphenol S	increases methylation, increases expression	2
Dasatinib	decreases expression, decreases reaction	2
Resveratrol	affects cotreatment, increases expression, increases cleavage	2
Zoledronic Acid	decreases expression, increases expression	2
Acetaminophen	decreases expression, increases degradation	2
Caffeine	affects phosphorylation, decreases expression	2
Copper	affects binding, decreases expression	2
Fluorouracil	decreases expression, affects response to substance	2
Hydrogen Peroxide	decreases reaction, affects expression, decreases expression	2
Lovastatin	affects localization, decreases farnesylation, increases degradation	2
Nickel	increases expression	2
Ozone	affects cotreatment, increases oxidation, increases abundance, decreases expression, increases expression	2
Tobacco Smoke Pollution	decreases expression	2

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651648	Binding	Binding affinity to human LMNB1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

8 cell lines: 8 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1VZ	Abcam HeLa LMNB1 KO	Cancer cell line	Female
CVCL_B7Y1	Abcam Raji LMNB1 KO	Cancer cell line	Male
CVCL_B9YR	Abcam THP-1 LMNB1 KO	Cancer cell line	Male
CVCL_C7AI	Abcam PC-3 LMNB1 KO	Cancer cell line	Male
CVCL_SV66	HAP1 LMNB1 (-) 1	Cancer cell line	Male
CVCL_SV67	HAP1 LMNB1 (-) 2	Cancer cell line	Male
CVCL_SV68	HAP1 LMNB1 (-) 3	Cancer cell line	Male
CVCL_UR41	HeLa Kyoto EGFP-LaminB1/H2B-mCherry	Cancer cell line	Female

Clinical trials (associated diseases)

19 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT02699190	Not specified	COMPLETED	LeukoSEQ: Whole Genome Sequencing as a First-Line Diagnostic Tool for Leukodystrophies
NCT03047369	Not specified	RECRUITING	The Myelin Disorders Biorepository Project
NCT05518188	PHASE1/PHASE2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT00001639	Not specified	COMPLETED	Evaluation of Patients With Unresolved Chromosome Abnormalities
NCT01151462	Not specified	WITHDRAWN	Postnatal HCMV Infection in Very Preterm Infants. Implications, Morbidity, Growth and Neurodevelopmental Outcomes.
NCT01565005	Not specified	COMPLETED	Microcephaly Genetic Deficiency in Neural Progenitors
NCT02510170	Not specified	COMPLETED	Fetal and Maternal Head Circumference During Pregnancy in Israeli Population
NCT02741882	Not specified	COMPLETED	Zika and Microcephaly: Case-control Study
NCT02943304	Not specified	COMPLETED	Neurodevelopment Outcome of Newborns Exposed to Zika Virus (ZIKV) in Utero
NCT03255369	Not specified	UNKNOWN	Vertical Exposure to Zika Virus and Its Consequences for Child Neurodevelopment (ZIKVIRUSIFF)
NCT03325946	Not specified	RECRUITING	The FBRI VTC Neuromotor Research Clinic
NCT03330600	Not specified	COMPLETED	Efficacy of Aquatic Physiotherapy in Children With Microcephaly by Zika Virus Congenital Syndrome
NCT03548779	Not specified	COMPLETED	North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2
NCT03651687	Not specified	COMPLETED	Guangzhou Surveillance and Clinical Study in Microcephaly (GSCSM)
NCT03922594	Not specified	TERMINATED	Surveillance of Zika-related Microcephaly in Sub-Saharan Africa and Asia
NCT04816175	Not specified	COMPLETED	Intensive Therapy for Children With Microcephaly, Hyperkinetic Movements, or Global Developmental Delay
NCT05322980	Not specified	COMPLETED	Summary of Infants Weighing 500 Grams or Less
NCT06019182	Not specified	RECRUITING	MEHMO Natural History and Biomarkers
NCT06566066	Not specified	RECRUITING	Register for Patients With Thyroid Hormone Resistance.