LMNB2

Summary

LMNB2 (lamin B2, HGNC:6638) is a protein-coding gene on chromosome 19p13.3, encoding Lamin-B2 (Q03252). 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 a B type nuclear lamin. The nuclear lamina consists of a two-dimensional matrix of proteins located next to the inner nuclear membrane. The lamin family of proteins make up the matrix and are highly conserved in evolution. During mitosis, the lamina matrix is reversibly disassembled as the lamin proteins are phosphorylated. Lamin proteins are thought to be involved in nuclear stability, chromatin structure and gene expression. Vertebrate lamins consist of two types, A and B. Mutations in this gene are associated with acquired partial lipodystrophy.

Source: NCBI Gene 84823 — RefSeq curated summary.

At a glance

• Gene–disease (curated): progressive myoclonic epilepsy type 9 (Strong, GenCC) — +4 more curated relationships
• Clinical variants (ClinVar): 686 total — 4 pathogenic
• Phenotypes (HPO): 66
• Druggable target: yes
• MANE Select transcript: NM_032737

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6638
Approved symbol	LMNB2
Name	lamin B2
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000176619
Ensembl biotype	protein_coding
OMIM	150341
Entrez	84823

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 9 protein_coding, 4 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000325327, ENST00000475819, ENST00000490554, ENST00000527409, ENST00000532465, ENST00000534495, ENST00000867388, ENST00000867389, ENST00000917221, ENST00000917222, ENST00000917223, ENST00000917224, ENST00000917225, ENST00000917226

RefSeq mRNA: 1 — MANE Select: NM_032737 NM_032737

CCDS: CCDS12090

Canonical transcript exons

ENST00000325327 — 12 exons

Exon	Start	End
ENSE00000655672	2438163	2438288
ENSE00001052208	2444404	2444540
ENSE00001150160	2438375	2438531
ENSE00001150172	2456670	2456959
ENSE00001247707	2428166	2430952
ENSE00003466453	2431548	2431658
ENSE00003489516	2434295	2434515
ENSE00003497284	2432416	2432523
ENSE00003539631	2434788	2434913
ENSE00003563021	2435001	2435171
ENSE00003588969	2433826	2434105
ENSE00003594665	2431783	2431902

Expression profiles

Bgee: expression breadth ubiquitous, 194 present calls, max score 97.24.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.0023 / max 234.9255, expressed in 1815 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
178172	35.3543	1814
178171	1.4369	857
178169	0.1916	72
178170	0.0195	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	97.24	gold quality
left testis	UBERON:0004533	95.73	gold quality
right testis	UBERON:0004534	95.62	gold quality
ganglionic eminence	UBERON:0004023	94.82	gold quality
endometrium epithelium	UBERON:0004811	94.78	gold quality
embryo	UBERON:0000922	94.43	gold quality
secondary oocyte	CL:0000655	93.89	gold quality
stromal cell of endometrium	CL:0002255	93.22	gold quality
testis	UBERON:0000473	92.33	gold quality
mucosa of transverse colon	UBERON:0004991	90.95	gold quality
esophagus mucosa	UBERON:0002469	90.17	gold quality
lower esophagus mucosa	UBERON:0035834	90.13	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.53	gold quality
gastrocnemius	UBERON:0001388	89.34	gold quality
apex of heart	UBERON:0002098	88.84	gold quality
muscle of leg	UBERON:0001383	88.70	gold quality
gingival epithelium	UBERON:0001949	88.10	silver quality
oocyte	CL:0000023	87.81	gold quality
cortical plate	UBERON:0005343	87.76	gold quality
right hemisphere of cerebellum	UBERON:0014890	87.41	gold quality
cerebellar hemisphere	UBERON:0002245	86.82	gold quality
esophagus squamous epithelium	UBERON:0006920	86.79	gold quality
cerebellar cortex	UBERON:0002129	86.76	gold quality
epithelium of esophagus	UBERON:0001976	86.34	gold quality
left adrenal gland	UBERON:0001234	86.25	gold quality
right adrenal gland	UBERON:0001233	86.09	gold quality
left adrenal gland cortex	UBERON:0035825	85.98	gold quality
right atrium auricular region	UBERON:0006631	85.78	gold quality
adenohypophysis	UBERON:0002196	85.71	gold quality
esophagus	UBERON:0001043	85.68	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.31

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

72 targeting LMNB2, 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-3163	100.00	77.23	8605
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4320	99.75	65.80	793
HSA-MIR-1255A	99.74	68.09	744
HSA-MIR-1255B-5P	99.74	68.16	741
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-6887-3P	99.66	67.83	1778

Literature-anchored findings (GeneRIF, showing 23)

• analysis of protein-DNA interactions at the human lamin B2 replication origin (PMID:12902329)
• The proteins bound in vivo at the LMNB2 replication origin were investigated along the cell cycle. (PMID:12912926)
• This analysis reveals the modular structure of the lamin B2 origin and supports the idea that sequence elements close to the replication start site play an important role in origin activation. (PMID:15024083)
• the distinctive ensemble of heterotypic lamin interactions in a particular cell type affects the stability of the lamin polymer (PMID:15284226)
• the lamin B2 origin adopts a structure partly composed of intramolecular TAT triads (PMID:15611042)
• 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)
• Three new rare heterozygous mutations are the first reported for LMNB2 and are the first reported among patients with acquired partial lipodystrophy. (PMID:16826530)
• human lamin B(2) is indeed synthesized as a longer version than previously reported, because it contains these additional 20 amino acids (PMID:17070523)
• The human DNA replication origin, located in the lamin B2 gene, interacts with the DNA topoisomerases I and II in a cell cycle-modulated manner. (PMID:17290216)
• Using shotgun mass spectrometry, we found this protein differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19165527)
• 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)
• Studies indicate that the lamin-binding proteins implicated in laminopathies include lamin B2 and nuclear envelope proteins. (PMID:21400569)
• Mutation in LMNB2 gene is associated with partial lipodystrophy. (PMID:22768673)
• 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)
• Nuclear envelope remodelling during human spermiogenesis involves somatic B-type lamins and a spermatid-specific B3 lamin isoform. (PMID:25477337)
• Mutation of the nuclear lamin gene LMNB2 in progressive myoclonus epilepsy with early ataxia. (PMID:25954030)
• our studies strongly implicate an overarching role for Lamin B2 in the maintenance of nuclear architecture since loss of Lamin B2 relieves the spatial positional constraints required for maintaining conserved localization of aneuploid chromosome territories in the interphase nucleus. (PMID:26921073)
• Lamin B2 promotes the malignant phenotype of non-small cell lung cancer cells by upregulating dimethylation of histone 3 lysine 9. (PMID:32416090)
• Heterozygous lamin B1 and lamin B2 variants cause primary microcephaly and define a novel laminopathy. (PMID:33033404)
• LMNB2 is a prognostic biomarker and correlated with immune infiltrates in hepatocellular carcinoma. (PMID:33211382)
• LMNB2 promotes the progression of colorectal cancer by silencing p21 expression. (PMID:33782407)
• Lamin B2 contributes to the proliferation of bladder cancer cells via activating the expression of cell division cycleassociated protein 3. (PMID:35775376)
• The role of lamin B2 in human diseases. (PMID:37044185)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lmnb2	ENSDARG00000101624
mus_musculus	Lmnb2	ENSMUSG00000062075
rattus_norvegicus	Lmnb2	ENSRNOG00000025742

Paralogs (68): KRT33A (ENSG00000006059), VIM (ENSG00000026025), KRT31 (ENSG00000094796), NEFM (ENSG00000104722), KRT23 (ENSG00000108244), KRT37 (ENSG00000108417), KRT32 (ENSG00000108759), KRT18 (ENSG00000111057), LMNB1 (ENSG00000113368), 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)

Protein

Protein identifiers

Lamin-B2 — Q03252 (reviewed: Q03252)

All UniProt accessions (1): Q03252

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. Dimer. 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 TMEM43.

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-37 and Ser-407 at the onset of mitosis drives lamin disassembly and nuclear envelope breakdown.

Disease relevance. 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. Intellectual disability in some cases. APLD is a sporadic disorder of unknown etiology. The disease is caused by variants affecting the gene represented in this entry. Epilepsy, progressive myoclonic 9 (EPM9) [MIM:616540] A form of progressive myoclonic epilepsy, a clinically and genetically heterogeneous group of disorders defined by the combination of action and reflex myoclonus, other types of epileptic seizures, and progressive neurodegeneration and neurocognitive impairment. EPM9 is an autosomal recessive form characterized by myoclonus, tonic-clonic seizures, ataxia, and delayed psychomotor development. The disease may be caused by variants affecting the gene represented in this entry. Microcephaly 27, primary, autosomal dominant (MCPH27) [MIM:619180] 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. MCPH27 is an autosomal dominant form apparent in early childhood and associated with global developmental delay, delayed walking, inability to walk, impaired intellectual development, and poor or absent speech. Brain imaging may show enlarged ventricles or gyral abnormalities 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 (1): NP_116126* (*=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 (60 total): modified residue 13, region of interest 10, strand 10, sequence variant 7, cross-link 5, compositionally biased region 4, domain 2, sequence conflict 2, chain 1, propeptide 1, short sequence motif 1, lipid moiety-binding region 1, glycosylation site 1, helix 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
5BNW	X-RAY DIFFRACTION	2.4
2LLL	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q03252-F1	79.82	0.62

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 (19): 23, 34, 37, 81, 316, 407, 420, 422, 424, 426, 433, 497, 617, 617, 77, 81, 195, 255, 489

Glycosylation sites (1): 413

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 376 (showing top): MORF_DNMT1, MODULE_52, HORIUCHI_WTAP_TARGETS_DN, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, MORF_ESPL1, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GEORGES_CELL_CYCLE_MIR192_TARGETS, MORF_RRM1, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, MODULE_16, PATIL_LIVER_CANCER, PUJANA_CHEK2_PCC_NETWORK, MODULE_118, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC

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 (3): structural constituent of cytoskeleton (GO:0005200), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (5): nuclear lamina (GO:0005652), intermediate filament (GO:0005882), nuclear membrane (GO:0031965), nucleus (GO:0005634), nuclear envelope (GO:0005635)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nucleus organization	2
nuclear envelope	2
nucleus	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
structural molecule activity	1
cytoskeleton	1
cytoskeleton organization	1
protein binding	1
binding	1
nuclear periphery	1
cellular anatomical structure	1
intermediate filament cytoskeleton	1
polymeric cytoskeletal fiber	1
organelle membrane	1
intracellular membrane-bounded organelle	1
endomembrane system	1
organelle envelope	1

Protein interactions and networks

STRING

3056 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LMNB2	LBR	Q14739	998
LMNB2	LMNB1	P20700	964
LMNB2	EMD	P50402	859
LMNB2	TIMM13	P62206	851
LMNB2	SUN1	O94901	842
LMNB2	SENP2	Q9HC62	768
LMNB2	LEMD3	Q9Y2U8	758
LMNB2	BANF1	O75531	751
LMNB2	ACTB	P02570	742
LMNB2	GAPDH	P00354	709
LMNB2	TM7SF2	O76062	671
LMNB2	RGPD1	P0C839	660
LMNB2	TMPO	P08918	658
LMNB2	SENP3	Q9H4L4	654
LMNB2	LMNA	P02545	652

IntAct

189 interactions, top by confidence:

A	B	Type	Score
PALB2	BRCA2	psi-mi:“MI:0914”(association)	0.970
PDE6D	ARL3	psi-mi:“MI:0914”(association)	0.920
LMNB2	LMNB1	psi-mi:“MI:0915”(physical association)	0.850
LMNA	LMNB2	psi-mi:“MI:0915”(physical association)	0.850
LMNB1	LMNB2	psi-mi:“MI:0915”(physical association)	0.850
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
LMNA	LMNB1	psi-mi:“MI:0914”(association)	0.680
LMNB1	LMNA	psi-mi:“MI:0914”(association)	0.680
LRRK2	LMNB1	psi-mi:“MI:0915”(physical association)	0.620
LMNB2	ZC2HC1C	psi-mi:“MI:0915”(physical association)	0.560
LMNB2	GOLGA2	psi-mi:“MI:0915”(physical association)	0.560
LMNB2	CCDC120	psi-mi:“MI:0915”(physical association)	0.560
LMNB2	WASHC3	psi-mi:“MI:0915”(physical association)	0.560
USP2	LMNB2	psi-mi:“MI:0915”(physical association)	0.560
CCDC88B	LMNB2	psi-mi:“MI:0915”(physical association)	0.560
LMNB2	ZFHX3	psi-mi:“MI:0915”(physical association)	0.560
LMNB2	LMNB2	psi-mi:“MI:0915”(physical association)	0.560
CA8	LMNB2	psi-mi:“MI:0915”(physical association)	0.560
TRIM27	LMNB2	psi-mi:“MI:0915”(physical association)	0.560
LMNB2	CDC37	psi-mi:“MI:0915”(physical association)	0.560
LMNB2	TP53BP2	psi-mi:“MI:0915”(physical association)	0.560
LMNB2	THAP1	psi-mi:“MI:0915”(physical association)	0.560
LMNB2	LZTS1	psi-mi:“MI:0915”(physical association)	0.560
POU6F2	LMNB2	psi-mi:“MI:0915”(physical association)	0.560
LMNB2	MID2	psi-mi:“MI:0915”(physical association)	0.560
LMNB2	PPP1R13B	psi-mi:“MI:0915”(physical association)	0.560
LMNB2	AMOTL2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (317): LMNB2 (Affinity Capture-MS), LMNB2 (Affinity Capture-MS), LMNB2 (Affinity Capture-MS), LMNB2 (Affinity Capture-MS), LMNB2 (Affinity Capture-MS), LMNB2 (Affinity Capture-MS), LMNB2 (Affinity Capture-MS), LMNB2 (Affinity Capture-MS), LMNB2 (Affinity Capture-MS), LMNB2 (Affinity Capture-MS), LMNB2 (Two-hybrid), SOX4 (Affinity Capture-Western), LMNB2 (Co-fractionation), MAPK1 (Co-fractionation), MAPK3 (Co-fractionation)

ESM2 similar proteins: A0A125S9M5, A0A8C0N8E3, A6QQJ3, O62654, P02540, P02541, P02543, P02544, P02545, P03995, P08670, P08928, P09010, P10999, P11048, P13648, P14136, P14731, P14732, P14733, P15331, P17661, P20152, P20700, P21619, P21807, P21910, P31000, P31001, P35617, P41219, P47819, P48616, P48670, P48675, P48676, P48678, P48679, P70615, P84198

Diamond homologs: A0A125S9M6, A0JND2, A4FUZ0, A5A6M8, A6NCN2, A7YWK3, O43790, P02542, P02545, P02547, P02548, P04104, P04260, P04261, P04262, P04263, P07196, P07744, P08551, P08928, P09010, P10999, P12035, P12036, P13647, P13648, P15241, P16884, P19013, P19246, P19527, P21619, P21910, P25691, P35908, P48671, P48672, P48678, P48679, P78385

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 138 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
Intrinsic Pathway for Apoptosis	5	16.3×	2e-03
Apoptosis	7	13.1×	3e-04
Programmed Cell Death	8	13.0×	9e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	310
Likely benign	270
Benign	57

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
208980	NM_032737.4(LMNB2):c.469C>T (p.His157Tyr)	Pathogenic
3366973	NM_032737.4(LMNB2):c.578_579del (p.Val193fs)	Pathogenic
997434	NM_032737.4(LMNB2):c.1192G>A (p.Glu398Lys)	Pathogenic
997435	NM_032737.4(LMNB2):c.160A>C (p.Asn54His)	Pathogenic

SpliceAI

1639 predictions. Top by Δscore:

Variant	Effect	Δscore
19:2431542:TCCTA:T	donor_loss	1.0000
19:2431543:CCTAC:C	donor_loss	1.0000
19:2431544:CTA:C	donor_loss	1.0000
19:2431545:TA:T	donor_loss	1.0000
19:2431546:A:C	donor_loss	1.0000
19:2431547:CC:C	donor_loss	1.0000
19:2431655:CTTC:C	acceptor_gain	1.0000
19:2431657:TCCTG:T	acceptor_loss	1.0000
19:2431658:CCTG:C	acceptor_gain	1.0000
19:2431659:CTGTG:C	acceptor_loss	1.0000
19:2432413:TA:T	donor_loss	1.0000
19:2432414:ACC:A	donor_loss	1.0000
19:2432521:ATCC:A	acceptor_loss	1.0000
19:2432523:CCTG:C	acceptor_loss	1.0000
19:2433817:T:A	donor_gain	1.0000
19:2434102:CAGC:C	acceptor_gain	1.0000
19:2434104:GC:G	acceptor_gain	1.0000
19:2434105:CC:C	acceptor_gain	1.0000
19:2434106:C:CA	acceptor_loss	1.0000
19:2434106:C:CC	acceptor_gain	1.0000
19:2434261:A:AC	donor_gain	1.0000
19:2434262:C:CC	donor_gain	1.0000
19:2434262:CT:C	donor_gain	1.0000
19:2434279:T:TA	donor_gain	1.0000
19:2434290:CGCA:C	donor_loss	1.0000
19:2434291:GCA:G	donor_loss	1.0000
19:2434292:CACCT:C	donor_loss	1.0000
19:2434293:A:AT	donor_loss	1.0000
19:2434294:CCT:C	donor_gain	1.0000
19:2434298:T:A	donor_gain	1.0000

AlphaMissense

4026 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:2434322:C:G	R392P	0.999
19:2434346:A:G	L384P	0.999
19:2434367:A:G	L377P	0.999
19:2434316:A:G	L394P	0.998
19:2456764:A:G	L57P	0.998
19:2456767:C:G	R56P	0.998
19:2456773:T:A	N54I	0.998
19:2456776:A:G	L53P	0.998
19:2456785:A:G	L50P	0.998
19:2431833:A:G	W554R	0.997
19:2431833:A:T	W554R	0.997
19:2432456:A:G	F517S	0.997
19:2456752:A:T	I61N	0.997
19:2456772:G:C	N54K	0.997
19:2456772:G:T	N54K	0.997
19:2456776:A:T	L53H	0.997
19:2434329:C:G	A390P	0.996
19:2434336:C:A	E387D	0.996
19:2434336:C:G	E387D	0.996
19:2444494:C:G	R104P	0.996
19:2456734:A:G	L67P	0.996
19:2431802:A:G	L564P	0.995
19:2433845:A:G	L488P	0.995
19:2434326:A:C	Y391D	0.995
19:2434337:T:A	E387V	0.995
19:2434337:T:C	E387G	0.995
19:2444506:A:G	L100P	0.995
19:2456740:C:G	R65P	0.995
19:2456746:C:G	R63P	0.995
19:2456764:A:T	L57Q	0.995

dbSNP variants (sampled 300 via entrez): RS1000021148 (19:2432088 C>T), RS1000221144 (19:2451141 T>A), RS1000223929 (19:2429542 G>A), RS1000249822 (19:2455422 G>A), RS1000471271 (19:2446619 T>C,G), RS1000486990 (19:2435980 C>T), RS1000520887 (19:2432064 G>A,C), RS1000706348 (19:2455639 C>A,G,T), RS1000727407 (19:2440189 T>C,G), RS1000819232 (19:2437361 G>A,C,T), RS1000828727 (19:2442234 T>C), RS1000889110 (19:2440479 C>T), RS1000899518 (19:2453305 A>C), RS1000912843 (19:2431264 C>G,T), RS1001001819 (19:2449160 G>A)

Disease associations

OMIM: gene MIM:150341 | disease phenotypes: MIM:616540, MIM:608709, MIM:619180

GenCC curated gene-disease

Disease	Classification	Inheritance
progressive myoclonic epilepsy type 9	Strong	Autosomal recessive
microcephaly 27, primary, autosomal dominant	Strong	Autosomal dominant
microcephaly	Moderate	Autosomal dominant
central nervous system malformation	Limited	Autosomal recessive
lipodystrophy, partial, acquired, susceptibility to	Limited	Autosomal dominant

Mondo (7): progressive myoclonic epilepsy type 9 (MONDO:0014685), lipodystrophy, partial, acquired, susceptibility to (MONDO:0100476), acquired partial lipodystrophy (MONDO:0012104), microcephaly 27, primary, autosomal dominant (MONDO:0030929), neurodevelopmental disorder (MONDO:0700092), central nervous system malformation (MONDO:0020022), microcephaly (MONDO:0001149)

Orphanet (2): Progressive myoclonic epilepsy type 9 (Orphanet:457265), Acquired partial lipodystrophy (Orphanet:79087)

HPO phenotypes

66 total (30 of 66 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000054	Micropenis
HP:0000093	Proteinuria
HP:0000100	Nephrotic syndrome
HP:0000147	Polycystic ovaries
HP:0000171	Microglossia
HP:0000243	Trigonocephaly
HP:0000365	Hearing impairment
HP:0000750	Delayed speech and language development
HP:0000790	Hematuria
HP:0000793	Membranoproliferative glomerulonephritis
HP:0000819	Diabetes mellitus
HP:0000855	Insulin resistance
HP:0001007	Hirsutism
HP:0001182	Tapered finger
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001274	Agenesis of corpus callosum
HP:0001336	Myoclonus
HP:0001382	Joint hypermobility
HP:0001397	Hepatic steatosis
HP:0001840	Metatarsus adductus
HP:0002066	Gait ataxia
HP:0002069	Bilateral tonic-clonic seizure
HP:0002119	Ventriculomegaly
HP:0002123	Generalized myoclonic seizure
HP:0002133	Status epilepticus

GWAS associations

0 associations (top):

MeSH disease descriptors (4)

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
D009421	Nervous System Malformations	C10.500; C16.131.666
D065886	Neurodevelopmental Disorders	F03.625
C562448	Lipodystrophy, Partial, Acquired (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5465302 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 3 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.79	Kd	1629	nM	CHEMBL5653589
5.79	ED50	1629	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 5 total; 1 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	2148657: Binding affinity to human LMNB2 incubated for 45 mins by Kinobead based pull down assay	kd	1.6292	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	5
bisphenol A	affects expression, decreases expression, increases expression, affects cotreatment	4
Benzo(a)pyrene	affects methylation, increases expression, increases mutagenesis	3
cobaltous chloride	decreases expression	2
Copper	affects binding, decreases expression	2
Tamoxifen	decreases expression, affects expression, affects cotreatment	2
Valproic Acid	affects expression, increases methylation	2
Cyclosporine	decreases expression, decreases methylation	2
Raloxifene Hydrochloride	affects expression, affects cotreatment, decreases expression	2
afuresertib	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
2,4,6-tribromophenol	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
methylselenic acid	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
decabromobiphenyl ether	increases expression	1
methylparaben	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
tetrabromobisphenol A	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
coumarin	decreases phosphorylation	1
cupric oxide	decreases expression	1
flavone	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5338472	Binding	Binding affinity to Lmnb2 (unknown origin) assessed as fold change in protein upregulation at 200 uM preincubated for 2 hrs followed by pronase addition and measured after 30 mins by coomassie blue staining based SDS-PAGE gel analysis	Structurally Diverse Alkaloids with Anti-Renal-Fibrosis Activity from the Centipede Scolopendra subspinipes mutilans. — J Nat Prod

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SV69	HAP1 LMNB2 (-) 1	Cancer cell line	Male
CVCL_XQ20	HAP1 LMNB2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
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.
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants