GeneBe

LMNB2

protein-coding

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

Gene summary

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. [provided by RefSeq, May 2012]

Previous symbols:
  • LMN2

MANE transcript

NM_032737.4

Inheritance

AD, AR

ClinVar variants

P:4U:306B:237

Top phenotype

Liopdystrophy, partial, acquired; Microcephaly 27, primary, autosomal dominant; Epilepsy, progressive myoclonic, 9

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr19:2,427,638-2,456,959

External References & Databases

Ensembl (ENSG00000176619)NCBI Gene (84823)OMIM (150341)HGNC:6638GenCCUniProt (Q03252)AlphaFoldClinVar (LMNB2)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~29.3 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

microcephaly 27, primary, autosomal dominantSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0030929

Submitter: G2P

lipodystrophy, partial, acquired, susceptibility toLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0100476

Submitter: Ambry Genetics

microcephaly 27, primary, autosomal dominantSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0030929

Submitter: PanelApp Australia

lipodystrophy, partial, acquired, susceptibility toLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0100476

Submitter: PanelApp Australia

microcephalyMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0001149

Submitter: Franklin by Genoox

Examining a cohort of patients with extreme microcephaly, from the Deciphering Developmental Disorders Study. Four microcephalic individuals from the DDD cohort and one individual from the 100kGP study with the same variant in LMNB2 (NM_032737.4: c.1192G>A, p.Glu398Lys). In most of the cases this variant was found to be de novo

progressive myoclonic epilepsy type 9SUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014685

Submitter: Orphanet

progressive myoclonic epilepsy type 9STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014685

Submitter: Labcorp Genetics (formerly Invitae)

lipodystrophy, partial, acquired, susceptibility toLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0100476

Submitter: Labcorp Genetics (formerly Invitae)

microcephaly 27, primary, autosomal dominantSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0030929

Submitter: Labcorp Genetics (formerly Invitae)

progressive myoclonic epilepsy type 9LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0014685

Submitter: Ambry Genetics

microcephaly 27, primary, autosomal dominantLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0030929

Submitter: Ambry Genetics

central nervous system malformationLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0020022

Submitter: Ambry Genetics

progressive myoclonic epilepsy type 9LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0014685

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Liopdystrophy, partial, acquired; Microcephaly 27, primary, autosomal dominant; Epilepsy, progressive myoclonic, 9AD/AR

Manifestation: Craniofacial; Musculoskeletal; Neurologic

Intervention: General

Rationale: 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

Refs: 16826530; 22768673; 25954030; 33033404Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LMNB2 variants in ClinVar

10 Conditions Cataloged
Lipodystrophy, partial, acquired, susceptibility toTotal: 574
Progressive myoclonic epilepsy type 9Total: 573
not specifiedTotal: 178
not providedTotal: 83
LMNB2-related disorderTotal: 21
Microcephaly 27, primary, autosomal dominantTotal: 13
Acquired partial lipodystrophyTotal: 3
Neurodevelopmental disorderTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032737.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
168
clinvar
4
clinvar
 173
missense
3
clinvar
296
clinvar
57
clinvar
8
clinvar
 364
nonsense
4
clinvar
 4
start loss
0
frameshift
1
clinvar
3
clinvar
 4
splice donor/acceptor (+/-2bp)
2
clinvar
 2
Total4030622512547
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 22 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_032737.4RefSeqNP_116126.312MANE Select
ENST00000325327.4EnsemblENSP00000327054.312MANE Select
ENST00000867388.1EnsemblENSP00000537447.112Standard
ENST00000867389.1EnsemblENSP00000537448.112Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • 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

Biological Process

  • biological_process

Molecular Function

  • molecular_function
  • structural molecule activity
  • protein binding

Cellular Component

  • nuclear inner membrane
  • lamin filament
  • nuclear membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000325327
Coding exons
12
Length
29359
Individuals with no LoFs
0
Homozygous LoFs
0
Heterozygous LoFs
0
Defined
0
p
0.00
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.6593593960.9070.00002993991
Missense (PolyPhen)113153.710.735161492
Synonymous-0.4741871791.050.00001441252
Loss of Function4.95028.50.000.00000142330

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)00.0absent
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec
0.243

Intolerance Scores

RVIS EVS
-1.13
RVIS percentile EVS
6.51

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Indispensability pred.
E
Indispensability score
0.804

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
Feedback | API | MCP | Annotate VCF | Sitemap | About | Privacy & Terms
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.