LBR

lamin B receptor, the group of Tudor domain containing

Basic information

Region (hg38): 1:225401502-225428925

Links

ENSG00000143815 ∙ NCBI:3930 ∙ OMIM:600024 ∙ HGNC:6518 ∙ Uniprot:Q14739 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Greenberg dysplasia (Definitive), mode of inheritance: AR
• Pelger-Huet anomaly (Moderate), mode of inheritance: AD
• Greenberg dysplasia (Moderate), mode of inheritance: AR
• Greenberg dysplasia (Supportive), mode of inheritance: AR
• regressive spondylometaphyseal dysplasia (Supportive), mode of inheritance: AR
• Greenberg dysplasia (Strong), mode of inheritance: AR
• regressive spondylometaphyseal dysplasia (Strong), mode of inheritance: AR
• Pelger-Huet anomaly (Strong), mode of inheritance: AD
• Greenberg dysplasia (Moderate), mode of inheritance: AR
• regressive spondylometaphyseal dysplasia (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Reynolds syndrome; Pelger-Huet anomaly; Rhizomelic skeletal dysplasia with or without Pelger-Huet anomaly; Greenberg dysplasia	AD/AR	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; Hematologic; Musculoskeletal	5553949; 3475111; 12118250; 14684694; 12618959; 20522425; 22338047

ClinVar

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

• not_provided (297 variants)
• Inborn_genetic_diseases (79 variants)
• Greenberg_dysplasia (79 variants)
• LBR-related_disorder (21 variants)
• Pelger-Hu�t_anomaly (21 variants)
• Regressive_spondylometaphyseal_dysplasia (15 variants)
• Connective_tissue_disorder (15 variants)
• Reynolds_syndrome (11 variants)
• not_specified (6 variants)
• RHIZOMELIC_SKELETAL_DYSPLASIA_WITH_PELGER-HUET_ANOMALY (6 variants)
• Anadysplasia-like,_spontaneously_remitting_spondylometaphyseal_dysplasia (2 variants)
• Jeune_thoracic_dystrophy (2 variants)
• RHIZOMELIC_SKELETAL_DYSPLASIA_WITHOUT_PELGER-HUET_ANOMALY (1 variants)
• Retrognathia (1 variants)
• Short_long_bone (1 variants)
• Rhizomelic_arm_shortening (1 variants)
• Disproportionate_short_stature (1 variants)
• Rhizomelic_leg_shortening (1 variants)
• Femoral_bowing (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LBR gene is commonly pathogenic or not. These statistics are base on transcript: NM_000002296.4. 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			2	61	1	64
missense	6	9	189	25	1	230
nonsense	3	2	1			6
start loss	1					1
frameshift	6	1				7
splice donor/acceptor (+/-2bp)	2	1	1			4
Total	18	13	193	86	2

Highest pathogenic variant AF is 0.00024414848

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LBR	protein_coding	protein_coding	ENST00000338179	13	27424

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.181	0.819	125732	0	16	125748	0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.289	337	352	0.957	0.0000206	4000
Missense in Polyphen		136	156.68	0.86803		1785
Synonymous	1.19	110	127	0.866	0.00000725	1189
Loss of Function	4.29	9	37.2	0.242	0.00000249	387

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.0000995	0.0000992
East Asian	0.000163	0.000163
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000791	0.0000791
Middle Eastern	0.000163	0.000163
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Anchors the lamina and the heterochromatin to the inner nuclear membrane. {ECO:0000269|PubMed:10828963}.
• Disease: DISEASE: Pelger-Huet anomaly (PHA) [MIM:169400]: An autosomal dominant inherited abnormality of granulocytes, characterized by abnormal ovoid shape, reduced nuclear segmentation and an apparently looser chromatin structure. {ECO:0000269|PubMed:14617022}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Greenberg dysplasia (GRBGD) [MIM:215140]: A rare autosomal recessive chondrodystrophy characterized by early in utero lethality. Affected fetuses typically present with fetal hydrops, short-limbed dwarfism, and a marked disorganization of chondro-osseous calcification, and ectopic ossification centers. {ECO:0000269|PubMed:12618959}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Reynolds syndrome (REYNS) [MIM:613471]: A syndrome specifically associating limited cutaneous systemic sclerosis and primary biliary cirrhosis. It is characterized by liver disease, telangiectasia, abrupt onset of digital paleness or cyanosis in response to cold exposure or stress (Raynaud phenomenon), and variable features of scleroderma. The liver disease is characterized by pruritis, jaundice, hepatomegaly, increased serum alkaline phosphatase and positive serum mitochondrial autoantibodies, all consistent with primary biliary cirrhosis. {ECO:0000269|PubMed:20522425}. Note=The disease may be caused by mutations affecting the gene represented in this entry.
• Pathway: Gastric Cancer Network 2;ATM Signaling Network in Development and Disease;Metabolism of lipids;zymosterol biosynthesis;Metabolism;cholesterol biosynthesis III (via desmosterol);cholesterol biosynthesis II (via 24,25-dihydrolanosterol);superpathway of cholesterol biosynthesis;Metabolism of steroids;cholesterol biosynthesis I;Cholesterol biosynthesis (Consensus)

Recessive Scores

• pRec: 0.291

Intolerance Scores

• loftool: 0.0224
• rvis_EVS: -0.71
• rvis_percentile_EVS: 14.71

Haploinsufficiency Scores

• pHI: 0.623
• hipred: Y
• hipred_score: 0.825
• ghis: 0.603

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.581

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Lbr
• Phenotype: immune system phenotype; renal/urinary system phenotype; skeleton phenotype; limbs/digits/tail 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); digestive/alimentary phenotype; vision/eye phenotype; reproductive system phenotype; 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; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype; craniofacial 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; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan)

Gene ontology

• Biological process: cholesterol biosynthetic process;sterol biosynthetic process;oxidation-reduction process
• Cellular component: nuclear envelope;nuclear inner membrane;integral component of nuclear inner membrane;membrane;integral component of membrane;nuclear membrane
• Molecular function: DNA binding;RNA binding;protein binding;lamin binding;delta14-sterol reductase activity;chromo shadow domain binding