LAMB2

laminin subunit beta 2, the group of Laminin subunits

Basic information

Region (hg38): 3:49121114-49133118

Previous symbols: [ "LAMS" ]

Links

ENSG00000172037 ∙ NCBI:3913 ∙ OMIM:150325 ∙ HGNC:6487 ∙ Uniprot:P55268 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Pierson syndrome (Strong), mode of inheritance: AR
• Pierson syndrome (Supportive), mode of inheritance: AR
• Pierson syndrome (Definitive), mode of inheritance: AR
• LAMB2-related infantile-onset nephrotic syndrome (Strong), mode of inheritance: AR
• LAMB2-related infantile-onset nephrotic syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pierson syndrome; Nephrotic syndrome, type 5, with or without ocular abnormalities	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	Musculoskeletal; Neurologic; Ophthalmologic; Renal	14136829; 15367484; 16912710; 17256789; 19251977; 21236492
Chronic renal dialysis can extend life of affected individuals

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LAMB2 gene.

• LAMB2-related infantile-onset nephrotic syndrome;Pierson syndrome (15 variants)
• Pierson syndrome;LAMB2-related infantile-onset nephrotic syndrome (15 variants)
• not provided (7 variants)
• Pierson syndrome (4 variants)
• LAMB2-related infantile-onset nephrotic syndrome (4 variants)
• LAMB2-related disorder (3 variants)
• Nephrotic syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LAMB2 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			13	179	2	194
missense		3	497	18	7	525
nonsense	12	5				17
start loss						0
frameshift	21	9	1			31
inframe indel			5			5
splice donor/acceptor (+/-2bp)	6	9				15
splice region			19	39		58
non coding			11	80	4	95
Total	39	26	527	277	13

Highest pathogenic variant AF is 0.0000328

Variants in LAMB2

This is a list of pathogenic ClinVar variants found in the LAMB2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-49121134-T-C		LAMB2-related infantile-onset nephrotic syndrome • Pierson syndrome • LAMB2-related infantile-onset nephrotic syndrome;Pierson syndrome	Uncertain significance (Dec 12, 2021)
3-49121228-AC-A			Uncertain significance (Jun 14, 2021)
3-49121233-C-A			Uncertain significance (Mar 06, 2023)
3-49121238-G-A		Pierson syndrome;LAMB2-related infantile-onset nephrotic syndrome	Likely benign (Mar 30, 2022)
3-49121244-G-C		LAMB2-related infantile-onset nephrotic syndrome;Pierson syndrome • Inborn genetic diseases • LAMB2-related infantile-onset nephrotic syndrome	Uncertain significance (Oct 24, 2022)
3-49121268-T-C		Pierson syndrome;LAMB2-related infantile-onset nephrotic syndrome	Likely benign (Sep 19, 2022)
3-49121273-G-A		LAMB2-related infantile-onset nephrotic syndrome • Pierson syndrome	Uncertain significance (Jan 13, 2018)
3-49121276-C-T		Inborn genetic diseases	Uncertain significance (Dec 20, 2023)
3-49121277-G-A		Pierson syndrome;LAMB2-related infantile-onset nephrotic syndrome	Likely benign (Jan 27, 2019)
3-49121286-C-G		Inborn genetic diseases	Uncertain significance (Mar 02, 2023)
3-49121291-C-G		LAMB2-related infantile-onset nephrotic syndrome	Uncertain significance (-)
3-49121294-C-T		LAMB2-related infantile-onset nephrotic syndrome;Pierson syndrome	Uncertain significance (Jul 21, 2020)
3-49121311-G-A		Inborn genetic diseases	Uncertain significance (May 20, 2024)
3-49121313-T-A		Pierson syndrome;LAMB2-related infantile-onset nephrotic syndrome	Likely benign (May 11, 2023)
3-49121320-C-T		Inborn genetic diseases	Uncertain significance (Dec 12, 2023)
3-49121322-C-T		LAMB2-related infantile-onset nephrotic syndrome;Pierson syndrome	Likely benign (Jun 08, 2022)
3-49121330-C-T		not specified • LAMB2-related infantile-onset nephrotic syndrome • Pierson syndrome • Pierson syndrome;LAMB2-related infantile-onset nephrotic syndrome • Focal segmental glomerulosclerosis	Benign/Likely benign (Feb 22, 2024)
3-49121337-A-G		LAMB2-related infantile-onset nephrotic syndrome • Pierson syndrome • LAMB2-related infantile-onset nephrotic syndrome;Pierson syndrome	Conflicting classifications of pathogenicity (Oct 27, 2023)
3-49121342-C-T		Inborn genetic diseases	Uncertain significance (Jun 02, 2023)
3-49121349-G-C		Pierson syndrome;LAMB2-related infantile-onset nephrotic syndrome	Likely benign (Aug 09, 2022)
3-49121369-A-G		Pierson syndrome;LAMB2-related infantile-onset nephrotic syndrome	Likely benign (Oct 07, 2021)
3-49121370-G-A		LAMB2-related infantile-onset nephrotic syndrome;Pierson syndrome	Likely benign (Oct 26, 2023)
3-49121389-G-C			Likely benign (Mar 02, 2020)
3-49121399-C-T			Likely benign (Apr 13, 2021)
3-49121420-C-T		Pierson syndrome;LAMB2-related infantile-onset nephrotic syndrome	Likely benign (Aug 08, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LAMB2	protein_coding	protein_coding	ENST00000418109	32	12005

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.50e-19	1.00	125607	0	141	125748	0.000561

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.775	994	1.07e+3	0.933	0.0000733	11606
Missense in Polyphen		359	435.66	0.82403		4865
Synonymous	0.628	385	401	0.960	0.0000226	3715
Loss of Function	4.29	46	89.9	0.512	0.00000562	946

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000792	0.000792
Ashkenazi Jewish	0.000398	0.000397
East Asian	0.000925	0.000925
Finnish	0.000236	0.000231
European (Non-Finnish)	0.000672	0.000668
Middle Eastern	0.000925	0.000925
South Asian	0.000490	0.000490
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.
• Disease: DISEASE: Pierson syndrome (PIERSS) [MIM:609049]: Characterized by nephrotic syndrome with neonatal onset, diffuse mesangial sclerosis and eye abnormalities with microcoria as the leading clinical feature. Death usually occurs within the first weeks of life. Disease severity depends on the mutation type: nontruncating LAMB2 mutations may display variable phenotypes ranging from a milder variant of Pierson syndrome to isolated congenital nephrotic syndrome. {ECO:0000269|PubMed:15367484, ECO:0000269|PubMed:16912710}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Nephrotic syndrome 5 with or without ocular abnormalities (NPHS5) [MIM:614199]: A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form and progress to end-stage renal failure. NPHS5 is characterized by very early onset of progressive renal failure. A subset of patients may develop mild ocular anomalies, such as myopia, nystagmus, and strabismus. {ECO:0000269|PubMed:20798252, ECO:0000269|PubMed:21236492}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);ECM-receptor interaction - Homo sapiens (human);Focal adhesion - Homo sapiens (human);Small cell lung cancer - Homo sapiens (human);Amoebiasis - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Alpha 6 Beta 4 signaling pathway;Primary Focal Segmental Glomerulosclerosis FSGS;miRNA targets in ECM and membrane receptors;Focal Adhesion;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Inflammatory Response Pathway;Signal Transduction;prion pathway;Post-translational protein phosphorylation;Alpha6Beta4Integrin;Laminin interactions;Post-translational protein modification;Metabolism of proteins;Extracellular matrix organization;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs);agrin in postsynaptic differentiation;a6b1 and a6b4 Integrin signaling;Non-integrin membrane-ECM interactions;ECM proteoglycans;MET activates PTK2 signaling;MET promotes cell motility;Signaling by MET;Signaling by Receptor Tyrosine Kinases;Beta1 integrin cell surface interactions;Alpha6 beta4 integrin-ligand interactions (Consensus)

Recessive Scores

• pRec: 0.419

Intolerance Scores

• loftool: 0.840
• rvis_EVS: -1.46
• rvis_percentile_EVS: 3.76

Haploinsufficiency Scores

• pHI: 0.172
• hipred: N
• hipred_score: 0.477
• ghis: 0.581

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.697

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Lamb2
• Phenotype: growth/size/body region phenotype; cellular phenotype; immune system phenotype; homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); vision/eye 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); renal/urinary system phenotype

Zebrafish Information Network

• Gene name: lamb2
• Affected structure: slow muscle cell
• Phenotype tag: abnormal
• Phenotype quality: retracted

Gene ontology

• Biological process: cell adhesion;axon guidance;neuromuscular junction development;visual perception;astrocyte development;Schwann cell development;extracellular matrix organization;post-translational protein modification;cellular protein metabolic process;axon extension involved in regeneration;retina development in camera-type eye;metanephric glomerular visceral epithelial cell development;metanephric glomerular basement membrane development
• Cellular component: extracellular region;basement membrane;laminin-3 complex;endoplasmic reticulum lumen;neuromuscular junction;synaptic cleft;laminin-11 complex;collagen-containing extracellular matrix;extracellular exosome
• Molecular function: integrin binding;structural molecule activity;extracellular matrix structural constituent