B2M

beta-2-microglobulin, the group of C1-set domain containing

Basic information

Region (hg38): 15:44711358-44718851

Links

ENSG00000166710 ∙ NCBI:567 ∙ OMIM:109700 ∙ HGNC:914 ∙ Uniprot:P61769 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• MHC class I deficiency (Supportive), mode of inheritance: AR
• variant ABeta2M amyloidosis (Supportive), mode of inheritance: AD
• hypoproteinemia, hypercatabolic (Strong), mode of inheritance: AR
• familial visceral amyloidosis (Limited), mode of inheritance: AD
• hypoproteinemia, hypercatabolic (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Amyloidosis, hereditary systemic 6; Immunodeficiency 43	AD/AR	Allergy/Immunology/Infectious; Gastrointestinal	Individuals with Immunodeficiency can have susceptibility to infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Individuals with Hereditary amyloidosis may require liver transplantation	Allergy/Immunology/Infectious; Cardiovascular; Gastrointestinal; Neurologic; Renal	4186801; 2254461; 16549777; 22693999; 25702838

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the B2M gene.

• Non-Hodgkin lymphoma (1 variants)
• Familial visceral amyloidosis, Ostertag type (1 variants)
• Hypoproteinemia, hypercatabolic (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the B2M 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				14		14
missense	1		21			22
nonsense	1					1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region				1		1
non coding				8		8
Total	2	1	21	22	0

Variants in B2M

This is a list of pathogenic ClinVar variants found in the B2M region.

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

Position	Type	Phenotype	Significance	ClinVar
15-44711547-A-G		Multiple myeloma • Gastric adenocarcinoma • Ovarian serous cystadenocarcinoma • Lung adenocarcinoma • Non-Hodgkin lymphoma • Neoplasm of the large intestine • Squamous cell lung carcinoma • Squamous cell carcinoma of the head and neck • Malignant melanoma of skin • Small cell lung carcinoma • Neoplasm	Likely pathogenic (May 31, 2016)
15-44711547-A-T		Lung adenocarcinoma • Multiple myeloma • Neoplasm of the large intestine • Gastric adenocarcinoma • Small cell lung carcinoma • Non-Hodgkin lymphoma • Squamous cell lung carcinoma • Ovarian serous cystadenocarcinoma • Squamous cell carcinoma of the head and neck • Malignant melanoma of skin	Likely pathogenic (May 31, 2016)
15-44711548-T-A		Neoplasm	- (-)
15-44711548-T-C		Lung adenocarcinoma • Multiple myeloma • Squamous cell carcinoma of the head and neck • Small cell lung carcinoma • Non-Hodgkin lymphoma • Ovarian serous cystadenocarcinoma • Squamous cell lung carcinoma • Neoplasm of the large intestine • Malignant melanoma of skin • Gastric adenocarcinoma	Likely pathogenic (May 31, 2016)
15-44711548-T-G		Neoplasm of the large intestine • Non-Hodgkin lymphoma • Small cell lung carcinoma • Squamous cell lung carcinoma • Lung adenocarcinoma • Ovarian serous cystadenocarcinoma • Squamous cell carcinoma of the head and neck • Malignant melanoma of skin • Multiple myeloma • Gastric adenocarcinoma	Likely pathogenic (May 31, 2016)
15-44711549-G-A		Neoplasm of the large intestine • Non-Hodgkin lymphoma • Ovarian serous cystadenocarcinoma • Malignant melanoma of skin • Multiple myeloma • Lung adenocarcinoma • Squamous cell carcinoma of the head and neck • Gastric adenocarcinoma • Small cell lung carcinoma • Squamous cell lung carcinoma	Likely pathogenic (May 31, 2016)
15-44711551-C-T		Hypoproteinemia, hypercatabolic	Uncertain significance (Dec 27, 2017)
15-44711553-C-T		Hypoproteinemia, hypercatabolic	Uncertain significance (Aug 19, 2022)
15-44711554-G-A		Hypoproteinemia, hypercatabolic	Uncertain significance (Aug 08, 2022)
15-44711566-T-A		Hypoproteinemia, hypercatabolic	Pathogenic (Mar 09, 2023)
15-44711570-T-C		Hypoproteinemia, hypercatabolic	Likely benign (Mar 25, 2023)
15-44711572-T-C		Neoplasm	- (-)
15-44711573-G-A		Hypoproteinemia, hypercatabolic	Likely benign (Dec 16, 2023)
15-44711577-G-C		Hypoproteinemia, hypercatabolic	Uncertain significance (Sep 01, 2021)
15-44711579-G-C		Hypoproteinemia, hypercatabolic	Likely benign (Jan 13, 2024)
15-44711581-T-C		Neoplasm	- (-)
15-44711582-ACT-A		Neoplasm	- (-)
15-44711587-CTCTT-C		Neoplasm	- (-)
15-44711596-G-A		Hypoproteinemia, hypercatabolic	Uncertain significance (Jan 19, 2022)
15-44711598-C-G		Hypoproteinemia, hypercatabolic	Uncertain significance (Jun 28, 2022)
15-44711601-G-T		Neoplasm	- (-)
15-44711607-A-G		Hypoproteinemia, hypercatabolic	Uncertain significance (Sep 04, 2021)
15-44711614-G-T		Hypoproteinemia, hypercatabolic • Hypoproteinemia, hypercatabolic;Familial visceral amyloidosis, Ostertag type	Likely pathogenic (Nov 30, 2021)
15-44711625-C-T		Hypoproteinemia, hypercatabolic • Familial visceral amyloidosis, Ostertag type;Hypoproteinemia, hypercatabolic	Likely benign (Aug 23, 2022)
15-44711632-C-T		Hypoproteinemia, hypercatabolic • Familial visceral amyloidosis, Ostertag type;Hypoproteinemia, hypercatabolic	Benign/Likely benign (Jan 08, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
B2M	protein_coding	protein_coding	ENST00000558401	3	7401

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.562	0.427	125502	0	1	125503	0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.812	43	60.8	0.707	0.00000319	764
Missense in Polyphen		12	23.827	0.50362		282
Synonymous	0.419	21	23.6	0.890	0.00000115	233
Loss of Function	2.04	1	6.69	0.149	3.64e-7	81

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000879	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. Exogenously applied M.tuberculosis EsxA or EsxA-EsxB (or EsxA expressed in host) binds B2M and decreases its export to the cell surface (total protein levels do not change), probably leading to defects in class I antigen presentation (PubMed:25356553). {ECO:0000269|PubMed:25356553}.
• Disease: DISEASE: Immunodeficiency 43 (IMD43) [MIM:241600]: A disorder characterized by marked reduction in serum concentrations of immunoglobulins and albumin, and hypoproteinemia due to hypercatabolism. Patients may suffer from recurrent respiratory tract infections and severe skin disease. {ECO:0000269|PubMed:16549777}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Amyloidosis 8 (AMYL8) [MIM:105200]: A form of hereditary generalized amyloidosis. Clinical features include extensive visceral amyloid deposits, renal amyloidosis resulting in nephrotic syndrome, arterial hypertension, hepatosplenomegaly, cholestasis, petechial skin rash. There is no involvement of the nervous system. {ECO:0000269|PubMed:22693999}. Note=The disease is caused by mutations affecting the gene represented in this entry. Apart from the presence of causative mutations, beta-2- microglobulin may adopt the fibrillar configuration of amyloid when its serum levels are persistently high. High beta(2)- microglobulin serum levels result in amyloidosis in patients on long-term hemodialysis (PubMed:7918443). In contrast to patients with dialysis-related amyloidosis, patients with hereditary amyloidosis have normal circulating concentrations of beta2- microglobulin (PubMed:22693999). {ECO:0000269|PubMed:22693999, ECO:0000269|PubMed:7918443}.
• Pathway: Antigen processing and presentation - Homo sapiens (human);Neutrophil degranulation;Disease;DAP12 signaling;DAP12 interactions;ras-independent pathway in nk cell-mediated cytotoxicity;antigen processing and presentation;Cytokine Signaling in Immune system;Host Interactions of HIV factors;HIV Infection;Infectious disease;Innate Immune System;Immune System;Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell;Adaptive Immune System;Endosomal/Vacuolar pathway;Antigen processing-Cross presentation;Class I MHC mediated antigen processing & presentation;Nef mediated downregulation of MHC class I complex cell surface expression;Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters;The role of Nef in HIV-1 replication and disease pathogenesis;Interferon gamma signaling;Antigen Presentation: Folding, assembly and peptide loading of class I MHC;Downstream signaling in naïve CD8+ T cells;Interferon Signaling;TCR signaling in naïve CD8+ T cells;IL12-mediated signaling events (Consensus)

Recessive Scores

• pRec: 0.783

Intolerance Scores

• rvis_EVS: 0.1
• rvis_percentile_EVS: 60.96

Haploinsufficiency Scores

• pHI: 0.147
• hipred: Y
• hipred_score: 0.504
• ghis: 0.596

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.539

Mouse Genome Informatics

• Gene name: B2m
• 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; immune system phenotype; liver/biliary system phenotype; neoplasm; 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); 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; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: retina homeostasis;positive regulation of T cell mediated cytotoxicity;response to molecule of bacterial origin;antigen processing and presentation of peptide antigen via MHC class I;antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent;antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-independent;antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent;positive regulation of T cell cytokine production;iron ion transport;negative regulation of neuron projection development;antigen processing and presentation of endogenous peptide antigen via MHC class I;positive regulation of protein binding;T cell differentiation in thymus;regulation of iron ion transport;protein refolding;response to drug;neutrophil degranulation;cellular protein metabolic process;innate immune response;regulation of erythrocyte differentiation;response to cadmium ion;positive regulation of receptor-mediated endocytosis;regulation of defense response to virus by virus;regulation of immune response;iron ion homeostasis;interferon-gamma-mediated signaling pathway;cellular response to iron ion;cellular response to iron(III) ion;negative regulation of receptor binding;positive regulation of receptor binding;positive regulation of ferrous iron binding;positive regulation of transferrin receptor binding
• Cellular component: Golgi membrane;extracellular region;extracellular space;endoplasmic reticulum lumen;Golgi apparatus;cytosol;plasma membrane;focal adhesion;external side of plasma membrane;ER to Golgi transport vesicle membrane;membrane;phagocytic vesicle membrane;early endosome membrane;early endosome lumen;specific granule lumen;MHC class I protein complex;recycling endosome membrane;extracellular exosome;tertiary granule lumen;HFE-transferrin receptor complex
• Molecular function: protein binding;identical protein binding