IGKC

immunoglobulin kappa constant, the group of Immunoglobulin kappa locus at 2p11.2

Basic information

Region (hg38): 2:88857160-88857683

Links

ENSG00000211592 ∙ NCBI:3514 ∙ OMIM:147200 ∙ HGNC:5716 ∙ Uniprot:P01834 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• recurrent infections associated with rare immunoglobulin isotypes deficiency (Supportive), mode of inheritance: Unknown
• recurrent infections associated with rare immunoglobulin isotypes deficiency (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunoglobulin kappa light chain deficiency	AR	General	The clinical relevance of the condition is unclear	General	4117311; 812574; 815819; 3931219

ClinVar

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

• - (4 variants)
• Recurrent infections associated with rare immunoglobulin isotypes deficiency (2 variants)

Variants pathogenicity by type

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

Variants in IGKC

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

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

Position	Type	Phenotype	Significance	ClinVar
2-88857435-C-G		-	no classification for the single variant (-)
2-88857435-C-C		-	no classification for the single variant (-)
2-88857548-G-A		-	no classification for the single variant (-)
2-88857548-G-G		-	no classification for the single variant (-)
2-88857564-A-C		Recurrent infections associated with rare immunoglobulin isotypes deficiency	Pathogenic (Oct 25, 1985)
2-88857564-A-G		Recurrent infections associated with rare immunoglobulin isotypes deficiency	Pathogenic (Oct 25, 1985)

GnomAD

Source: gnomAD

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral immunity, the membrane-bound immunoglobulins serve as receptors which, upon binding of a specific antigen, trigger the clonal expansion and differentiation of B lymphocytes into immunoglobulins-secreting plasma cells. Secreted immunoglobulins mediate the effector phase of humoral immunity, which results in the elimination of bound antigens (PubMed:22158414, PubMed:20176268). The antigen binding site is formed by the variable domain of one heavy chain, together with that of its associated light chain. Thus, each immunoglobulin has two antigen binding sites with remarkable affinity for a particular antigen. The variable domains are assembled by a process called V-(D)-J rearrangement and can then be subjected to somatic hypermutations which, after exposure to antigen and selection, allow affinity maturation for a particular antigen (PubMed:17576170, PubMed:20176268). {ECO:0000303|PubMed:17576170, ECO:0000303|PubMed:20176268, ECO:0000303|PubMed:22158414}.
• Disease: DISEASE: Immunoglobulin kappa light chain deficiency (IGKCD) [MIM:614102]: A disease characterized by the complete absence of immunoglobulin kappa chains. {ECO:0000269|PubMed:3931219}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Antigen activates B Cell Receptor (BCR) leading to generation of second messengers;B cell receptor signaling;Signaling by the B Cell Receptor (BCR);FCGR activation;Role of phospholipids in phagocytosis;Fcgamma receptor (FCGR) dependent phagocytosis;FCERI mediated MAPK activation;FCERI mediated Ca+2 mobilization;Fc epsilon receptor (FCERI) signaling;Innate Immune System;Immune System;Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell;Adaptive Immune System;CD22 mediated BCR regulation;Initial triggering of complement;Classical antibody-mediated complement activation;Cell surface interactions at the vascular wall;Hemostasis;Regulation of actin dynamics for phagocytic cup formation;Regulation of Complement cascade;Creation of C4 and C2 activators;Complement cascade;FCERI mediated NF-kB activation;Role of LAT2/NTAL/LAB on calcium mobilization (Consensus)

Haploinsufficiency Scores

• ghis: 0.420

Essentials

• gene_indispensability_pred: E
• gene_indispensability_score: 0.539

Gene ontology

• Biological process: retina homeostasis;proteolysis;receptor-mediated endocytosis;phagocytosis, recognition;phagocytosis, engulfment;immune response;complement activation;complement activation, classical pathway;regulation of complement activation;Fc-epsilon receptor signaling pathway;Fc-gamma receptor signaling pathway involved in phagocytosis;defense response to bacterium;innate immune response;regulation of immune response;B cell receptor signaling pathway;positive regulation of B cell activation;leukocyte migration
• Cellular component: extracellular region;extracellular space;plasma membrane;external side of plasma membrane;immunoglobulin complex, circulating;extracellular exosome;blood microparticle
• Molecular function: antigen binding;serine-type endopeptidase activity;immunoglobulin receptor binding