IGKC
otherimmunoglobulin kappa constant, the group of Immunoglobulin kappa locus at 2p11.2
Gene summary
Predicted to enable antigen binding activity. Involved in adaptive immune response. Located in blood microparticle; extracellular exosome; and obsolete extracellular space. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~0.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: Unknown
Disease ID:MONDO:0013576
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0013576
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0013576
Submitter: ClinGen
IGKC was first reported in relation to autosomal recessive, recurrent infections associated with rare immunoglobulin isotypes deficiency (MONDO:0013576) in 1976 (Zegers BJ et al. PMID:815819). Authors identified compound heterozygosity for two point mutations in the IGKC gene, resulting in loss of an invariant tryptophan in one allele and an invariant cysteine in the other allele. Both mutations were predicted to abolish formation of stable intradomain disulfide bonds. Deficiencies in immunoglobulin isotypes are primary-immunodeficiencies that are often asymptomatic but can be characterized by recurrent sinopulmonary infections. There are three alleles, Km1, Km1 and 2, and Km3, that segregate at the Km locus in IGKC. The Km1 allele, without Km2, is extremely rare. Greater than 98% of the individuals positive for Km1 are also positive for Km2 (Moraru M et al. 2015, PMID:26179905). Some reported cases of K-chain deficiency present with increased susceptibility to pyogenic infections, while others reveal association with autoimmune diseases. Researchers hypothesize that selective K-chain deficiency may be a common genetic defect, however, only a few cases of have been reported due to the presentation of normal immune response to a variety of antigens and A chains ability to substitute efficiently (Pricop et al. 1995, PMID:7554465). At least 4 unique missense variants have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data. Variants in this gene have been reported in at least 6 probands in 5 publications (PMID: 815819, PMID: 4117311, PMID: 32278584, PMID: 26853951, PMID: 4132042). In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the ClinGen Antibody Immunodeficiencies GCEP on May 18th, 2021 (SOP Version 8).
Clinical Genomic Database (CGD)
Manifestation: General
Intervention: General
Rationale: The clinical relevance of the condition is unclear
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to IGKC variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript . 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.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 2 | 2 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 2 | 0 | 0 | 0 | 0 | 2 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| Ensembl | ENSP00000374777.2 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- 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
Biological Process
- retina homeostasis
- proteolysis
- receptor-mediated endocytosis
- phagocytosis, recognition
- phagocytosis, engulfment
Molecular Function
- antigen binding
- serine-type endopeptidase activity
- immunoglobulin receptor binding
Cellular Component
- extracellular region
- extracellular space
- plasma membrane
- external side of plasma membrane
- immunoglobulin complex, circulating
dbNSFP Gene Annotations
Source:
- 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.;
Essentials
- Indispensability pred.
- E
- Indispensability score
- 0.539