IGK

Summary

IGK (immunoglobulin kappa locus, HGNC:5715) is a protein-coding gene on chromosome 2p11.2.

At a glance

• Clinical variants (ClinVar): 16 total — 2 pathogenic

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5715
Approved symbol	IGK
Name	immunoglobulin kappa locus
Location	2p11.2
Locus type	gene with protein product
Status	Approved
Entrez	50802

Gene structure

Transcript identifiers

Ensembl transcripts: 0

RefSeq mRNA: 0 — MANE Select: None

Canonical transcript exons

None — 0 exons

Expression profiles

Top tissues by expression

0 total, by Bgee expression score (0-100, higher = more expressed):

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

Literature-anchored findings (GeneRIF, showing 20)

• The Ig molecule sequence of a single monoclonal IgG1 kappa cryoglobulin from a pt with chronic lymphocytic leukaemia & glomerulonephritis revealed alterations of charge & hydrophobicity promoting crystal-like aggregation & microtubule aggregation. (PMID:12100030)
• A Bence Jones V kappa l light chain monoclonal antibody fragment is reported that is responsible for myeloma-associated proximal tubulopathy with increased phosphaturia manifested as tubular acidosis and phosphate loss. (PMID:12552516)
• Matrix-scaffold attachment regions of this gene were identified on the basis of sequence conservation. (PMID:12615002)
• Study describes in detail three atypical recombination signal sequences that occur in the Ig kappa locus in B cell malignancies as well as in normal tonsillar B cells, showing how they fit in a scheme of sequential IGK rearrangements. (PMID:15356136)
• Isolated from multiple myeloma patients, this protein in crystal form may shed some light on the formation of fibrils common to certain storage diseases. (PMID:16508097)
• Inactivation of functional Ig kappa variable-junctional region joints by secondary rearrangements indicates active receptor editing in chronic lymphocytic leukemia (CLL) and provides evidence for the role of antigen in CLL immunopathogenesis. (PMID:16622520)
• Epigenetic mechanisms that initially bring about monoallelic variable-(diversity)-joining rearrangement continue to be involved in the control of antibody diversity at later stages of B cell development. (PMID:17546032)
• immunoglobulin variable kappa gene mutations may have a role in cutaneous B-cell lymphoma (PMID:17600686)
• the 5658-G allele and 3635-C allele were risk factors for both gastric cancer (odds ratio [OR]: 1.64 and 1.67, respectively) and breast cancer (OR: 1.94 and 1.56, respectively) (PMID:19072568)
• Patients with Crohn’s disease show greatly increased levels of circulating immunoglobulin lambda and kappa chains. (PMID:20505143)
• Cytogenetic analysis of high-grade lymphoma samples identified a MYC-IGK juxtaposition in seven patients and three translocation t(2;8)-positive cell lines. (PMID:22120970)
• EBV-encoded LMP1 upregulates Igkappa 3’enhancer activity and Igkappa expression in nasopharyngeal cancer cells by activating the Ets-1 through ERKs signaling (PMID:22396784)
• Data indicate that serum free light chain kappa/lambda ratio (rFLC) showed the highest sensitivity (91.8%) to differentiate multiple myeloma (MM) from non-MM. (PMID:22503879)
• Results indicate IGKV3 proteins as “off-the-shelf” vaccines for a large fraction of lymphoma patients. (PMID:22705988)
• Study indicates the role of the differential analysis of monomeric and dimeric kappa- and lambda-immunoglobulin (Ig) free light chains (FLC) for the precise diagnosis of multiple sclerosis (MS). (PMID:23376556)
• Newly obtained FabA17 antibody is a fully functional reactibody with reactivity comparable to that of the variant. (PMID:24598740)
• Data suggest that the possible subsets of B cells that might be depleted as a result of an immunotherapy targeting free immunoglobulin kappa light chain (FkappaLC), termed kappa myeloma antigen (KMA). (PMID:25149546)
• data suggest that mechanisms regulating the expression or not of IGK rearrangements may also contribute to repertoire development and also that this latter component of the selection process is defective in SLE. (PMID:25700344)
• These results suggest that myeloid cells-derived IgK may have a role in leukemogenesis and may serve as a novel tumor marker for monitoring minimal residual disease and developing target therapy. (PMID:26429876)
• Igh and Igk loci use different folding principles for V gene recombination due to distinct chromosomal architectures of pro-B and pre-B cells. (PMID:37085514)

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Canonical reviewed UniProt: None (reviewed: )

All UniProt accessions (0):

RefSeq proteins (0): (*=MANE)

Domains & families (InterPro)

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 0 (showing top):

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (0):

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

0 interactions, top by confidence:

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

16 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	0
Likely benign	2
Benign	12

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
29758	NC_000002.12:g.88857564A>G	Pathogenic
29759	NC_000002.12:g.88857564A>C	Pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

0 scored. Top likely-pathogenic:

Disease associations

OMIM: gene `` | disease phenotypes: MIM:614102

GenCC curated gene-disease

Mondo (1): recurrent infections associated with rare immunoglobulin isotypes deficiency (MONDO:0013576)

Orphanet (1): Recurrent infections associated with rare immunoglobulin isotypes deficiency (Orphanet:183675)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C564131	Kappa-Chain Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases expression, increases abundance	1
Air Pollutants, Occupational	decreases expression	1
Cadmium	affects binding	1
Nickel	decreases expression	1
Zinc	affects binding	1
Aflatoxin B1	decreases methylation	1
Particulate Matter	increases abundance, increases expression	1

Cellosaurus cell lines

6 cell lines: 6 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A630	JBL-2	Cancer cell line	Male
CVCL_C155	BL-64	Cancer cell line	Male
CVCL_M639	BL-21	Cancer cell line	Male
CVCL_N274	Ly66	Cancer cell line	Male
CVCL_N276	Ly91	Cancer cell line	Female
CVCL_W934	JI	Cancer cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.