IGL

Summary

IGL (immunoglobulin lambda locus, HGNC:5853) is a protein-coding gene on chromosome 22q11.2.

Immunoglobulins recognize foreign antigens and initiate immune responses such as phagocytosis and the complement system. Each immunoglobulin molecule consists of two identical heavy chains and two identical light chains. There are two classes of light chains, kappa and lambda. This region represents the germline organization of the lambda light chain locus. The locus includes V (variable), J (joining), and C (constant) segments. During B cell development, a recombination event at the DNA level joins a single V segment with a J segment; the C segment is later joined by splicing at the RNA level. Recombination of many different V segments with several J segments provides a wide range of antigen recognition. Additional diversity is attained by junctional diversity, resulting from the random additional of nucleotides by terminal deoxynucleotidyltransferase, and by somatic hypermutation, which occurs during B cell maturation in the spleen and lymph nodes. Several V segments and three C segments are known to be incapable of encoding a protein and are considered pseudogenes. The locus also includes several non-immunoglobulin genes, many of which are pseudogenes or are predicted by automated computational analysis or homology to other species.

Source: NCBI Gene 3535 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 365 total — 2 likely-pathogenic
• Phenotypes (HPO): 2

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5853
Approved symbol	IGL
Name	immunoglobulin lambda locus
Location	22q11.2
Locus type	gene with protein product
Status	Approved
Entrez	3535

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

Literature-anchored findings (GeneRIF, showing 16)

• Nomenclature of the human immunoglobulin lambda (IGL) genes. (PMID:11872955)
• Imprint of somatic hypermutation differs in immunoglobulin heavy and lambda chain variable gene segments. (PMID:12749909)
• 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)
• Selection into the productive Vlambda repertoire in principal might be driven mainly by autoantigens in the newborn, as well as in adulthood, since newborns have not been exposed to exogenous antigens. (PMID:17675156)
• analysis of immunoglobulin light chain gene translocations in non-Hodgkin’s lymphoma as assessed by fluorescence in situ hybridisation (PMID:18005388)
• Results have shown that RNA interference can markedly reduce LC synthesis and provide the basis for testing the therapeutic potential of this strategy using in vivo experimental models of multiple myeloma. (PMID:20637260)
• We present a CD5-positive, CCND1-negative B-cell lymphoma with a novel translocation involving CCND2 and the immunoglobulin lambda (IGL) gene. (PMID:21504716)
• In survivors of chronic kidney failure, median serum levels of free kappa plus lambda immunoglobulin light chains are significantly higher compared with nonsurvivors. (PMID:21646814)
• 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)
• A humanized rat strain carries a chimeric human/rat IgH locus together with fully human IgL loci (variable kappas linked to Jkappa-Ckappa and Vlambdas linked to Jlambda-Clambda). (PMID:23303672)
• 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)
• The origin of deletion 22q11 in chronic lymphocytic leukemia is related to the rearrangement of immunoglobulin lambda light chain locus. (PMID:23608880)
• Mutation of lambda 6 light chain is associated with amyloidogenesis. (PMID:24107228)
• The active center of A17lambda antibody is displaced, stabilized and made more rigid owing to interdomain interactions involving the complementarity determining region(CDR)s from the variable light (VL) chain and variable heavy (VH) chain domains. (PMID:24598740)
• In eosinophilic oesophagitis, serum Ig-fLC appeared higher in female than male children. (PMID:24698291)
• the monomeric form of the Mcg immunoglobulin light chain variable domain as the quaternary unit required for amyloid fiber assembly. (PMID:25138218)

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	2
Uncertain significance	274
Likely benign	35
Benign	8

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
545270	NC_000022.11:g.(?21956007)(22224188_?)del	Likely pathogenic
545271	NC_000022.11:g.(?21959229)(22218520_?)del	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

0 scored. Top likely-pathogenic:

Disease associations

OMIM: gene `` | disease phenotypes: MIM:258040, MIM:181500, MIM:209850

GenCC curated gene-disease

Mondo (3): exstrophy-epispadias complex (MONDO:0017919), schizophrenia (MONDO:0005090), autism (MONDO:0005260)

Orphanet (3): Exstrophy-epispadias complex (Orphanet:322), Cloacal exstrophy (Orphanet:93929), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0100753	Schizophrenia
HP:0000717	Autism

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
terbufos	decreases methylation	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
CGP 52608	affects binding, increases reaction	1
Arsenic Trioxide	affects binding, decreases reaction	1
Cadmium	affects binding	1
Copper	affects binding	1
Fonofos	decreases methylation	1
Methotrexate	decreases expression	1
Nickel	affects binding	1
Parathion	decreases methylation	1
Zinc	affects binding	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	decreases expression	1

Cellosaurus cell lines

17 cell lines: 17 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1966	BL-2	Cancer cell line	Male
CVCL_1Q44	Maku	Cancer cell line	Male
CVCL_7034	BL-60	Cancer cell line	Female
CVCL_B3QN	ShK	Cancer cell line
CVCL_C147	BL-37	Cancer cell line	Male
CVCL_C166	BL-89	Cancer cell line	Male
CVCL_C539	PA682 PB	Cancer cell line	Male
CVCL_D4A7	BL-106	Cancer cell line
CVCL_IU39	YM	Cancer cell line	Male
CVCL_IU52	BL-84	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04760028	PHASE4	COMPLETED	Study on the Influencing Factors of Electroencephalogram Parameters Under Anesthesia
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients