Central nervous system non-hodgkin lymphoma

Summary

Central nervous system non-hodgkin lymphoma (MONDO:0044887) is a cancer with 4 cohort genes (7 GWAS associations across 1 studies; 2 CIViC-evidence somatic drivers) and 14 clinical trials. Top therapeutic interventions include belinostat, everolimus, and isotretinoin.

At a glance

• Classification: Cancer
• Cohort genes: 4
• GWAS associations: 7
• Clinical trials: 14

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	central nervous system non-hodgkin lymphoma
Mondo ID	MONDO:0044887
NCIT	C114779
SNOMED CT	448254007
UMLS	C2213246
MedGen	745669
GARD	0025918
Anatomy (UBERON)	UBERON:0001017
Is cancer (heuristic)	yes

Also known as: Central nervous system non-Hodgkin lymphoma · central nervous system non-Hodgkin lymphoma · non-Hodgkin lymphoma of central nervous system · Primary Central nervous system non-Hodgkin lymphoma

Data availability: 7 GWAS associations (1 study).

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › immune system cancer › primary central nervous system lymphoma › central nervous system non-hodgkin lymphoma

Related subtypes (2): spinal cord lymphoma, cerebral lymphoma

Subtypes (2): central nervous system anaplastic large cell lymphoma, diffuse large B-cell lymphoma of the central nervous system

Genetics & variants

GWAS landscape

7 GWAS associations across 1 studies. Top hits map to 3 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs116446171	2e-13	IRF4 - EXOC2	G	4.99
rs41289586	2e-08	ANO10	T	3.82
rs13254990	1e-07	PVT1	T	1.54
rs10806425	1e-07	BACH2	C	1.51
rs2395192	2e-07	HLA-DRB9 - HLA-DRB5	C	1.51
rs9271588	2e-06	HLA-DRB1 - HLA-DQA1	?	1.45
rs1964995	4e-06	HLA-DRB9 - HLA-DRB5	?	1.44

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST007896	Labreche K	2019	475	1,134	A genome-wide association study identifies susceptibility loci for primary central nervous system lymphoma at 6p25.3 and 3p22.1: a LOC network study.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	1
Tier 2: splice/UTR	0
Tier 3: regulatory	1
Tier 4: intronic/intergenic	5

MAF distribution

Bucket	Variants
common (>=0.05)	5
low_freq (0.01-0.05)	2
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	4
intergenic_variant	1
missense_variant	1
regulatory_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs116446171	6	484453	C>G	0.022	intergenic_variant	IRF4 - EXOC2	2e-13	Tier 4: intronic/intergenic
rs41289586	3	43577066	C>T	0.017	missense_variant	ANO10	2e-08	Tier 1: coding
rs13254990	8	128064205	C>T	0.33	intron_variant	PVT1	1e-07	Tier 4: intronic/intergenic
rs10806425	6	90216893	C>A	0.42	intron_variant	BACH2	1e-07	Tier 4: intronic/intergenic
rs2395192	6	32479867	C>A,G,T	0.41	intron_variant	HLA-DRB9 - HLA-DRB5	2e-07	Tier 4: intronic/intergenic
rs9271588	6	32623176	T>C	0.05	regulatory_region_variant	HLA-DRB1 - HLA-DQA1	2e-06	Tier 3: regulatory
rs1964995	6	32481634	T>A,C,G	0.05	intron_variant	HLA-DRB9 - HLA-DRB5	4e-06	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
BACH2			CIViC #14160
HLA-DRA			CIViC #2622

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BACH2	Orphanet:714472	Inflammatory bowel disease-autoimmunity-sinopulmonary infections-lymphadenopathy syndrome
ANO10	Orphanet:284289	Adult-onset autosomal recessive cerebellar ataxia
HLA-DRA	Orphanet:505	Graham Little-Piccardi-Lassueur syndrome

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BACH2	HGNC:14078	ENSG00000112182	Q9BYV9	Transcription regulator protein BACH2	gwas
EXOC2	HGNC:24968	ENSG00000112685	Q96KP1	Exocyst complex component 2	gwas
ANO10	HGNC:25519	ENSG00000160746	Q9NW15	Anoctamin-10	gwas
HLA-DRA	HGNC:4947	ENSG00000204287	P01903	HLA class II histocompatibility antigen, DR alpha chain	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BACH2	Transcription regulator protein BACH2	Transcriptional regulator that acts as a repressor or activator.
EXOC2	Exocyst complex component 2	Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane.
ANO10	Anoctamin-10	Does not exhibit calcium-activated chloride channel (CaCC) activity.
HLA-DRA	HLA class II histocompatibility antigen, DR alpha chain	An alpha chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule.

Protein-family classification

Druggable: 2 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.5

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Antibody/Immunoglobulin	2	14.6×	0.020
Transcription factor	1	2.1×	0.605
Other/Unknown	1	0.5×	0.962

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BACH2	Transcription factor	no		BTB/POZ_dom, bZIP_Maf, bZIP
EXOC2	Antibody/Immunoglobulin	yes		IPT_dom, Ig-like_fold, Ig_E-set
ANO10	Other/Unknown	no		Anoctamin, Anoctamin_TM
HLA-DRA	Antibody/Immunoglobulin	yes		MHC_II_a_N, Ig/MHC_CS, Ig_C1-set

Expression context

Cohort genes with no expression data: 0.

4 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	2
epithelium of nasopharynx	1
sural nerve	1
male germ line stem cell (sensu Vertebrata) in testis	1
middle temporal gyrus	1
duodenum	1
mucosa of transverse colon	1
stromal cell of endometrium	1
leukocyte	1
monocyte	1
vermiform appendix	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BACH2	237	ubiquitous	marker	cortical plate, sural nerve, epithelium of nasopharynx
EXOC2	255	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, middle temporal gyrus, cortical plate
ANO10	271	ubiquitous	marker	stromal cell of endometrium, mucosa of transverse colon, duodenum
HLA-DRA	132	broad	marker	monocyte, leukocyte, vermiform appendix

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HLA-DRA	3,244
EXOC2	2,587
BACH2	1,917
ANO10	766

Structural data

PDB: 3 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HLA-DRA	P01903	140
ANO10	Q9NW15	5
BACH2	Q9BYV9	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
EXOC2	Q96KP1	80.82

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 20. Enrichment computed across 4 evidence-associated genes (3 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Induction of Cell-Cell Fusion	1	292.8×	0.022	ANO10
Translocation of ZAP-70 to Immunological synapse	1	211.5×	0.022	HLA-DRA
Phosphorylation of CD3 and TCR zeta chains	1	181.3×	0.022	HLA-DRA
Co-inhibition by PD-1	1	173.0×	0.022	HLA-DRA
VxPx cargo-targeting to cilium	1	173.0×	0.022	EXOC2
Insulin processing	1	152.3×	0.022	EXOC2
Generation of second messenger molecules	1	115.3×	0.025	HLA-DRA
Late SARS-CoV-2 Infection Events	1	97.6×	0.026	ANO10
Translocation of SLC2A4 (GLUT4) to the plasma membrane	1	51.4×	0.040	EXOC2
Stimuli-sensing channels	1	45.3×	0.040	ANO10
Downstream TCR signaling	1	42.8×	0.040	HLA-DRA
Interferon gamma signaling	1	41.8×	0.040	HLA-DRA
Ion channel transport	1	32.0×	0.048	ANO10
MHC class II antigen presentation	1	29.7×	0.048	HLA-DRA
SARS-CoV-2 Infection	1	26.8×	0.049	ANO10
SARS-CoV Infections	1	18.5×	0.066	ANO10
Viral Infection Pathways	1	10.3×	0.111	ANO10
Transport of small molecules	1	8.4×	0.122	ANO10
Infectious disease	1	8.3×	0.122	ANO10
Disease	1	4.4×	0.212	ANO10

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
antigen processing and presentation of peptide or polysaccharide antigen via MHC class II	1	4213.0×	0.003	HLA-DRA
primary adaptive immune response involving T cells and B cells	1	4213.0×	0.003	BACH2
antigen processing and presentation of endogenous peptide antigen via MHC class II	1	2106.5×	0.004	HLA-DRA
myeloid dendritic cell antigen processing and presentation	1	1404.3×	0.004	HLA-DRA
regulation of T-helper cell differentiation	1	1053.2×	0.004	HLA-DRA
positive regulation of CD4-positive, alpha-beta T cell activation	1	1053.2×	0.004	HLA-DRA
positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation	1	842.6×	0.004	HLA-DRA
regulation of entry of bacterium into host cell	1	842.6×	0.004	EXOC2
import into nucleus	1	601.9×	0.005	BACH2
positive regulation of memory T cell differentiation	1	468.1×	0.006	HLA-DRA
obsolete vesicle tethering involved in exocytosis	1	468.1×	0.006	EXOC2
peptide antigen assembly with MHC class II protein complex	1	263.3×	0.009	HLA-DRA
obsolete vesicle docking involved in exocytosis	1	168.5×	0.013	EXOC2
Golgi to plasma membrane transport	1	140.4×	0.014	EXOC2
antigen processing and presentation of exogenous peptide antigen via MHC class II	1	135.9×	0.014	HLA-DRA
positive regulation of T cell mediated cytotoxicity	1	127.7×	0.014	HLA-DRA
positive regulation of immune response	1	120.4×	0.014	HLA-DRA
positive regulation of T cell activation	1	110.9×	0.014	HLA-DRA
membrane fission	1	102.8×	0.015	EXOC2
cognition	1	71.4×	0.020	HLA-DRA
mitotic cytokinesis	1	64.8×	0.021	EXOC2
chloride transmembrane transport	1	59.3×	0.022	ANO10
monoatomic ion transmembrane transport	1	52.0×	0.024	ANO10
exocytosis	1	38.0×	0.032	EXOC2
adaptive immune response	1	21.1×	0.054	HLA-DRA
immune response	1	11.8×	0.092	HLA-DRA
protein transport	1	11.0×	0.095	EXOC2
negative regulation of transcription by RNA polymerase II	1	4.4×	0.215	BACH2
regulation of transcription by RNA polymerase II	1	2.9×	0.302	BACH2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 4

Druggability breadth: 1 of 4 evidence-associated genes (25%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BACH2	0	0
EXOC2	0	0
ANO10	0	0
HLA-DRA	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
BACH2	3	Binding:3

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Drug repurposing candidates

0 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	HLA-DRA
D	Druggable family + AlphaFold only, no drug	1	EXOC2
E	Difficult family or no structure, no drug	2	BACH2, ANO10

Undrugged target profiles

4 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
BACH2	3	—
EXOC2	0	—
ANO10	0	—
HLA-DRA	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 14.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE1	10
PHASE2	2
PHASE1/PHASE2	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00918333	PHASE1/PHASE2	COMPLETED	Panobinostat and Everolimus in Treating Patients With Recurrent Multiple Myeloma, Non-Hodgkin Lymphoma, or Hodgkin Lymphoma
NCT01789255	PHASE2	COMPLETED	Vorinostat, Tacrolimus, and Methotrexate in Preventing GVHD After Stem Cell Transplant in Patients With Hematological Malignancies
NCT01973062	PHASE2	TERMINATED	Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab in Primary Central Nervous System Non-Hodgkin Lymphoma
NCT00003970	PHASE1	COMPLETED	Genetic Testing Plus Irinotecan in Treating Patients With Solid Tumors or Lymphoma
NCT00004241	PHASE1	COMPLETED	17-N-Allylamino-17-Demethoxygeldanamycin in Treating Patients With Advanced Epithelial Cancer, Malignant Lymphoma, or Sarcoma
NCT00025415	PHASE1	COMPLETED	Imatinib Mesylate in Treating Patients With Advanced Cancer and Liver Dysfunction
NCT00098891	PHASE1	COMPLETED	MS-275 and Isotretinoin in Treating Patients With Metastatic or Advanced Solid Tumors or Lymphomas
NCT00293345	PHASE1	COMPLETED	3-AP and Gemcitabine in Treating Patients With Advanced Solid Tumors or Lymphoma
NCT00348985	PHASE1	COMPLETED	PXD101 and Bortezomib in Treating Patients With Advanced Solid Tumors or Lymphomas
NCT00499811	PHASE1	COMPLETED	Vorinostat in Treating Patients With Metastatic or Unresectable Solid Tumors or Lymphoma and Liver Dysfunction
NCT01158274	PHASE1	COMPLETED	RO4929097 and Capecitabine in Treating Patients With Refractory Solid Tumors
NCT01231919	PHASE1	COMPLETED	MK2206 in Treating Younger Patients With Recurrent or Refractory Solid Tumors or Leukemia
NCT01588015	PHASE1	COMPLETED	Vaccine Therapy in Preventing Cytomegalovirus Infection in Patients With Hematological Malignancies Undergoing Donor Stem Cell Transplant
NCT01000753	Not specified	COMPLETED	Collecting and Storing Tissue Samples From Patients With Rare or Cutaneous Non-Hodgkin Lymphoma

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
BELINOSTAT	4	1
EVEROLIMUS	4	1
ISOTRETINOIN	4	1
PANOBINOSTAT	4	1
YTTRIUM Y 90 IBRITUMOMAB TIUXETAN	4	1
ENTINOSTAT	3	1
TANESPIMYCIN	3	1
TRIAPINE	3	1
CHEMBL344227	0	1
CHEMBL4786163	0	1