Leukemia, acute lymphoblastic, susceptibility to, 3

Summary

Leukemia, acute lymphoblastic, susceptibility to, 3 (MONDO:0014241) is a cancer caused by PAX5 (GenCC Definitive), with 1 cohort gene (1 CIViC-evidence somatic driver; 18 ClinVar predisposition records).

At a glance

• Classification: Cancer
• Causal gene: PAX5 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 18

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	leukemia, acute lymphoblastic, susceptibility to, 3
Mondo ID	MONDO:0014241
OMIM	615545
UMLS	C3809874
MedGen	816204
GARD	0027857
Is cancer (heuristic)	yes

Also known as: ALL3 · leukemia, acute lymphoblastic, susceptibility to, 3 · leukemia, acute lymphoblastic, susceptibility to, type 3 · PAX5 precursor B-cell acute lymphoblastic leukaemia · PAX5 precursor B-cell acute lymphoblastic leukemia · PAX5-related leukemia predisposition · precursor B-cell acute lymphoblastic leukaemia caused by mutation in PAX5 · precursor B-cell acute lymphoblastic leukemia caused by mutation in PAX5 · susceptibility to acute lymphoblastic leukaemia 3

Data availability: 18 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neoplastic syndrome › leukemia, acute lymphoblastic, susceptibility to, 3

Related subtypes (116): mosaic variegated aneuploidy syndrome, tuberous sclerosis, hereditary breast ovarian cancer syndrome, hereditary multiple osteochondromas, nevoid basal cell carcinoma syndrome, leukemia, chronic lymphocytic, susceptibility to, 2, blue rubber bleb nevus, cherubism, Beckwith-Wiedemann syndrome, multiple self-healing squamous epithelioma, erythroleukemia, familial, susceptibility to, goiter, multinodular 1, with or without Sertoli-Leydig cell tumors, hyperparathyroidism 2 with jaw tumors, Kaposi sarcoma, susceptibility to, hereditary leiomyomatosis and renal cell cancer, susceptibility to uveal melanoma, melanoma and neural system tumor syndrome, nasopharyngeal carcinoma, susceptibility to, 2, WAGR syndrome, neuroblastoma, susceptibility to, 1, Rothmund-Thomson syndrome, mismatch repair cancer syndrome 1, Wiskott-Aldrich syndrome, N syndrome, hereditary thrombocytopenia and hematologic cancer predisposition syndrome, prostate cancer/brain cancer susceptibility, Brooke-Spiegler syndrome, pancreatic cancer, susceptibility to, 1, Carney-Stratakis syndrome, nasopharyngeal carcinoma, susceptibility to, 1, ovarian cancer, susceptibility to, 1, colorectal cancer, susceptibility to, 1, lung cancer susceptibility 1, leukemia, chronic lymphocytic, susceptibility to, 1, Kostmann syndrome, colorectal cancer, susceptibility to, 2, colorectal cancer, susceptibility to, 3, colorectal cancer, susceptibility to, 5, colorectal cancer, susceptibility to, 6, colorectal cancer, susceptibility to, 7, leukemia, chronic lymphocytic, susceptibility to, 3, leukemia, chronic lymphocytic, susceptibility to, 4, leukemia, chronic lymphocytic, susceptibility to, 5, lung cancer susceptibility 3, colorectal cancer, susceptibility to, 8, colorectal cancer, susceptibility to, 9, colorectal cancer, susceptibility to, 10, colorectal cancer, susceptibility to, 11, lung cancer susceptibility 4, neuroblastoma, susceptibility to, 3, neuroblastoma, susceptibility to, 4, neuroblastoma, susceptibility to, 5, neuroblastoma, susceptibility to, 6, leukemia, acute lymphocytic, susceptibility to, 1, leukemia, acute lymphocytic, susceptibility to, 2, lung cancer susceptibility 5, BAP1-related tumor predisposition syndrome, familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome, Maffucci syndrome, basal cell carcinoma, susceptibility to, 7, colorectal cancer, susceptibility to, 12, cholangiocarcinoma, susceptibility to, progeroid features-hepatocellular carcinoma predisposition syndrome, neuroblastoma, susceptibility to, 7, DDX41-related hematologic malignancy predisposition syndrome, nasopharyngeal carcinoma, susceptibility to, 3, familial isolated hyperparathyroidism, intestinal polyposis syndrome, dyskeratosis congenita, familial rhabdoid tumor, multiple endocrine neoplasia, hereditary pheochromocytoma-paraganglioma, PTEN hamartoma tumor syndrome, familial multiple fibrofolliculoma, hereditary retinoblastoma, familial atypical multiple mole melanoma syndrome, hereditary nonpolyposis colon cancer, Li-Fraumeni syndrome, Cobb syndrome, neurofibromatosis, susceptibility to familial cutaneous melanoma, pancreatic cancer, susceptibility to, 5, leukemia, acute myeloid, susceptibility to, diffuse gastric and lobular breast cancer syndrome with or without cleft lip and/or palate, glioma susceptibility, hemangioma, capillary infantile, susceptibility to, CDH1-related diffuse gastric and lobular breast cancer syndrome, NTHL1-deficiency tumor predisposition syndrome, SAMD9-related spectrum and myeloid neoplasm risk, neuroblastoma, susceptibility to, 2, BARD1-related cancer predisposition, BRCA1-related cancer predisposition, BRCA2-related cancer predisposition, ATM-related cancer predisposition, CHEK2-related cancer predisposition, PALB2-related cancer predisposition, RAD51C-related cancer predisposition, RAD51D-related cancer predisposition, Li-fraumeni-like syndrome, breast cancer, familial, susceptibility to, 1, breast cancer, familial, susceptibility to, 2, breast cancer, familial, susceptibility to, 3, colorectal cancer, susceptibility to, 4, colorectal cancer, susceptibility to, on chromosome 15, ovarian cancer, familial, susceptibility to, 1, ovarian cancer, familial, susceptibility to, 2, ovarian cancer, familial, susceptibility to, 3, inherited hematologic cancer-predisposing syndrome, mosaic neurofibromatosis/schwannomatosis, tumor predisposition syndrome 2, prostate cancer, hereditary, X-linked 3, follicular lymphoma, susceptibility to, GPR161-related medulloblastoma predisposition, SAMD9L-related spectrum and myeloid neoplasm risk, HAVCR2-related cancer predisposition, EGLN1-related erythrocytosis and pheochromocytoma/paraganglioma predisposition

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

18 retrieved; paginated sample, class counts are floors:

11 uncertain significance, 3 conflicting classifications of pathogenicity, 1 likely pathogenic, 1 pathogenic, 1 likely benign, 1 risk factor

ClinVar	Variant (HGVS)	Gene	Classification	Review
1210158	NM_016734.3(PAX5):c.661C>T (p.Arg221Trp)	PAX5	Pathogenic	no assertion criteria provided
1210157	NM_016734.3(PAX5):c.419G>A (p.Arg140Gln)	LOC105376032	Likely pathogenic	criteria provided, multiple submitters, no conflicts
88892	NM_016734.3(PAX5):c.547G>A (p.Gly183Ser)	LOC105376032	risk factor	no assertion criteria provided
2871692	NM_016734.3(PAX5):c.411-12A>T	LOC105376032	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1172745	NM_016734.3(PAX5):c.253G>A (p.Gly85Arg)	PAX5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
135001	NM_016734.3(PAX5):c.638C>T (p.Ser213Leu)	PAX5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2577905	NM_016734.3(PAX5):c.490G>T (p.Val164Leu)	LOC105376032	Uncertain significance	criteria provided, multiple submitters, no conflicts
1336590	NM_016734.3(PAX5):c.961C>T (p.Pro321Ser)	PAX5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1691541	NM_016734.3(PAX5):c.22C>T (p.Pro8Ser)	PAX5	Uncertain significance	criteria provided, multiple submitters, no conflicts
2073122	NM_016734.3(PAX5):c.914G>A (p.Arg305His)	PAX5	Uncertain significance	criteria provided, multiple submitters, no conflicts
2444880	NM_016734.3(PAX5):c.887C>T (p.Pro296Leu)	PAX5	Uncertain significance	criteria provided, single submitter
2785249	NM_016734.3(PAX5):c.101C>T (p.Pro34Leu)	PAX5	Uncertain significance	criteria provided, multiple submitters, no conflicts
3597313	NM_016734.3(PAX5):c.780+5G>A	PAX5	Uncertain significance	criteria provided, single submitter
4626978	NM_016734.3(PAX5):c.133G>T (p.Ala45Ser)	PAX5	Uncertain significance	criteria provided, multiple submitters, no conflicts
517139	NM_016734.3(PAX5):c.1013-1G>A	PAX5	Uncertain significance	criteria provided, multiple submitters, no conflicts
620603	NM_016734.3(PAX5):c.1169G>A (p.Arg390His)	PAX5	Uncertain significance	criteria provided, single submitter
620623	NM_016734.3(PAX5):c.701T>C (p.Leu234Pro)	PAX5	Uncertain significance	criteria provided, multiple submitters, no conflicts
802486	NM_016734.3(PAX5):c.1013-6A>G	PAX5	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
PAX5	Act	DLBCLNOS,PRAD	CIViC #4111

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
PAX5	Definitive	Autosomal dominant	leukemia, acute lymphoblastic, susceptibility to, 3	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PAX5	Orphanet:641372	B-lymphoblastic leukemia/lymphoma with t(7;9)(q11.2;p13.2)

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PAX5	HGNC:8619	ENSG00000196092	Q02548	Paired box protein Pax-5	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PAX5	Paired box protein Pax-5	Transcription factor that plays an essential role in commitment of lymphoid progenitors to the B-lymphocyte lineage.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PAX5	Transcription factor	no		Paired_dom, Homeodomain-like_sf, Pax2_C

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
buccal mucosa cell	1
epithelium of nasopharynx	1
lymph node	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PAX5	131	tissue_specific	marker	buccal mucosa cell, epithelium of nasopharynx, lymph node

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PAX5	2,752

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PAX5	Q02548	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
RUNX1 regulates transcription of genes involved in BCR signaling	1	1903.3×	5e-04	PAX5

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
lateral ventricle development	1	1296.3×	0.006	PAX5
sensory organ development	1	674.1×	0.006	PAX5
embryonic cranial skeleton morphogenesis	1	581.1×	0.006	PAX5
adult behavior	1	468.1×	0.006	PAX5
skeletal muscle cell differentiation	1	343.9×	0.007	PAX5
B cell differentiation	1	218.9×	0.008	PAX5
cerebral cortex development	1	205.5×	0.008	PAX5
transcription by RNA polymerase II	1	70.5×	0.021	PAX5
nervous system development	1	45.9×	0.029	PAX5
spermatogenesis	1	35.2×	0.034	PAX5
negative regulation of transcription by RNA polymerase II	1	17.7×	0.062	PAX5
regulation of transcription by RNA polymerase II	1	11.7×	0.086	PAX5

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PAX5	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	PAX5

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PAX5	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.