Neuroblastoma, susceptibility to, 1

Summary

Neuroblastoma, susceptibility to, 1 (MONDO:0009741) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 97

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	neuroblastoma, susceptibility to, 1
Mondo ID	MONDO:0009741
OMIM	256700
UMLS	C2749485
MedGen	412713
GARD	0027791
Is cancer (heuristic)	no

Also known as: neuroblastoma, susceptibility to · neuroblastoma, susceptibility to, 1, autosomal dominant, somatic mutation · susceptibility to neuroblastoma

Data availability: 97 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neoplastic syndrome › neuroblastoma, susceptibility to, 1

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, 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, leukemia, acute lymphoblastic, susceptibility to, 3, 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

97 retrieved; paginated sample, class counts are floors:

70 uncertain significance, 22 conflicting classifications of pathogenicity, 3 benign/likely benign, 1 benign, 1 risk factor

ClinVar	Variant (HGVS)	Gene	Classification	Review
4659	NM_001365951.3(KIF1B):c.2075A>T (p.Glu692Val)	KIF1B	risk factor	no assertion criteria provided
1007653	NM_001365951.3(KIF1B):c.4970C>T (p.Ala1657Val)	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1284949	NM_001365951.3(KIF1B):c.2115+6581G>A	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1331070	NM_001365951.3(KIF1B):c.2115+7081C>T	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1419477	NM_001365951.3(KIF1B):c.4445G>A (p.Arg1482Gln)	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
155749	NM_001365951.3(KIF1B):c.3407T>C (p.Ile1136Thr)	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
155750	NM_001365951.3(KIF1B):c.4211T>C (p.Val1404Ala)	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
157531	NM_001365951.3(KIF1B):c.899A>G (p.Lys300Arg)	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1744917	NM_001365951.3(KIF1B):c.5173G>A (p.Val1725Ile)	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2712316	NM_001365951.3(KIF1B):c.184-6T>G	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291552	NM_001365951.3(KIF1B):c.1955C>T (p.Thr652Ile)	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3533871	NM_001365951.3(KIF1B):c.4056G>A (p.Arg1352=)	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3891480	NM_001365951.3(KIF1B):c.2115+6523G>A	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4660	NM_001365951.3(KIF1B):c.2618C>T (p.Thr873Ile)	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4661	NM_001365951.3(KIF1B):c.3787C>T (p.Pro1263Ser)	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
476776	NM_001365951.3(KIF1B):c.1364C>T (p.Thr455Met)	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
476778	NM_001365951.3(KIF1B):c.1594C>G (p.Pro532Ala)	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
476788	NM_001365951.3(KIF1B):c.5214C>G (p.Asp1738Glu)	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
570523	NM_001365951.3(KIF1B):c.2675+3A>G	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
843328	NM_001365951.3(KIF1B):c.1770C>G (p.Ser590Arg)	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
875167	NM_001365951.3(KIF1B):c.4282G>A (p.Gly1428Ser)	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
943303	NM_001365951.3(KIF1B):c.392A>G (p.Asn131Ser)	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
946995	NM_001365951.3(KIF1B):c.4297C>A (p.Pro1433Thr)	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1032652	NM_001365951.3(KIF1B):c.3434G>A (p.Arg1145His)	KIF1B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1039307	NM_001365951.3(KIF1B):c.668T>C (p.Ile223Thr)	KIF1B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1379326	NM_001365951.3(KIF1B):c.3827C>T (p.Ala1276Val)	KIF1B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1386186	NM_001365951.3(KIF1B):c.4543C>T (p.Arg1515Cys)	KIF1B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1389324	NM_001365951.3(KIF1B):c.3151A>G (p.Met1051Val)	KIF1B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1400116	NM_001365951.3(KIF1B):c.2824G>A (p.Asp942Asn)	KIF1B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1404980	NM_001365951.3(KIF1B):c.4195G>A (p.Val1399Ile)	KIF1B	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

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
KIF1B	Limited	Autosomal dominant	neuroblastoma, susceptibility to, 1	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KIF1B	Orphanet:29072	Hereditary pheochromocytoma-paraganglioma
KIF1B	Orphanet:99946	Autosomal dominant Charcot-Marie-Tooth disease type 2A1

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
KIF1B	HGNC:16636	ENSG00000054523	O60333	Kinesin-like protein KIF1B	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KIF1B	Kinesin-like protein KIF1B	Has a plus-end-directed microtubule motor activity and functions as a motor for transport of vesicles and organelles along microtubules.

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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KIF1B	Scaffold/PPI	no		FHA_dom, Kinesin_motor_dom, PH_domain

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
biceps brachii	1
medial globus pallidus	1
skeletal muscle tissue of rectus abdominis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KIF1B	287	ubiquitous	marker	skeletal muscle tissue of rectus abdominis, biceps brachii, medial globus pallidus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KIF1B	2,257

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KIF1B	O60333	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. 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
Kinesins	1	178.4×	0.019	KIF1B
Golgi-to-ER retrograde transport	1	132.8×	0.019	KIF1B
COPI-dependent Golgi-to-ER retrograde traffic	1	110.9×	0.019	KIF1B
Intra-Golgi and retrograde Golgi-to-ER traffic	1	104.8×	0.019	KIF1B
Factors involved in megakaryocyte development and platelet production	1	66.4×	0.024	KIF1B
Membrane Trafficking	1	37.1×	0.029	KIF1B
Hemostasis	1	36.0×	0.029	KIF1B
Vesicle-mediated transport	1	34.8×	0.029	KIF1B

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
retrograde neuronal dense core vesicle transport	1	3370.4×	0.001	KIF1B
neuron-neuron synaptic transmission	1	1685.2×	0.001	KIF1B
apoptotic process involved in development	1	1685.2×	0.001	KIF1B
mitochondrion transport along microtubule	1	1404.3×	0.001	KIF1B
anterograde synaptic vesicle transport	1	991.3×	0.002	KIF1B
neuromuscular synaptic transmission	1	601.9×	0.002	KIF1B
vesicle-mediated transport	1	96.3×	0.012	KIF1B
apoptotic process	1	28.7×	0.035	KIF1B

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KIF1B	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
KIF1B	1	Binding:1

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).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

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	KIF1B

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)
KIF1B	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.