Pancreatic cancer, susceptibility to, 1

Summary

Pancreatic cancer, susceptibility to, 1 (MONDO:0011739) is a cancer with 2 cohort genes.

At a glance

• Classification: Cancer
• Cohort genes: 2
• ClinVar variants: 162

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	pancreatic cancer, susceptibility to, 1
Mondo ID	MONDO:0011739
OMIM	606856
UMLS	C1847351
MedGen	339739
GARD	0027805
Is cancer (heuristic)	yes

Also known as: familial pancreatic carcinoma caused by mutation in PALLD · PALLD familial pancreatic carcinoma · pancreatic cancer, susceptibility to, 1 · pancreatic cancer, susceptibility to, type 1

Data availability: 162 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 › pancreatic cancer, 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, 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, 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

162 retrieved; paginated sample, class counts are floors:

81 uncertain significance, 26 benign, 24 conflicting classifications of pathogenicity, 19 benign/likely benign, 12 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
136014	NM_001166108.2(PALLD):c.2393T>C (p.Met798Thr)	CBR4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
348044	NM_001166108.2(PALLD):c.2891A>C (p.Asp964Ala)	CBR4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
476380	NM_001166108.2(PALLD):c.3087T>A (p.Phe1029Leu)	CBR4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
902156	NM_001166108.2(PALLD):c.2867C>T (p.Thr956Ile)	CBR4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
128094	NM_001166108.2(PALLD):c.1040C>T (p.Thr347Met)	PALLD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
128095	NM_001166108.2(PALLD):c.1273A>T (p.Thr425Ser)	PALLD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
128096	NM_001166108.2(PALLD):c.1289G>A (p.Arg430Gln)	PALLD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
128097	NM_001166108.2(PALLD):c.1394G>A (p.Arg465His)	PALLD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
128101	NM_001166108.2(PALLD):c.2084T>G (p.Leu695Arg)	PALLD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
128111	NM_001166108.2(PALLD):c.539C>T (p.Thr180Ile)	PALLD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
128113	NM_001166108.2(PALLD):c.731A>G (p.Gln244Arg)	PALLD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
128115	NM_001166108.2(PALLD):c.909A>T (p.Arg303Ser)	PALLD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
136001	NM_001166108.2(PALLD):c.1965-12840C>G	PALLD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
136007	NM_001166108.2(PALLD):c.1965-12594T>G	PALLD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1763878	NM_001166108.2(PALLD):c.856A>G (p.Ser286Gly)	PALLD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1780590	NM_001166108.2(PALLD):c.1811A>G (p.Asn604Ser)	PALLD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2572	NM_001166108.2(PALLD):c.1965-12616C>T	PALLD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
348026	NM_001166108.2(PALLD):c.65A>G (p.Lys22Arg)	PALLD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
348028	NM_001166108.2(PALLD):c.365C>T (p.Pro122Leu)	PALLD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
348031	NM_001166108.2(PALLD):c.502C>G (p.Leu168Val)	PALLD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
901517	NM_001166108.2(PALLD):c.556G>A (p.Ala186Thr)	PALLD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
902929	NM_001166108.2(PALLD):c.222C>T (p.Ser74=)	PALLD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
902930	NM_001166108.2(PALLD):c.229G>C (p.Glu77Gln)	PALLD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
902976	NM_001166108.2(PALLD):c.1011C>A (p.Asp337Glu)	PALLD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1792012	NM_001166108.2(PALLD):c.2539C>G (p.Leu847Val)	CBR4	Uncertain significance	criteria provided, multiple submitters, no conflicts
348053	NM_001166108.2(PALLD):c.*908A>G	CBR4	Uncertain significance	criteria provided, single submitter
348061	NM_001166108.2(PALLD):c.*1757T>G	CBR4	Uncertain significance	criteria provided, single submitter
348064	NM_001166108.2(PALLD):c.*1792T>A	CBR4	Uncertain significance	criteria provided, single submitter
348070	NM_001166108.2(PALLD):c.*2070G>C	CBR4	Uncertain significance	criteria provided, single submitter
348075	NM_001166108.2(PALLD):c.*2166A>G	CBR4	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · Orphanet: 1 · 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
PALLD	Limited	Autosomal dominant	pancreatic cancer, susceptibility to, 1

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PALLD	Orphanet:1333	Familial pancreatic carcinoma

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PALLD	HGNC:17068	ENSG00000129116	Q8WX93	Palladin	gencc,clinvar
CBR4	HGNC:25891	ENSG00000145439	Q8N4T8	3-oxoacyl-[acyl-carrier-protein] reductase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PALLD	Palladin	Cytoskeletal protein required for organization of normal actin cytoskeleton.
CBR4	3-oxoacyl-[acyl-carrier-protein] reductase	Component of the heterotetramer complex KAR (3-ketoacyl-[acyl carrier protein] reductase or 3-ketoacyl-[ACP] reductase) that forms part of the mitochondrial fatty acid synthase (mtFAS).

Protein-family classification

Druggable: 1 · Difficult: 0 · 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	1	14.6×	0.135
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PALLD	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, Ig-like_dom
CBR4	Other/Unknown	no		SDR_fam, Sc_DH/Rdtase_CS, NAD(P)-bd_dom_sf

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
blood vessel layer	1
heart right ventricle	1
saphenous vein	1
calcaneal tendon	1
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PALLD	302	ubiquitous	marker	saphenous vein, heart right ventricle, blood vessel layer
CBR4	291	ubiquitous	marker	secondary oocyte, calcaneal tendon, oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CBR4	3,519
PALLD	2,362

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PALLD	Q8WX93	2
CBR4	Q8N4T8	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 2 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
Fatty acyl-CoA biosynthesis	1	439.2×	0.009	CBR4
Fatty acid metabolism	1	131.3×	0.015	CBR4
Metabolism of lipids	1	31.6×	0.042	CBR4
Metabolism	1	11.6×	0.086	CBR4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
fatty-acyl-CoA biosynthetic process	1	936.2×	0.004	CBR4
keratinocyte development	1	766.0×	0.004	PALLD
daunorubicin metabolic process	1	766.0×	0.004	CBR4
doxorubicin metabolic process	1	648.1×	0.004	CBR4
protein heterotetramerization	1	526.6×	0.004	CBR4
dendrite self-avoidance	1	526.6×	0.004	PALLD
epithelial cell morphogenesis	1	468.1×	0.004	PALLD
fatty acid biosynthetic process	1	175.5×	0.010	CBR4
protein homotetramerization	1	118.7×	0.013	CBR4
homophilic cell-cell adhesion	1	70.2×	0.019	PALLD
cytoskeleton organization	1	66.3×	0.019	PALLD
axon guidance	1	45.3×	0.026	PALLD
actin cytoskeleton organization	1	39.6×	0.027	PALLD
cell migration	1	30.8×	0.032	PALLD

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
PALLD	0	0
CBR4	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	PALLD
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	CBR4

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PALLD	0	—
CBR4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.