Pancreatic agenesis 2

Summary

Pancreatic agenesis 2 (MONDO:0014406) is a disease caused by PTF1A (GenCC Definitive), with 3 cohort genes.

At a glance

• Causal gene: PTF1A (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 15

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	pancreatic agenesis 2
Mondo ID	MONDO:0014406
OMIM	615935
DOID	DOID:0060988
UMLS	C4014737
MedGen	863174
GARD	0016033
Is cancer (heuristic)	no

Also known as: PAGEN2 · pancreatic agenesis 2 · pancreatic agenesis caused by mutation in PTF1A · pancreatic agenesis type 2 · PTF1A pancreatic agenesis

Data availability: 15 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › pancreatic agenesis › pancreatic agenesis 2

Related subtypes (3): pancreas, dorsal, agenesis of, pancreatic agenesis 1, pancreatic agenesis 3

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

15 retrieved; paginated sample, class counts are floors:

7 uncertain significance, 3 conflicting classifications of pathogenicity, 2 pathogenic/likely pathogenic, 1 pathogenic, 1 benign/likely benign, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
2429343	NM_001371909.1(C10orf67):c.1570+4090T>C	C10orf67	Pathogenic	criteria provided, single submitter
977150	NM_001368882.1(COL13A1):c.513del (p.Gly172fs)	COL13A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
800794	NM_178161.3(PTF1A):c.571C>A (p.Pro191Thr)	PTF1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
130054	NM_178161.3(PTF1A):c.269G>C (p.Gly90Ala)	PTF1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
130055	NM_178161.3(PTF1A):c.787T>C (p.Ser263Pro)	PTF1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
451673	NM_178161.3(PTF1A):c.44C>T (p.Ala15Val)	PTF1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1803846	NM_178161.3(PTF1A):c.987A>G (p.Ter329Trp)	PTF1A	Uncertain significance	criteria provided, single submitter
2179361	NM_178161.3(PTF1A):c.703_720del (p.Gly235_Gly240del)	PTF1A	Uncertain significance	criteria provided, multiple submitters, no conflicts
2502253	NM_178161.3(PTF1A):c.673T>G (p.Leu225Val)	PTF1A	Uncertain significance	criteria provided, single submitter
299625	NM_178161.3(PTF1A):c.617G>T (p.Arg206Leu)	PTF1A	Uncertain significance	criteria provided, multiple submitters, no conflicts
4279826	NM_178161.3(PTF1A):c.878A>C (p.Asn293Thr)	PTF1A	Uncertain significance	criteria provided, single submitter
877719	NM_178161.3(PTF1A):c.362G>A (p.Cys121Tyr)	PTF1A	Uncertain significance	criteria provided, multiple submitters, no conflicts
880486	NM_178161.3(PTF1A):c.8C>T (p.Ala3Val)	PTF1A	Uncertain significance	criteria provided, multiple submitters, no conflicts
299624	NM_178161.3(PTF1A):c.386C>T (p.Ala129Val)	PTF1A	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
299628	NM_178161.3(PTF1A):c.*15G>A	PTF1A	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · Orphanet: 4 · 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
PTF1A	Definitive	Autosomal recessive	permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome	12

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PTF1A	Orphanet:2805	Partial pancreatic agenesis
PTF1A	Orphanet:65288	Permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome
COL13A1	Orphanet:98913	Postsynaptic congenital myasthenic syndrome
COL13A1	Orphanet:98914	Presynaptic congenital myasthenic syndromes

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PTF1A	HGNC:23734	ENSG00000168267	Q7RTS3	Pancreas transcription factor 1 subunit alpha	gencc,clinvar
COL13A1	HGNC:2190	ENSG00000197467	Q5TAT6	Collagen alpha-1(XIII) chain	clinvar
C10orf67	HGNC:28716	ENSG00000179133	Q8IYJ2	Uncharacterized protein C10orf67, mitochondrial	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PTF1A	Pancreas transcription factor 1 subunit alpha	Transcription factor implicated in the cell fate determination in various organs.
COL13A1	Collagen alpha-1(XIII) chain	Involved in cell-matrix and cell-cell adhesion interactions that are required for normal development.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 2 · 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	2.8×	0.587
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PTF1A	Transcription factor	no		bHLH_dom, HLH_DNA-bd_sf, E-box_TF_Regulators
COL13A1	Other/Unknown	no		Collagen, Collagen_Structural_Proteins
C10orf67	Other/Unknown	no		DUF4709, DUF4724, C10orf67-like

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
body of pancreas	1
islet of Langerhans	1
pancreas	1
cerebellar cortex	1
cerebellar hemisphere	1
cerebellum	1
buccal mucosa cell	1
right uterine tube	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PTF1A	96	tissue_specific	marker	body of pancreas, pancreas, islet of Langerhans
COL13A1	209	ubiquitous	marker	cerebellar hemisphere, cerebellar cortex, cerebellum
C10orf67	137	tissue_specific	marker	buccal mucosa cell, tendon of biceps brachii, right uterine tube

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL13A1	1,308
PTF1A	1,213
C10orf67	177

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
C10orf67	Q8IYJ2	71.37
PTF1A	Q7RTS3	61.81
COL13A1	Q5TAT6	55.67

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. Enrichment computed across 3 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Regulation of gene expression in early pancreatic precursor cells	1	713.8×	0.008	PTF1A
Developmental Lineage of Pancreatic Acinar Cells	1	150.3×	0.014	PTF1A
Collagen chain trimerization	1	129.8×	0.014	COL13A1
Collagen degradation	1	87.8×	0.014	COL13A1
Collagen biosynthesis and modifying enzymes	1	85.2×	0.014	COL13A1
Integrin cell surface interactions	1	67.2×	0.015	COL13A1

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
regulation of neural retina development	1	2808.7×	0.005	PTF1A
morphogenesis of a branching structure	1	1053.2×	0.005	COL13A1
tissue development	1	936.2×	0.005	PTF1A
exocrine pancreas development	1	842.6×	0.005	PTF1A
amacrine cell differentiation	1	766.0×	0.005	PTF1A
neuron fate commitment	1	401.2×	0.006	PTF1A
pancreas development	1	337.0×	0.006	PTF1A
developmental process	1	337.0×	0.006	PTF1A
retina layer formation	1	324.1×	0.006	PTF1A
retinoic acid receptor signaling pathway	1	324.1×	0.006	PTF1A
endochondral ossification	1	271.8×	0.006	COL13A1
cerebellum development	1	179.3×	0.008	PTF1A
cell-matrix adhesion	1	81.8×	0.017	COL13A1
cell-cell adhesion	1	50.8×	0.025	COL13A1
transcription by RNA polymerase II	1	35.3×	0.034	PTF1A
regulation of DNA-templated transcription	1	15.8×	0.070	PTF1A
cell differentiation	1	14.6×	0.072	COL13A1
regulation of transcription by RNA polymerase II	1	5.8×	0.164	PTF1A

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 3 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
PTF1A	0	0
COL13A1	0	0
C10orf67	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	3	PTF1A, COL13A1, C10orf67

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PTF1A	0	—
COL13A1	0	—
C10orf67	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.