Pancreatic triacylglycerol lipase deficiency

Summary

Pancreatic triacylglycerol lipase deficiency (MONDO:0013700) is a disease caused by PNLIP (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Causal gene: PNLIP (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 4
• Phenotypes (HPO): 21

Clinical features

Signs & symptoms

Clinical features (HPO)

21 HPO clinical features (Orphanet curated; top 21 by frequency):

HPO ID	Term	Frequency
HP:0001738	Exocrine pancreatic insufficiency	Frequent (30-79%)
HP:0001824	Weight loss	Frequent (30-79%)
HP:0002027	Abdominal pain	Frequent (30-79%)
HP:0002570	Steatorrhea	Frequent (30-79%)
HP:0003270	Abdominal distention	Frequent (30-79%)
HP:0004905	Low levels of vitamin A	Frequent (30-79%)
HP:0011892	Low levels of vitamin K	Frequent (30-79%)
HP:0012378	Fatigue	Frequent (30-79%)
HP:0100512	Low levels of vitamin D	Frequent (30-79%)
HP:0100513	Low levels of vitamin E	Frequent (30-79%)
HP:0000939	Osteoporosis	Occasional (5-29%)
HP:0001097	Keratoconjunctivitis sicca	Occasional (5-29%)
HP:0001510	Growth delay	Occasional (5-29%)
HP:0001891	Iron deficiency anemia	Occasional (5-29%)
HP:0002014	Diarrhea	Occasional (5-29%)
HP:0002748	Rickets	Occasional (5-29%)
HP:0002749	Osteomalacia	Occasional (5-29%)
HP:0012047	Hemeralopia	Occasional (5-29%)
HP:0000707	Abnormality of the nervous system	Very rare (<1-4%)
HP:0000969	Edema	Very rare (<1-4%)
HP:0002583	Colitis	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	pancreatic triacylglycerol lipase deficiency
Mondo ID	MONDO:0013700
OMIM	614338
Orphanet	309031
ICD-11	349070670
NCIT	C129030
SNOMED CT	78960005
UMLS	C3280527
MedGen	482157
GARD	0017401
Is cancer (heuristic)	no

Also known as: pancreatic lipase deficiency · pancreatic triglyceride lipase deficiency · PNLIPD

Data availability: 4 ClinVar variants · 3 GenCC gene-disease records · 4 cell lines.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › digestive system disorder › pancreas disorder › pancreatic triacylglycerol lipase deficiency

Related subtypes (13): pancreatic steatorrhea, pancreatic mucinous ductal ectasia, exocrine pancreatic insufficiency, endocrine pancreas disorder, pancreatitis, annular pancreas, follicular cholangitis and pancreatitis, congenital pancreatic cyst, recurrent acute pancreatitis, accessory pancreas, pancreatic neoplasm, acinar cystic transformation of the pancreas, lymphoepithelial cyst of the pancreas

Subtypes (2): pancreatic colipase deficiency, combined pancreatic lipase-colipase deficiency

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

4 retrieved; paginated sample, class counts are floors:

2 pathogenic, 1 benign, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
427570	NM_000936.4(PNLIP):c.662C>T (p.Thr221Met)	PNLIP	Pathogenic	no assertion criteria provided
522506	NM_000936.4(PNLIP):c.1257G>A (p.Trp419Ter)	PNLIP	Pathogenic	criteria provided, single submitter
2435103	NM_000936.4(PNLIP):c.686A>G (p.Asn229Ser)	PNLIP	Uncertain significance	criteria provided, single submitter
1327426	NM_000936.4(PNLIP):c.486T>C (p.Asn162=)	PNLIP	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 0 · 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
PNLIP	Strong	Autosomal recessive	pancreatic triacylglycerol lipase deficiency	3

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
PNLIP	HGNC:9155	ENSG00000175535	P16233	Pancreatic triacylglycerol lipase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PNLIP	Pancreatic triacylglycerol lipase	Plays an important role in fat metabolism.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PNLIP	Enzyme (other)	yes	3.1.1.3	TAG_lipase, PLAT/LH2_dom, Lipase_panc

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
body of pancreas	1
islet of Langerhans	1
pancreas	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PNLIP	149	tissue_specific	marker	body of pancreas, pancreas, islet of Langerhans

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PNLIP	1,185

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PNLIP	P16233	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 12. 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
Digestion of dietary lipid	1	1631.4×	0.007	PNLIP
Digestion and absorption	1	761.3×	0.007	PNLIP
Digestion	1	571.0×	0.007	PNLIP
Metabolism of fat-soluble vitamins	1	380.7×	0.007	PNLIP
Developmental Lineage of Pancreatic Acinar Cells	1	300.5×	0.007	PNLIP
Visual phototransduction	1	259.6×	0.007	PNLIP
Retinoid metabolism and transport	1	248.3×	0.007	PNLIP
Developmental Cell Lineages	1	223.9×	0.007	PNLIP
Metabolism of vitamins and cofactors	1	116.5×	0.011	PNLIP
Sensory Perception	1	95.2×	0.013	PNLIP
Developmental Biology	1	14.5×	0.075	PNLIP
Metabolism	1	11.6×	0.086	PNLIP

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
positive regulation of triglyceride lipase activity	1	16852.0×	4e-04	PNLIP
intestinal cholesterol absorption	1	1404.3×	0.002	PNLIP
triglyceride catabolic process	1	802.5×	0.002	PNLIP
high-density lipoprotein particle remodeling	1	802.5×	0.002	PNLIP
fatty acid biosynthetic process	1	351.1×	0.004	PNLIP
cholesterol homeostasis	1	156.0×	0.007	PNLIP
lipid metabolic process	1	91.6×	0.011	PNLIP

Therapeutics

Drug target analysis

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

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

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
PNLIP	ORLISTAT

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PNLIP	3	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ORLISTAT	4	PNLIP
QUERCETIN	3	PNLIP
RAFOXANIDE	2	PNLIP

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
PNLIP	65	Binding:65

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PNLIP	3.1.1.3	triacylglycerol lipase

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

3 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.

Compound	Max phase	Cohort target (bioactivity)
ORLISTAT	4	PNLIP
QUERCETIN	3	PNLIP
RAFOXANIDE	2	PNLIP

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PNLIP
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.