PNLIP

protein-coding

pancreatic lipase, the group of Lipases

Gene summary

This gene encodes a member of the lipase family of proteins. The encoded enzyme is secreted by the pancreas and hydrolyzes triglycerides in the small intestine, and is essential for the efficient digestion of dietary fats. Inhibition of the encoded enzyme may prevent high-fat diet-induced obesity in mice and result in weight loss in human patients with obesity. Mutations in this gene cause congenital pancreatic lipase deficiency, a rare disorder characterized by steatorrhea. [provided by RefSeq, Jul 2016]

MANE transcript

NM_000936.4

Inheritance

ClinVar variants

P:20U:120B:69

Top phenotype

Pancreatic lipase deficiency

gnomAD constraint

pLI —, LoF o/e 0.65

Max pathogenic AF

—

Genomic locus

chr10:116,545,931-116,567,855

External References & Databases

Ensembl (ENSG00000175535)

Transcript & Mutation Effects

hg38 • Region Span ~21.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

pancreatic triacylglycerol lipase deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013700

Submitter: Labcorp Genetics (formerly Invitae)

pancreatic triacylglycerol lipase deficiencyMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0013700

Submitter: PanelApp Australia

pancreatic triacylglycerol lipase deficiencyLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0013700

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Pancreatic lipase deficiencyAR

Manifestation: Gastrointestinal

Intervention: Gastrointestinal

Rationale: Individuals have been described with exocrine pancreatic failure, and medical management (eg, with ADEK vitamin and pancreatic enzyme replacement) has been described as beneficial

Refs: 24262094

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PNLIP variants in ClinVar

4 Conditions Cataloged

not providedTotal: 241

not specifiedTotal: 53

PNLIP-related disorderTotal: 9

Pancreatic triacylglycerol lipase deficiencyTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000936.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	57 clinvar	8 clinvar	67
missense	1 clinvar	1 clinvar	116 clinvar	2 clinvar	2 clinvar	122
nonsense	8 clinvar		1 clinvar			9
start loss						0
frameshift	5 clinvar					5
splice donor/acceptor (+/-2bp)		5 clinvar	1 clinvar			6
Total	14	6	120	59	10	209

Highest pathogenic variant AF is 0.00004342308

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000936.4	RefSeq	NP_000927.1	12	MANE Select
ENST00000369221.2	Ensembl	ENSP00000358223.2	12	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Glycerolipid metabolism - Homo sapiens (human)
Fat digestion and absorption - Homo sapiens (human)
Vitamin digestion and absorption - Homo sapiens (human)
Pancreatic secretion - Homo sapiens (human)
Signaling by GPCR

Biological Process

lipid metabolic process
lipid catabolic process
intestinal cholesterol absorption
positive regulation of triglyceride lipase activity

Molecular Function

triglyceride lipase activity
lipase activity
metal ion binding

Cellular Component

extracellular region
extracellular space

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000369221
Coding exons: 12
Length: 21925
Individuals with no LoFs: 125703
Homozygous LoFs: 0
Heterozygous LoFs: 42
Defined: 125745
p: 0.000167

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.443	237	257	0.922	0.0000133	3050
Missense (PolyPhen)		87	93.93	0.92622		1153
Synonymous	-0.792	104	94.2	1.10	0.00000527	881
Loss of Function	1.60	16	24.6	0.651	0.00000127	294

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00020	0.00020	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.000054	0.000054	rare
Finnish	0.00019	0.00014	rare
European (Non-Finnish)	0.00020	0.00019	rare
South Asian	0.00013	0.00013	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Disease: DISEASE: Pancreatic lipase deficiency (PNLIPD) [MIM:614338]: An autosomal recessive disorder characterized by exocrine pancreatic failure. Clinical findings include oily/greasy stools from infancy or early childhood, absence of discernible pancreatic disease, and significantly decreased pancreatic lipolytic activity. {ECO:0000269|PubMed:24262094, ECO:0000269|PubMed:25862608}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.201

Intolerance Scores

LoFtool: 0.256
RVIS EVS: -0.69
RVIS percentile EVS: 15.12

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.804

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium