PNLIP

pancreatic lipase, the group of Lipases

Basic information

Region (hg38): 10:116545930-116567855

Links

ENSG00000175535 ∙ NCBI:5406 ∙ OMIM:246600 ∙ HGNC:9155 ∙ Uniprot:P16233 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pancreatic triacylglycerol lipase deficiency (Limited), mode of inheritance: AR
• pancreatic triacylglycerol lipase deficiency (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pancreatic lipase deficiency	AR	Gastrointestinal	Individuals have been described with exocrine pancreatic failure, and medical management (eg, with ADEK vitamin and pancreatic enzyme replacement) has been described as beneficial	Gastrointestinal	24262094

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PNLIP gene.

• not provided (125 variants)
• Inborn genetic diseases (14 variants)
• Pancreatic triacylglycerol lipase deficiency (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PNLIP gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				26	11	37
missense			63	2	2	67
nonsense	1		4			5
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)		1	1			2
splice region			5	4		9
non coding				11	2	13
Total	1	1	69	39	15

Highest pathogenic variant AF is 0.00000657

Variants in PNLIP

This is a list of pathogenic ClinVar variants found in the PNLIP region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
10-116546096-C-T			Likely benign (Jun 03, 2023)
10-116546100-C-T			Uncertain significance (Jun 23, 2023)
10-116546104-T-G			Likely benign (Jan 09, 2023)
10-116546122-G-A			Likely benign (Oct 05, 2023)
10-116546130-C-T			Uncertain significance (May 06, 2022)
10-116546157-G-A			Likely benign (Aug 19, 2023)
10-116547278-T-G			Likely benign (Nov 12, 2023)
10-116547281-T-C			Likely benign (Feb 27, 2022)
10-116547286-G-C			Likely benign (Apr 27, 2023)
10-116547306-G-T			Uncertain significance (Oct 30, 2022)
10-116547310-C-T			Likely benign (Jul 23, 2022)
10-116547311-G-A			Uncertain significance (Nov 01, 2022)
10-116547317-C-T		not specified	Uncertain significance (Feb 17, 2024)
10-116547343-A-C			Benign (Jan 29, 2024)
10-116547346-G-A			Uncertain significance (Sep 06, 2022)
10-116547358-G-A			Likely benign (Aug 17, 2023)
10-116547362-A-G			Uncertain significance (May 07, 2022)
10-116547363-G-A			Uncertain significance (Jan 16, 2023)
10-116547371-C-T			Uncertain significance (Mar 23, 2023)
10-116547376-A-G			Uncertain significance (May 26, 2022)
10-116547378-T-G		not specified	Uncertain significance (Jun 30, 2023)
10-116547394-AG-A			Uncertain significance (Feb 23, 2023)
10-116547397-T-C			Likely benign (Sep 05, 2023)
10-116547407-C-G			Uncertain significance (Dec 28, 2022)
10-116547408-G-A		not specified	Uncertain significance (Dec 16, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PNLIP	protein_coding	protein_coding	ENST00000369221	12	21925

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.60e-8	0.845	125703	0	42	125745	0.000167

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.443	237	257	0.922	0.0000133	3050
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000326	0.000326
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.000185	0.000139
European (Non-Finnish)	0.000197	0.000193
Middle Eastern	0.0000544	0.0000544
South Asian	0.000134	0.000131
Other	0.000327	0.000326

dbNSFP

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.
• Pathway: 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;Signal Transduction;Metabolism of fat-soluble vitamins;Metabolism;Metabolism of vitamins and cofactors;Glycerophospholipid metabolism;retinol biosynthesis;triacylglycerol degradation;Retinoid metabolism and transport;G alpha (i) signalling events;Visual phototransduction;Digestion of dietary lipid;Digestion;Digestion and absorption;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.201

Intolerance Scores

• loftool: 0.256
• rvis_EVS: -0.69
• rvis_percentile_EVS: 15.12

Haploinsufficiency Scores

• pHI: 0.114
• hipred: N
• hipred_score: 0.350
• ghis: 0.429

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.804

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pnlip
• Phenotype: liver/biliary system phenotype; digestive/alimentary phenotype; homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype

Gene ontology

• Biological process: lipid metabolic process;lipid catabolic process;intestinal cholesterol absorption;positive regulation of triglyceride lipase activity
• Cellular component: extracellular region;extracellular space
• Molecular function: triglyceride lipase activity;lipase activity;metal ion binding