LIPF

Summary

LIPF (lipase F, gastric type, HGNC:6622) is a protein-coding gene on chromosome 10q23.31, encoding Gastric triacylglycerol lipase (P07098). Catalyzes the hydrolysis of triacylglycerols to yield free fatty acids, diacylglycerol, monoacylglycerol, and glycerol.

This gene encodes gastric lipase, an enzyme involved in the digestion of dietary triglycerides in the gastrointestinal tract, and responsible for 30% of fat digestion processes occurring in human. It is secreted by gastric chief cells in the fundic mucosa of the stomach, and it hydrolyzes the ester bonds of triglycerides under acidic pH conditions. The gene is a member of a conserved gene family of lipases that play distinct roles in neutral lipid metabolism. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 8513 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 52 total
• Druggable target: yes
• MANE Select transcript: NM_004190

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6622
Approved symbol	LIPF
Name	lipase F, gastric type
Location	10q23.31
Locus type	gene with protein product
Status	Approved
Aliases	HGL, HLAL
Ensembl gene	ENSG00000182333
Ensembl biotype	protein_coding
OMIM	601980
Entrez	8513

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 2 retained_intron

ENST00000238983, ENST00000355843, ENST00000394375, ENST00000496797, ENST00000608620, ENST00000609378

RefSeq mRNA: 4 — MANE Select: NM_004190 NM_001198828, NM_001198829, NM_001198830, NM_004190

CCDS: CCDS55718, CCDS55719, CCDS65896, CCDS7389

Canonical transcript exons

ENST00000238983 — 10 exons

Exon	Start	End
ENSE00000810580	88667569	88667686
ENSE00000810581	88668558	88668756
ENSE00000810583	88671829	88671965
ENSE00000932776	88669837	88669946
ENSE00000932779	88673588	88673734
ENSE00002464829	88675586	88675657
ENSE00003652896	88676209	88676280
ENSE00003705884	88667287	88667402
ENSE00003899134	88664442	88664491
ENSE00003902644	88678445	88678814

Expression profiles

Bgee: expression breadth ubiquitous, 156 present calls, max score 99.99.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 5.2474 / max 9417.3862, expressed in 11 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
106057	5.2474	11

Top tissues by expression

285 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cardia of stomach	UBERON:0001162	99.99	gold quality
pylorus	UBERON:0001166	98.99	gold quality
body of stomach	UBERON:0001161	95.04	gold quality
stomach	UBERON:0000945	94.42	gold quality
right uterine tube	UBERON:0001302	93.05	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.34	gold quality
fundus of stomach	UBERON:0001160	88.92	gold quality
lower esophagus mucosa	UBERON:0035834	82.13	gold quality
mucosa of stomach	UBERON:0001199	81.92	gold quality
sperm	CL:0000019	80.37	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.89	gold quality
right coronary artery	UBERON:0001625	78.98	gold quality
male germ cell	CL:0000015	77.85	gold quality
endocervix	UBERON:0000458	76.39	gold quality
ectocervix	UBERON:0012249	75.84	gold quality
left uterine tube	UBERON:0001303	74.42	gold quality
right lung	UBERON:0002167	73.89	gold quality
body of pancreas	UBERON:0001150	73.39	gold quality
metanephros cortex	UBERON:0010533	70.99	gold quality
duodenum	UBERON:0002114	70.67	gold quality
right adrenal gland	UBERON:0001233	68.32	gold quality
mucosa of transverse colon	UBERON:0004991	68.12	gold quality
right ovary	UBERON:0002118	67.97	gold quality
right lobe of liver	UBERON:0001114	67.07	gold quality
pituitary gland	UBERON:0000007	66.72	gold quality
left adrenal gland	UBERON:0001234	66.58	gold quality
esophagus mucosa	UBERON:0002469	66.31	gold quality
transverse colon	UBERON:0001157	65.97	gold quality
spleen	UBERON:0002106	64.98	gold quality
left ovary	UBERON:0002119	64.92	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

9 targeting LIPF, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-548L	99.06	70.90	2560
HSA-MIR-4712-3P	98.52	65.39	822
HSA-MIR-192-3P	97.52	67.66	1001

Literature-anchored findings (GeneRIF, showing 8)

• Mechanisms of inhibition of triacylglycerol hydrolysis (PMID:11940604)
• identidfied the cap and the lid residues involved in the binding with the lipidic substrate (PMID:12941646)
• down-regulated KLF4, CHGA, GPX3, SST and LIPF, together with up-regulated SERPINH1, THY1 and INHBA is an 8-gene signature for gastric cancer (PMID:20043075)
• insights into the domain movements (PMID:20965171)
• Recombinant human gastric lipase (hGL) was transiently expressed in Nicotiana benthamiana leaves using the CPMV-HT expression system. (PMID:21945702)
• In patients with intrahepatic cholestasis of pregnancy, there was no elevation in LIPF mRNA in maternal circulation compared with controls. (PMID:25059952)
• LIPFDGKA might serve as a potential possible biomarkers for diagnosis of gastric cancer, and their downregulation may bring new perspective into the investigation of gastric cancer prognosis (PMID:27498782)
• site-directed mutagenesis the role of three key residues (K4, E225, R229) involved in salt bridges stabilizing the lid domain that controls the access to the active site and is part of the interfacial recognition site. Their substitution has an impact on the pH-dependent activity of rHGL and its relative activities on medium and long chain triglycerides. (PMID:28694218)

Cross-species orthologs

30 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lipf	ENSMUSG00000024768
rattus_norvegicus	Lipf	ENSRNOG00000019448
drosophila_melanogaster	Lip3	FBGN0023495
drosophila_melanogaster	Lip1	FBGN0023496
drosophila_melanogaster	Lip2	FBGN0024740
drosophila_melanogaster	CG2772	FBGN0031533
drosophila_melanogaster	Lip4	FBGN0032264
drosophila_melanogaster	CG18301	FBGN0032265
drosophila_melanogaster	CG18302	FBGN0032266
drosophila_melanogaster	CG7329	FBGN0032271
drosophila_melanogaster	CG3635	FBGN0032981
drosophila_melanogaster	CG8093	FBGN0033999
drosophila_melanogaster	CG11406	FBGN0034990
drosophila_melanogaster	mag	FBGN0036996
drosophila_melanogaster	CG11598	FBGN0038067
drosophila_melanogaster	CG11600	FBGN0038068
drosophila_melanogaster	CG11608	FBGN0038069
drosophila_melanogaster	CG6753	FBGN0038070
drosophila_melanogaster	CG18530	FBGN0042207
drosophila_melanogaster	CG18284	FBGN0043825
drosophila_melanogaster	CG31089	FBGN0051089
drosophila_melanogaster	CG31091	FBGN0051091
drosophila_melanogaster	CG31871	FBGN0051871
drosophila_melanogaster	CG31872	FBGN0051872
drosophila_melanogaster	CG17097	FBGN0265264
caenorhabditis_elegans		WBGENE00009773
caenorhabditis_elegans		WBGENE00010062
caenorhabditis_elegans		WBGENE00020016
caenorhabditis_elegans		WBGENE00021963
caenorhabditis_elegans		WBGENE00022642

Paralogs (5): LIPA (ENSG00000107798), LIPM (ENSG00000173239), LIPN (ENSG00000204020), LIPK (ENSG00000204021), LIPJ (ENSG00000204022)

Protein

Protein identifiers

Gastric triacylglycerol lipase — P07098 (reviewed: P07098)

All UniProt accessions (1): P07098

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the hydrolysis of triacylglycerols to yield free fatty acids, diacylglycerol, monoacylglycerol, and glycerol. Shows a preferential hydrolysis at the sn-3 position of triacylglycerol.

Subcellular location. Secreted.

Similarity. Belongs to the AB hydrolase superfamily. Lipase family.

Isoforms (4)

UniProt ID	Names	Canonical?
P07098-1	1	yes
P07098-2	2
P07098-3	3
P07098-4	4

RefSeq proteins (4): NP_001185757, NP_001185758, NP_001185759, NP_004181* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000073	AB_hydrolase_1	Domain
IPR025483	Lipase_euk	Family
IPR029058	AB_hydrolase_fold	Homologous_superfamily

Pfam: PF00561

Catalyzed reactions (Rhea), 3 shown:

• a triacylglycerol + H2O = a diacylglycerol + a fatty acid + H(+) (RHEA:12044)
• 1,2,3-tri-(9Z-octadecenoyl)-glycerol + H2O = 1,2-di-(9Z-octadecenoyl)-sn-glycerol + (9Z)-octadecenoate + H(+) (RHEA:39931)
• 1,2,3-trioctanoylglycerol + H2O = 1,2-dioctanoyl-sn-glycerol + octanoate + H(+) (RHEA:40047)

UniProt features (54 total): helix 23, strand 12, glycosylation site 4, sequence variant 3, active site 3, splice variant 2, turn 2, signal peptide 1, chain 1, disulfide bond 1, sequence conflict 1, domain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1HLG	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P07098-F1	90.13	0.76

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 172 (nucleophile); 343 (charge relay system); 372 (charge relay system)

Disulfide bonds (1): 246–255

Glycosylation sites (4): 34, 99, 271, 327

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-192456	Digestion of dietary lipid
R-HSA-8935690	Digestion
R-HSA-8963743	Digestion and absorption

MSigDB gene sets: 64 (showing top): GOBP_DICARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_NEUTRAL_LIPID_METABOLIC_PROCESS, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_CH_OH_GROUP_OF_DONORS, VECCHI_GASTRIC_CANCER_EARLY_DN, GOBP_LIPID_CATABOLIC_PROCESS, BECKER_TAMOXIFEN_RESISTANCE_DN, KEGG_GLYCEROLIPID_METABOLISM, GOMF_TRIACYLGLYCEROL_LIPASE_ACTIVITY, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS, GOMF_CARBOXYLIC_ESTER_HYDROLASE_ACTIVITY, GOMF_LIPASE_ACTIVITY, GOMF_LIPID_BINDING

GO Biological Process (4): malate metabolic process (GO:0006108), lipid metabolic process (GO:0006629), triglyceride metabolic process (GO:0006641), lipid catabolic process (GO:0016042)

GO Molecular Function (8): triacylglycerol lipase activity (GO:0004806), lipid binding (GO:0008289), malate dehydrogenase activity (GO:0016615), protein binding (GO:0005515), lipase activity (GO:0016298), hydrolase activity (GO:0016787), hydrolase activity, acting on ester bonds (GO:0016788), carboxylic ester hydrolase activity (GO:0052689)

GO Cellular Component (2): extracellular region (GO:0005576), mitochondrion (GO:0005739)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Digestion	1
Digestion and absorption	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
hydrolase activity, acting on ester bonds	2
dicarboxylic acid metabolic process	1
primary metabolic process	1
acylglycerol metabolic process	1
lipid metabolic process	1
catabolic process	1
lipase activity	1
carboxylic ester hydrolase activity	1
oxidoreductase activity, acting on CH-OH group of donors	1
catalytic activity	1
hydrolase activity	1
cellular anatomical structure	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1392 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LIPF	PNLIP	P16233	982
LIPF	CLPS	P04118	944
LIPF	PNLIPRP1	P54315	920
LIPF	LIPC	P11150	809
LIPF	LPL	P06858	727
LIPF	PGA4	P00790	696
LIPF	CEL	P19835	619
LIPF	SCGB1D2	O95969	548
LIPF	GKN1	Q9NS71	517
LIPF	PGA4	P00790	484
LIPF	LIPG	Q9Y5X9	477
LIPF	PGA4	P00790	456
LIPF	ANKRD22	Q5VYY1	439
LIPF	PNLIPRP3	Q17RR3	434
LIPF	GKN2	Q86XP6	424

IntAct

6 interactions, top by confidence:

A	B	Type	Score
LIPF	LRSAM1	psi-mi:“MI:0915”(physical association)	0.500
LIPF	PSEN2	psi-mi:“MI:0915”(physical association)	0.370
LIPF	MPZL1	psi-mi:“MI:0914”(association)	0.350
NTNG1	AMY1A	psi-mi:“MI:0914”(association)	0.350

BioGRID (26): LRSAM1 (Affinity Capture-MS), TCN2 (Affinity Capture-MS), RNF31 (Affinity Capture-MS), SHARPIN (Affinity Capture-MS), MPZL1 (Affinity Capture-MS), BRAF (Affinity Capture-MS), LRSAM1 (Affinity Capture-MS), RNF31 (Affinity Capture-MS), SHARPIN (Affinity Capture-MS), MPZL1 (Affinity Capture-MS), BRAF (Affinity Capture-MS), NPTX1 (Affinity Capture-MS), LIPF (Two-hybrid), MPZL1 (Affinity Capture-MS), RNF31 (Affinity Capture-MS)

ESM2 similar proteins: A5D6U8, A6H730, J3SDX8, O16956, O35409, O61866, O75795, P04068, P04634, P07098, P07099, P07687, P08430, P0DTE5, P11515, P19224, P21529, P36510, P37891, P38571, P49614, P70627, P70691, P79381, P80035, Q28611, Q29458, Q38924, Q3U4B4, Q3YBN2, Q41005, Q4R4S5, Q5VXI9, Q5VXJ0, Q5VYY2, Q5W064, Q64194, Q64435, Q64550, Q67ZU1

Diamond homologs: J3SDX8, O16956, O46107, O46108, O61866, O74430, P04634, P07098, P34163, P38571, P78898, P80035, Q29458, Q3U4B4, Q3YBN2, Q4R4S5, Q5VXI9, Q5VXJ0, Q5VYY2, Q5W064, Q64194, Q67ZU1, Q8BM14, Q8K2A6, Q93789, Q94252, Q9CPP7, Q9Z0M5, Q07950, Q71DJ5, O60095, Q07804

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

52 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1483 predictions. Top by Δscore:

Variant	Effect	Δscore
10:88665560:G:GG	donor_gain	1.0000
10:88665565:T:G	donor_gain	1.0000
10:88667286:GGC:G	acceptor_gain	1.0000
10:88667286:GGCA:G	acceptor_gain	1.0000
10:88667398:ACATT:A	donor_gain	1.0000
10:88667399:CATT:C	donor_gain	1.0000
10:88667400:ATT:A	donor_gain	1.0000
10:88667401:TT:T	donor_gain	1.0000
10:88667403:G:GG	donor_gain	1.0000
10:88667558:T:TA	acceptor_gain	1.0000
10:88667565:TCA:T	acceptor_loss	1.0000
10:88667567:A:AC	acceptor_loss	1.0000
10:88667567:A:AG	acceptor_gain	1.0000
10:88667568:G:GG	acceptor_gain	1.0000
10:88667568:GA:G	acceptor_gain	1.0000
10:88667568:GAGTC:G	acceptor_gain	1.0000
10:88667685:AGGT:A	donor_loss	1.0000
10:88667687:G:GG	donor_gain	1.0000
10:88667688:T:G	donor_loss	1.0000
10:88669832:TTCA:T	acceptor_loss	1.0000
10:88669833:TCAG:T	acceptor_loss	1.0000
10:88669834:CAGC:C	acceptor_loss	1.0000
10:88669835:A:AG	acceptor_gain	1.0000
10:88669836:G:GA	acceptor_gain	1.0000
10:88669836:GC:G	acceptor_gain	1.0000
10:88669836:GCT:G	acceptor_gain	1.0000
10:88669836:GCTT:G	acceptor_gain	1.0000
10:88669836:GCTTT:G	acceptor_gain	1.0000
10:88669942:CATTG:C	donor_gain	1.0000
10:88669943:ATTG:A	donor_gain	1.0000

AlphaMissense

2658 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:88668752:T:C	F140L	0.998
10:88668754:C:A	F140L	0.998
10:88668754:C:G	F140L	0.998
10:88669928:T:C	S172P	0.998
10:88668674:T:A	W114R	0.996
10:88668674:T:C	W114R	0.996
10:88668690:G:C	R119T	0.996
10:88668691:A:C	R119S	0.996
10:88668691:A:T	R119S	0.996
10:88678511:G:C	D343H	0.996
10:88668690:G:T	R119I	0.994
10:88668743:T:C	F137L	0.994
10:88668745:C:A	F137L	0.994
10:88668745:C:G	F137L	0.994
10:88675649:T:A	W294R	0.994
10:88675649:T:C	W294R	0.994
10:88678512:A:C	D343A	0.994
10:88675629:C:T	S287F	0.993
10:88678512:A:T	D343V	0.993
10:88668611:T:A	W93R	0.992
10:88668611:T:C	W93R	0.992
10:88675590:G:C	R274P	0.992
10:88669859:G:C	D149H	0.991
10:88678600:C:A	H372Q	0.991
10:88678600:C:G	H372Q	0.991
10:88678605:A:T	D374V	0.991
10:88668635:A:C	S101R	0.990
10:88668637:C:A	S101R	0.990
10:88668637:C:G	S101R	0.990
10:88668755:A:C	S141R	0.990

dbSNP variants (sampled 300 via entrez): RS1000153663 (10:88670577 A>T), RS1000542651 (10:88676422 T>A,G), RS1000974982 (10:88676739 G>C,T), RS1001095907 (10:88670008 G>A), RS1001178331 (10:88663047 G>T), RS1001210658 (10:88669016 G>A), RS1001322124 (10:88677063 C>T), RS1001458511 (10:88663291 G>A), RS1001798826 (10:88672622 A>G), RS1001910333 (10:88670969 A>G), RS1001963947 (10:88672363 G>A), RS1002093021 (10:88666132 T>C), RS1002097091 (10:88675851 A>C), RS1002098200 (10:88671458 G>A,T), RS1002277826 (10:88675442 A>G)

Disease associations

OMIM: gene MIM:601980 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST007495_2	Estimated glomerular filtration rate in coronary artery disease and impaired kidney function	6.000000e-08
GCST008759_10	Intake of total sugars	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010158	sugar consumption measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1796 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — 3.1.1.- Carboxylic Ester Hydrolases

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Orlistat	decreases activity	2
Acetaminophen	increases expression	1
Benzo(a)pyrene	increases methylation	1
Triglycerides	affects hydrolysis	1
Valproic Acid	decreases methylation	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL680753	Binding	Inhibition constant (molar fraction of compound) on human gastric lipase (HGL) at a constant surface pressure of 17 mM/m	Triacylglycerols based on 2-(N-tert-butoxycarbonylamino)oleic acid are potent inhibitors of pancreatic lipase. — J Med Chem

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.