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
• Expression (HPA): Tissue enriched — highest in stomach 1, duodenum, kidney
• GTEx eGene: eQTL in 5 tissues, sQTL in 0 (q < 0.05)
• Drug target: yes — 2 curated mechanism-of-action drugs
• Approved drugs (ChEMBL mechanism of action): 1 — Orlistat
• Constraint (gnomAD): pLI 0.01 (LoF-tolerant), LOEUF 1.14 (unconstrained)
• MANE Select transcript: NM_004190
• Notable: 52 clinical variants but no curated precision-oncology (CIViC) evidence yet

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

MANE Select: ENST00000238983

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 3

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
ENSE00004788964	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.

Highest expression (Bgee): cardia of stomach, pylorus, body of stomach, stomach, uterine tube.

Genetic regulation across tissues (GTEx eQTL / sQTL)

LIPF is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 5 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

5 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Muscle Skeletal	eqtl	1.1e-03	+0.24	10:88489188:A:C
Prostate	eqtl	2.2e-02	+0.44	10:89307681:T:C
Lung	eqtl	2.5e-02	+0.71	10:89451015:T:C
Whole Blood	eqtl	3.5e-02	-0.24	10:89454178:A:G
Artery Tibial	eqtl	3.7e-02	+0.81	10:88980025:G:A

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
106057	5.2474	11

Top tissues by expression

showing 100 of 285 tissues 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
esophagogastric junction muscularis propria	UBERON:0035841	64.91	gold quality
thoracic aorta	UBERON:0001515	64.76	gold quality
adenohypophysis	UBERON:0002196	64.57	gold quality
body of uterus	UBERON:0009853	64.40	gold quality
ascending aorta	UBERON:0001496	64.37	gold quality
small intestine Peyer’s patch	UBERON:0003454	64.02	gold quality
esophagus	UBERON:0001043	63.69	gold quality
left adrenal gland cortex	UBERON:0035825	63.27	gold quality
descending thoracic aorta	UBERON:0002345	63.20	gold quality
uterine cervix	UBERON:0000002	62.85	gold quality
colonic epithelium	UBERON:0000397	62.61	gold quality
right testis	UBERON:0004534	62.24	gold quality
lower esophagus muscularis layer	UBERON:0035833	62.24	gold quality
lower esophagus	UBERON:0013473	62.22	gold quality
right hemisphere of cerebellum	UBERON:0014890	62.22	gold quality
left testis	UBERON:0004533	62.07	gold quality
small intestine	UBERON:0002108	61.60	gold quality
adrenal cortex	UBERON:0001235	60.93	gold quality
coronary artery	UBERON:0001621	60.93	gold quality
vagina	UBERON:0000996	60.89	gold quality
left coronary artery	UBERON:0001626	60.59	gold quality
testis	UBERON:0000473	59.61	gold quality
right adrenal gland cortex	UBERON:0035827	59.52	gold quality
minor salivary gland	UBERON:0001830	59.50	gold quality
metanephros	UBERON:0000081	58.69	gold quality
adrenal gland	UBERON:0002369	58.62	gold quality
ovary	UBERON:0000992	58.53	gold quality
muscle layer of sigmoid colon	UBERON:0035805	58.35	gold quality
pancreas	UBERON:0001264	57.94	gold quality
gastrocnemius	UBERON:0001388	57.83	gold quality
aorta	UBERON:0000947	57.65	gold quality
omental fat pad	UBERON:0010414	57.02	gold quality
mouth mucosa	UBERON:0003729	56.99	gold quality
peritoneum	UBERON:0002358	56.97	gold quality
intestine	UBERON:0000160	56.85	gold quality
colon	UBERON:0001155	56.84	gold quality
decidua	UBERON:0002450	56.55	gold quality
adipose tissue of abdominal region	UBERON:0007808	56.12	gold quality
large intestine	UBERON:0000059	55.88	gold quality
fallopian tube	UBERON:0003889	55.55	gold quality
prostate gland	UBERON:0002367	55.50	gold quality
sigmoid colon	UBERON:0001159	55.03	gold quality
left lobe of thyroid gland	UBERON:0001120	54.78	gold quality
saliva-secreting gland	UBERON:0001044	54.58	gold quality
skin of abdomen	UBERON:0001416	54.44	gold quality
adult mammalian kidney	UBERON:0000082	53.69	gold quality
muscle of leg	UBERON:0001383	53.27	gold quality
cerebellar hemisphere	UBERON:0002245	53.15	gold quality
female reproductive system	UBERON:0000474	52.99	gold quality
cerebellar cortex	UBERON:0002129	52.93	gold quality
heart left ventricle	UBERON:0002084	52.67	gold quality
right atrium auricular region	UBERON:0006631	52.64	gold quality
tibial artery	UBERON:0007610	52.57	gold quality
popliteal artery	UBERON:0002250	52.49	gold quality
hair follicle	UBERON:0002073	52.43	gold quality
cardiac atrium	UBERON:0002081	52.41	gold quality
cardiac ventricle	UBERON:0002082	52.25	gold quality
anatomical system	UBERON:0000467	52.09	gold quality
thyroid gland	UBERON:0002046	52.09	gold quality
cerebellum	UBERON:0002037	52.02	gold quality
material anatomical entity	UBERON:0000465	51.81	gold quality
multicellular organism	UBERON:0000468	51.79	gold quality
muscle organ	UBERON:0001630	51.67	gold quality
Brodmann (1909) area 10	UBERON:0013541	51.61	gold quality
myometrium	UBERON:0001296	51.44	gold quality
heart	UBERON:0000948	51.28	gold quality
epithelium of esophagus	UBERON:0001976	51.13	silver quality
skin of leg	UBERON:0001511	50.97	gold quality
zone of skin	UBERON:0000014	50.68	gold quality
ventral tegmental area	UBERON:0002691	50.47	silver 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

HPA expression

RNA tissue specificity: Tissue enriched

22 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Stomach 1	tissue	24713.1	high
Duodenum	tissue	247.4	not detected
Kidney	tissue	10.7	not detected
Colon	tissue	8.0	not detected
Olfactory bulb	tissue	7.6
Prostate	tissue	6.3	not detected
Pituitary gland	tissue	6.2
Vagina	tissue	2.1	not detected
Ovary	tissue	0.9	not detected
Spleen	tissue	0.9	not detected
Testis	tissue	0.7	not detected
Medulla oblongata	tissue	0.6
Placenta	tissue	0.5	not detected
Fallopian tube	tissue	0.3	not detected
Lung	tissue	0.2	not detected
Choroid plexus	tissue	0.1
Thyroid gland	tissue	0.1	not detected
Liver	tissue	0.1	not detected
Small intestine	tissue	0.1	not detected
Locus coeruleus	tissue	0.1
Spinal cord	tissue	0.1
Tonsil	tissue	0.1	not detected

Brain sub-regions (HPA Brain Atlas): detected in 21; highest nTPM — Blood vessel (1.9), Nucleus tractus solitarii (0.6), Dorsal raphe nucleus (0.3), Periaquaductal grey, dorsal (0.3), Periaquaductal grey, lateral (0.3).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting LIPF by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

9 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 0.00712, LOEUF 1.14, missense Z 0.683 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000238983 — one region, missense o/e 0.87.

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)

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Macaca fascicularis	Q4R4S5	98.0%	Diamond
Canis lupus familiaris	P80035	85.4%	Diamond
Bos taurus	Q29458	73.1%	Diamond
Crotalus adamanteus	J3SDX8	67.4%	Diamond
Mesocricetus auratus	Q3YBN2	50.7%	Diamond
Schizosaccharomyces pombe 972h-	O74430	50.1%	Diamond
Saccharomyces cerevisiae S288C	P34163	50.0%	Diamond
Arabidopsis thaliana	Q71DJ5	38.3%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
LIPJ	protein-coding	142910
LIPK	protein-coding	643414
LIPN	protein-coding	643418
RNLS	protein-coding	55328

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)

• 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 structure by resolution:

PDB	Title	Method	Resolution (Å)
1HLG	CRYSTAL STRUCTURE OF HUMAN GASTRIC LIPASE	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Metabolic proteins, Predicted secreted proteins, FDA approved drug targets, Small molecule drugs

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH enhanced

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)

Position	Role
172	nucleophile
343	charge relay system
372	charge relay system

Disulfide bonds (1)

Type	Positions
Disulfide bond	246–255

Glycosylation sites (4)

Type	Positions
N-linked (glcnac…) asparagine	34, 99, 271, 327

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 3; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

3 pathways:

ID	Pathway	Evidence
R-HSA-192456	Digestion of dietary lipid	curated
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 (3): 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

2 top-level categories:

Category	Pathways
Digestion	1
Digestion and absorption	1

GO top-level categories

14 GO namespaces:

Category	Terms
binding	2
hydrolase activity, acting on ester bonds	2
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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 13 annotations. The rest are phylogenetic / computational / electronic (IEA).

1 experimentally-supported GO terms:

GO term	NS	Evidence
triacylglycerol lipase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,046 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LIPF	PNLIP	P16233	976
LIPF	CLPS	P04118	938
LIPF	PNLIPRP1	P54315	917
LIPF	LIPC	P11150	797
LIPF	LPL	P06858	721
LIPF	PGA4	P00790	570
LIPF	SCGB1D2	O95969	552
LIPF	PGA4	P00790	540
LIPF	GKN1	Q9NS71	538
LIPF	CEL	P19835	504
LIPF	PGA4	P00790	492
LIPF	LTF	P02788	467
LIPF	PNLIPRP3	Q17RR3	457
LIPF	HLA-DOA	P06340	445
LIPF	AMY1B	P04745	443

IntAct

Human interaction partners of LIPF in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

2 partners by confidence:

Partner	Interaction type	MIscore	Records
LRSAM1	physical association	0.500	1
PSEN2	physical association	0.370	1

BioGRID (26 interactions; top human partners by supporting records): BRAF (Affinity Capture-MS; 3 records), LRSAM1 (Affinity Capture-MS; 3 records), MPZL1 (Affinity Capture-MS; 3 records), RNF31 (Affinity Capture-MS; 3 records), SHARPIN (Affinity Capture-MS; 3 records), ATP4A (Affinity Capture-MS), MEOX2 (Two-hybrid), NGLY1 (Affinity Capture-MS), NPTX1 (Affinity Capture-MS), NTNG1 (Affinity Capture-MS), PSEN2 (Two-hybrid), TCN2 (Affinity Capture-MS)

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexe by size:

Complex	Subunits	Members
★ LIPF homodimer	1	LIPF

Disease & clinical

Genetic variants

Variant evidence for LIPF: 52 ClinVar records (0 pathogenic / likely pathogenic); 2 GWAS associations.

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

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 31 predictions of 922):

Position(s)	Effect	Δscore	Sites
10:88665565	donor_gain	1.0000
10:88667567–88667568	acceptor_loss	1.0000	6
10:88667687–88667688	donor_loss	1.0000	4
10:88669835–88669836	acceptor_loss	1.0000	4
10:88669947–88669948	donor_loss	1.0000	5
10:88676194	acceptor_gain	1.0000
10:88676203	acceptor_gain	1.0000
10:88676207–88676208	acceptor_loss	1.0000	4
10:88676208	acceptor_gain	1.0000
10:88676281–88676282	donor_loss	1.0000	4

AlphaMissense

892 missense substitutions predicted likely pathogenic (of 2,658 scored), across 238 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D343	8	0.988	0.996
H372	8	0.981	0.991
D149	8	0.979	0.991
D374	8	0.975	0.991
D350	8	0.953	0.987
H84	8	0.952	0.978
D55	8	0.936	0.980
D112	8	0.928	0.958
H293	8	0.928	0.981
N314	8	0.908	0.954
H171	8	0.907	0.980
F182	8	0.857	0.943
F140	7	0.977	0.998
W114	7	0.976	0.996
F137	7	0.975	0.994
W93	7	0.969	0.992
W294	7	0.967	0.994
C255	7	0.953	0.976
F375	7	0.951	0.988
C246	7	0.948	0.978

HPA cancer prognostics

RNA cancer specificity: Cancer enriched (Stomach Adenocarcinoma)

Disease associations

OMIM: gene MIM:601980 | disease phenotypes:

GWAS associations

2 associations:

Study	Trait	p-value
GCST007495_2	Estimated glomerular filtration rate in coronary artery disease and impaired kidney function	6e-8
GCST008759_10	Intake of total sugars	4e-6

EFO canonical traits (from GWAS)

1 canonical traits:

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)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the LIPF protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

2 curated-mechanism drugs:

Drug	Modality	Max phase
ORLISTAT	Small molecule	4
CETILISTAT	Small molecule	2

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — 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)

Via MONDO — disease-level, not drug-specific.