APOF

Summary

APOF (apolipoprotein F, HGNC:615) is a protein-coding gene on chromosome 12q13.3, encoding Apolipoprotein F (Q13790). Minor apolipoprotein that associates with LDL.

The product of this gene is one of the minor apolipoproteins found in plasma. This protein forms complexes with lipoproteins and may be involved in transport and/or esterification of cholesterol.

Source: NCBI Gene 319 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 45 total
• MANE Select transcript: NM_001638

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:615
Approved symbol	APOF
Name	apolipoprotein F
Location	12q13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000175336
Ensembl biotype	protein_coding
OMIM	107760
Entrez	319

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000398189, ENST00000887741, ENST00000887742

RefSeq mRNA: 1 — MANE Select: NM_001638 NM_001638

CCDS: CCDS44923

Canonical transcript exons

ENST00000398189 — 2 exons

Exon	Start	End
ENSE00001658798	56360568	56362189
ENSE00003512571	56362730	56362857

Expression profiles

Bgee: expression breadth broad, 32 present calls, max score 98.13.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.9358 / max 564.1410, expressed in 14 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
131521	0.8407	14
131522	0.0950	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	98.13	gold quality
liver	UBERON:0002107	96.47	gold quality
endometrium epithelium	UBERON:0004811	52.99	gold quality
granulocyte	CL:0000094	51.94	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
oviduct epithelium	UBERON:0004804	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
quadriceps femoris	UBERON:0001377	49.97	gold quality
thymus	UBERON:0002370	49.53	gold quality
vastus lateralis	UBERON:0001379	49.45	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cerebellar vermis	UBERON:0004720	49.25	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
islet of Langerhans	UBERON:0000006	49.06	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
epithelial cell of pancreas	CL:0000083	48.61	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
cervix epithelium	UBERON:0004801	48.04	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	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

Upstream regulators (CollecTRI, top): MIER1, NR1H4

miRNA regulators (miRDB)

15 targeting APOF, 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-4282	99.99	75.36	6408
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-4709-3P	98.88	68.04	1594
HSA-MIR-655-5P	98.74	65.93	888
HSA-MIR-4726-3P	98.49	63.89	1385
HSA-MIR-660-3P	98.14	66.04	1434
HSA-MIR-376A-5P	97.70	65.61	863
HSA-MIR-4430	97.47	65.61	1813
HSA-MIR-6822-3P	96.60	66.06	680
HSA-MIR-6879-3P	93.93	64.00	759

Literature-anchored findings (GeneRIF, showing 9)

• LTIP tailors CETP-mediated remodeling of HDL3 and HDL2 particles in subclass-specific ways, strongly implicating it as a regulator of HDL metabolism (PMID:12907677)
• we have confirmed the negative association between plasma triglyceride levels and Apolipoprotein F previously suggested by a small data set, but now we demonstrate that this effect is seen only in males. (PMID:17901467)
• lipoprotein composition may influence the status of lipid transfer inhibitor protein activity (PMID:18369235)
• LTIP translocation is dependent on LDL lipid composition (PMID:21937674)
• this study has identified apoF as likely another target gene of FXR. (PMID:24211198)
• Direct interactions between C/EBPalpha and ETS-1 were important for high liver-specific expression of ApoF. (PMID:25726912)
• Apolipoprotein F concentration, activity, and the properties of LDL controlling ApoF activation in hyperlipidemic plasma. (PMID:35016907)
• Apolipoprotein F is reduced in humans with steatosis and controls plasma triglyceride-rich lipoprotein metabolism. (PMID:35735979)
• A pan-cancer analysis of the oncogenic and immunological roles of apolipoprotein F (APOF) in human cancer. (PMID:37312170)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	apof	ENSDARG00000090980
mus_musculus	Apof	ENSMUSG00000047631
rattus_norvegicus	Apof	ENSRNOG00000062320

Protein

Protein identifiers

Apolipoprotein F — Q13790 (reviewed: Q13790)

Alternative names: Lipid transfer inhibitor protein

All UniProt accessions (1): Q13790

UniProt curated annotations — full annotation on UniProt →

Function. Minor apolipoprotein that associates with LDL. Inhibits cholesteryl ester transfer protein (CETP) activity and appears to be an important regulator of cholesterol transport. Also associates to a lesser degree with VLDL, Apo-AI and Apo-AII.

Subcellular location. Secreted.

Tissue specificity. Expressed by the liver and secreted in plasma.

Post-translational modifications. O-glycosylated with core 1 or possibly core 8 glycans.

Similarity. Belongs to the apolipoprotein F family.

RefSeq proteins (1): NP_001629* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026114	APOF	Family

Pfam: PF15148

UniProt features (7 total): glycosylation site 2, signal peptide 1, propeptide 1, chain 1, modified residue 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13790-F1	66.68	0.25

Functional residue map

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

Post-translational modifications (1): 323

Glycosylation sites (2): 118, 274

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-8964041	LDL remodeling
R-HSA-174824	Plasma lipoprotein assembly, remodeling, and clearance
R-HSA-382551	Transport of small molecules
R-HSA-8963899	Plasma lipoprotein remodeling

MSigDB gene sets: 100 (showing top): GNF2_GSTM1, GNF2_HPN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_CHOLESTEROL_EFFLUX, GNF2_LCAT, HSIAO_LIVER_SPECIFIC_GENES, CAIRO_HEPATOBLASTOMA_DN, GOBP_LIPID_METABOLIC_PROCESS, GNF2_HPX, GOBP_NEUTRAL_LIPID_METABOLIC_PROCESS, GOBP_STEROL_TRANSPORT, GOMF_SIGNALING_RECEPTOR_BINDING

GO Biological Process (6): lipid metabolic process (GO:0006629), triglyceride metabolic process (GO:0006641), lipid transport (GO:0006869), cholesterol metabolic process (GO:0008203), cholesterol efflux (GO:0033344), steroid metabolic process (GO:0008202)

GO Molecular Function (4): signaling receptor binding (GO:0005102), lipid carrier activity (GO:0005319), cholesterol binding (GO:0015485), protein binding (GO:0005515)

GO Cellular Component (4): obsolete extracellular space (GO:0005615), low-density lipoprotein particle (GO:0034362), high-density lipoprotein particle (GO:0034364), extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Plasma lipoprotein remodeling	1
Transport of small molecules	1
Plasma lipoprotein assembly, remodeling, and clearance	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
plasma lipoprotein particle	2
primary metabolic process	1
acylglycerol metabolic process	1
transport	1
lipid localization	1
sterol metabolic process	1
secondary alcohol metabolic process	1
cholesterol transport	1
lipid metabolic process	1
protein binding	1
molecular carrier activity	1
sterol binding	1
alcohol binding	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

774 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
APOF	CETP	P11597	927
APOF	APOL1	O14791	854
APOF	APOD	P05090	805
APOF	APOA4	P06727	802
APOF	CLU	P10909	773
APOF	APOH	P02749	765
APOF	APOM	O95445	765
APOF	APOC3	P02656	739
APOF	APOA1	P02647	729
APOF	PLTP	P55058	726
APOF	APOE	P02649	719
APOF	PON1	P27169	717
APOF	APOA2	P02652	711
APOF	APOA5	Q6Q788	637
APOF	APOC4	P55056	602

IntAct

4 interactions, top by confidence:

A	B	Type	Score
APOF	GALNT4	psi-mi:“MI:0915”(physical association)	0.590
APOF	GAPDHS	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (6): GALNT4 (Affinity Capture-MS), GALNT4 (Affinity Capture-MS), APOA2 (Co-purification), APOA1 (Co-purification), GALNT4 (Affinity Capture-MS), GAPDHS (Affinity Capture-MS)

ESM2 similar proteins: A0A096P2H6, A0A0D9S1R4, A2APA5, A9CBA0, P06740, P06759, P0DKU6, P0DKW1, P0DKW2, P0DKW3, P0DKW4, P0DKY3, P0DML4, P0DML5, P0DML6, P0DMN8, P0DOC4, P0DP53, P0DTG9, P0DTH0, P0DTH1, P0DTH2, P0DTH3, P0DTH4, P0DUP5, P0DUP6, P22749, P33622, P35225, P55056, P55057, P55797, Q0VCT2, Q13790, Q3SYR5, Q3ZRW9, Q5HZE8, Q5JTB6, Q5JX69, Q5JX71

Diamond homologs: Q13790, Q5M889, Q91V80

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	42
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

132 predictions. Top by Δscore:

Variant	Effect	Δscore
12:56362760:G:GA	donor_gain	0.9800
12:56362781:T:TA	donor_gain	0.9400
12:56362729:C:CT	donor_gain	0.9300
12:56362188:CC:C	acceptor_gain	0.9000
12:56362189:CC:C	acceptor_gain	0.9000
12:56362758:C:CT	donor_gain	0.9000
12:56362759:T:TT	donor_gain	0.9000
12:56362737:T:TA	donor_gain	0.8500
12:56362186:TACC:T	acceptor_gain	0.8300
12:56362729:CCACA:C	donor_gain	0.8100
12:56362188:CCCTA:C	acceptor_loss	0.8000
12:56362191:T:A	acceptor_loss	0.8000
12:56362729:CCA:C	donor_gain	0.8000
12:56362735:AGT:A	donor_gain	0.7900
12:56362190:C:CC	acceptor_gain	0.7800
12:56362192:A:C	acceptor_loss	0.7300
12:56362086:T:A	donor_gain	0.7200
12:56362185:GTACC:G	acceptor_gain	0.7000
12:56362723:AAATT:A	donor_loss	0.7000
12:56362724:AATT:A	donor_loss	0.7000
12:56362725:ATT:A	donor_loss	0.7000
12:56362726:TTA:T	donor_loss	0.7000
12:56362727:T:A	donor_loss	0.7000
12:56362729:C:T	donor_loss	0.7000
12:56362187:ACC:A	acceptor_gain	0.6900
12:56362188:CCC:C	acceptor_gain	0.6900
12:56362730:C:G	donor_loss	0.6900
12:56362190:C:T	acceptor_gain	0.6700
12:56362674:CAGG:C	donor_gain	0.6700
12:56362730:C:CT	donor_gain	0.6600

AlphaMissense

2085 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:56361978:G:C	F76L	0.987
12:56361978:G:T	F76L	0.987
12:56361980:A:G	F76L	0.987
12:56361951:G:C	F85L	0.976
12:56361951:G:T	F85L	0.976
12:56361953:A:G	F85L	0.976
12:56361588:G:C	C206W	0.974
12:56361589:C:G	C206S	0.974
12:56361590:A:T	C206S	0.974
12:56361614:C:G	A198P	0.973
12:56361907:C:G	C100S	0.970
12:56361908:A:T	C100S	0.970
12:56361979:A:C	F76C	0.970
12:56361602:C:G	A202P	0.969
12:56361629:A:C	Y193D	0.967
12:56361934:A:G	L91P	0.967
12:56361568:C:G	R213P	0.966
12:56361619:C:T	G196D	0.966
12:56361532:A:G	L225P	0.965
12:56361608:A:C	Y200D	0.965
12:56361952:A:C	F85C	0.965
12:56361590:A:G	C206R	0.962
12:56361922:A:G	L95P	0.961
12:56361908:A:G	C100R	0.960
12:56361468:T:A	K246N	0.956
12:56361468:T:G	K246N	0.956
12:56361472:A:G	L245P	0.955
12:56361544:A:G	L221P	0.954
12:56361620:C:G	G196R	0.954
12:56361826:A:G	L127P	0.954

dbSNP variants (sampled 300 via entrez): RS1000164732 (12:56362395 G>A), RS1001228611 (12:56362101 A>G), RS1001243556 (12:56364673 A>T), RS1001608340 (12:56361604 T>C), RS1001619806 (12:56361975 G>A,C), RS1003279035 (12:56360180 C>A,T), RS1003290699 (12:56360329 T>C), RS1003713526 (12:56360444 C>G), RS1004685950 (12:56363082 G>A,T), RS1004957938 (12:56363969 C>A,T), RS1005143541 (12:56363511 A>G), RS1005814518 (12:56360165 T>C), RS1006767357 (12:56361152 A>G), RS1007844365 (12:56360430 A>T), RS1009348332 (12:56360607 A>G,T)

Disease associations

OMIM: gene MIM:107760 | 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
GCST002115_16	Axial length	4.000000e-07
GCST006585_1385	Blood protein levels	7.000000e-16

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005318	axial length measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	affects cotreatment, affects expression, decreases expression	2
lasiocarpine	decreases expression	1
bisphenol A	affects expression	1
chlortoluron	decreases expression	1
sodium arsenite	increases expression	1
tebuconazole	decreases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Calcitriol	increases expression, affects cotreatment	1
Chlorpromazine	affects expression, affects cotreatment	1
Cholic Acids	affects expression, affects cotreatment	1
Niclosamide	decreases expression	1
Quercetin	decreases expression	1
Testosterone	affects cotreatment, increases expression	1
Urethane	decreases expression	1
Valproic Acid	decreases expression, increases methylation	1
1-Naphthylisothiocyanate	affects cotreatment, affects expression	1
Aflatoxin B1	decreases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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