APOL3

Summary

APOL3 (apolipoprotein L3, HGNC:14868) is a protein-coding gene on chromosome 22q12.3, encoding Apolipoprotein L3 (O95236). May affect the movement of lipids in the cytoplasm or allow the binding of lipids to organelles.

This gene is a member of the apolipoprotein L gene family, and it is present in a cluster with other family members on chromosome 22. The encoded protein is found in the cytoplasm, where it may affect the movement of lipids, including cholesterol, and/or allow the binding of lipids to organelles. In addition, expression of this gene is up-regulated by tumor necrosis factor-alpha in endothelial cells lining the normal and atherosclerotic iliac artery and aorta. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 80833 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 87 total
• MANE Select transcript: NM_145639

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14868
Approved symbol	APOL3
Name	apolipoprotein L3
Location	22q12.3
Locus type	gene with protein product
Status	Approved
Aliases	CG12-1, APOLIII
Ensembl gene	ENSG00000128284
Ensembl biotype	protein_coding
OMIM	607253
Entrez	80833

Gene structure

Transcript identifiers

Ensembl transcripts: 38 — 30 protein_coding, 4 nonsense_mediated_decay, 4 protein_coding_CDS_not_defined

ENST00000349314, ENST00000361710, ENST00000397287, ENST00000397289, ENST00000422426, ENST00000424878, ENST00000426939, ENST00000432700, ENST00000472303, ENST00000485453, ENST00000487355, ENST00000487423, ENST00000487783, ENST00000525184, ENST00000528740, ENST00000530895, ENST00000531095, ENST00000531195, ENST00000533061, ENST00000534251, ENST00000695564, ENST00000857486, ENST00000857487, ENST00000857488, ENST00000857489, ENST00000857490, ENST00000857491, ENST00000857492, ENST00000857493, ENST00000857494, ENST00000857495, ENST00000857496, ENST00000955239, ENST00000955240, ENST00000955241, ENST00000955242, ENST00000955243, ENST00000955244

RefSeq mRNA: 28 — MANE Select: NM_145639 NM_001393587, NM_001393588, NM_001393589, NM_001393590, NM_001393591, NM_001393592, NM_001393593, NM_001393595, NM_001393596, NM_001393597, NM_001393598, NM_001393599, NM_001393600, NM_001393601, NM_001393602, NM_001393603, NM_001393604, NM_001393605, NM_001393606, NM_001393607, NM_001393608, NM_001393609, NM_014349, NM_030644, NM_145639, NM_145640, NM_145641, NM_145642

CCDS: CCDS13922, CCDS13923, CCDS13924

Canonical transcript exons

ENST00000424878 — 4 exons

Exon	Start	End
ENSE00003598776	36145473	36145599
ENSE00003630466	36149046	36149142
ENSE00003684094	36140329	36142058
ENSE00003964295	36160669	36160755

Expression profiles

Bgee: expression breadth ubiquitous, 274 present calls, max score 97.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.1378 / max 404.2073, expressed in 1022 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
193863	6.2500	687
193864	2.0215	620
193862	0.8663	561

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	97.90	gold quality
monocyte	CL:0000576	97.82	gold quality
mononuclear cell	CL:0000842	97.59	gold quality
leukocyte	CL:0000738	97.53	gold quality
apex of heart	UBERON:0002098	97.22	gold quality
mucosa of stomach	UBERON:0001199	96.96	gold quality
pericardium	UBERON:0002407	96.78	gold quality
lymph node	UBERON:0000029	96.61	gold quality
spleen	UBERON:0002106	96.56	gold quality
subcutaneous adipose tissue	UBERON:0002190	96.56	gold quality
right lung	UBERON:0002167	96.44	gold quality
omental fat pad	UBERON:0010414	96.16	gold quality
peritoneum	UBERON:0002358	96.14	gold quality
tendon of biceps brachii	UBERON:0008188	95.84	gold quality
upper lobe of left lung	UBERON:0008952	95.71	gold quality
adipose tissue of abdominal region	UBERON:0007808	95.66	gold quality
colonic epithelium	UBERON:0000397	95.64	gold quality
left uterine tube	UBERON:0001303	95.58	gold quality
upper lobe of lung	UBERON:0008948	95.24	gold quality
calcaneal tendon	UBERON:0003701	95.17	gold quality
tibial nerve	UBERON:0001323	95.04	gold quality
sural nerve	UBERON:0015488	94.85	gold quality
vermiform appendix	UBERON:0001154	94.84	gold quality
caecum	UBERON:0001153	94.28	gold quality
tendon	UBERON:0000043	94.23	gold quality
adipose tissue	UBERON:0001013	94.19	gold quality
body of uterus	UBERON:0009853	93.99	gold quality
right lobe of thyroid gland	UBERON:0001119	93.93	gold quality
connective tissue	UBERON:0002384	93.86	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.66	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.16
E-GEOD-99795	no	167.51

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

44 targeting APOL3, 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-6740-5P	100.00	65.64	932
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-20A-3P	99.44	69.10	1575
HSA-MIR-6839-3P	99.39	68.86	1301
HSA-MIR-4999-5P	99.35	69.15	926
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-6504-5P	99.26	65.95	1487
HSA-MIR-5690	99.25	67.58	1012
HSA-MIR-3978	99.24	68.39	2201
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-320A-5P	98.88	66.75	1248
HSA-MIR-4763-5P	98.75	63.89	854
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-1537-5P	98.70	68.33	999
HSA-MIR-4718	98.55	68.61	814
HSA-MIR-6884-3P	98.05	65.32	750
HSA-MIR-6801-3P	98.04	64.64	805
HSA-MIR-6810-3P	97.96	64.57	1023
HSA-MIR-6893-3P	97.79	64.91	1238
HSA-MIR-6787-3P	97.75	66.17	1233

Literature-anchored findings (GeneRIF, showing 8)

• APOL3 has been found only in humans and African green monkeys (PMID:11944986)
• An association between an single nucleotide polymorphisms within the APOL3 locus and prostate cancer risk, is revealed. (PMID:20631155)
• A null variant in the apolipoprotein L3 gene is associated with non-diabetic nephropathy. (PMID:28339911)
• APOL3 regulates angiogenesis in vitro and functions as a modulator of MAPK and FAK signaling in endothelial cells. (PMID:30423477)
• APOL1 C-Terminal Variants May Trigger Kidney Disease through Interference with APOL3 Control of Actomyosin. (PMID:32187552)
• The function of apolipoproteins L (APOLs): relevance for kidney disease, neurotransmission disorders, cancer and viral infection. (PMID:32530132)
• A human apolipoprotein L with detergent-like activity kills intracellular pathogens. (PMID:34437126)
• Apolipoprotein L3 enhances CD8+ T cell antitumor immunity of colorectal cancer by promoting LDHA-mediated ferroptosis. (PMID:36923931)

Cross-species orthologs

13 orthologs

Organism	Symbol	Gene ID
danio_rerio	apol	ENSDARG00000073718
mus_musculus	Apol10b	ENSMUSG00000050014
mus_musculus	Apol10a	ENSMUSG00000050982
mus_musculus	Apol9a	ENSMUSG00000057346
mus_musculus	Apol9b	ENSMUSG00000068246
mus_musculus	Apol11a	ENSMUSG00000091650
mus_musculus	Apol11b	ENSMUSG00000091694
rattus_norvegicus	Apol9a	ENSRNOG00000023410
rattus_norvegicus	Apol3l1	ENSRNOG00000042771
rattus_norvegicus	LOC120093819	ENSRNOG00000069032
rattus_norvegicus		ENSRNOG00000081988
caenorhabditis_elegans		WBGENE00017219
caenorhabditis_elegans		WBGENE00017220

Paralogs (6): APOL4 (ENSG00000100336), APOL1 (ENSG00000100342), APOL5 (ENSG00000128313), APOL2 (ENSG00000128335), APOLD1 (ENSG00000178878), APOL6 (ENSG00000221963)

Protein

Protein identifiers

Apolipoprotein L3 — O95236 (reviewed: O95236)

Alternative names: Apolipoprotein L-III, TNF-inducible protein CG12-1

All UniProt accessions (13): O95236, A0A8Q3SHV3, A0A8Q3SHV8, A0A8Q3SHW2, A0A8Q3SI17, F2Z2M3, H0YCT0, H0YD32, H0YDH5, H0YDW3, H0YEQ0, H7BYQ5, H7BZT0

UniProt curated annotations — full annotation on UniProt →

Function. May affect the movement of lipids in the cytoplasm or allow the binding of lipids to organelles.

Subcellular location. Cytoplasm.

Tissue specificity. Widely expressed; the highest levels are in prostate, lung and placenta; also detected in kidney, bone marrow, spleen, thymus, spinal cord, adrenal gland, salivary gland, trachea and mammary gland; levels are low in brain, heart, fetal liver, pancreas and testis.

Induction. In vitro, is responsive to TNF.

Similarity. Belongs to the apolipoprotein L family.

Isoforms (3)

UniProt ID	Names	Canonical?
O95236-1	1	yes
O95236-2	2
O95236-3	3

RefSeq proteins (28): NP_001380516, NP_001380517, NP_001380518, NP_001380519, NP_001380520, NP_001380521, NP_001380522, NP_001380524, NP_001380525, NP_001380526, NP_001380527, NP_001380528, NP_001380529, NP_001380530, NP_001380531, NP_001380532, NP_001380533, NP_001380534, NP_001380535, NP_001380536, NP_001380537, NP_001380538, NP_055164, NP_085147, NP_663614, NP_663615, NP_663616, NP_663617 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008405	ApoL	Family

Pfam: PF05461

UniProt features (5 total): splice variant 2, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95236-F1	60.87	0.07

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 134 (showing top): GOBP_INFLAMMATORY_RESPONSE, GOBP_LIPOPROTEIN_METABOLIC_PROCESS, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, MODULE_128, WIELAND_UP_BY_HBV_INFECTION, ROZANOV_MMP14_TARGETS_UP, MODULE_171, VANHARANTA_UTERINE_FIBROID_DN, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_POSITIVE_REGULATION_OF_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_LIPID_LOCALIZATION, SANA_TNF_SIGNALING_UP, GOMF_LIPID_TRANSPORTER_ACTIVITY, BOQUEST_STEM_CELL_CULTURED_VS_FRESH_UP, WEST_ADRENOCORTICAL_CARCINOMA_VS_ADENOMA_DN

GO Biological Process (4): inflammatory response (GO:0006954), lipoprotein metabolic process (GO:0042157), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), lipid transport (GO:0006869)

GO Molecular Function (3): lipid carrier activity (GO:0005319), lipid binding (GO:0008289), protein binding (GO:0005515)

GO Cellular Component (3): extracellular region (GO:0005576), cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
binding	2
defense response	1
protein metabolic process	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
transport	1
lipid localization	1
molecular carrier activity	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

614 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
APOL3	OR5H6	Q8NGV6	400
APOL3	HMGXB3	Q12766	370
APOL3	CZIB	Q9NWV4	339
APOL3	SNN	O75324	316
APOL3	TPRKB	Q9Y3C4	305
APOL3	SDCCAG8	Q86SQ7	278
APOL3	AJM1	C9J069	256
APOL3	PCDHB6	Q9Y5E3	254
APOL3	NME6	O75414	252
APOL3	PCTP	Q9UKL6	230
APOL3	ENOX1	Q8TC92	229
APOL3	LAGE3	Q14657	226
APOL3	PLRG1	O43660	222
APOL3	BPNT2	Q9NX62	212
APOL3	MYADM	Q96S97	206

IntAct

6 interactions, top by confidence:

A	B	Type	Score
APOL3	LDHA	psi-mi:“MI:0915”(physical association)	0.400
	APOL3	psi-mi:“MI:0915”(physical association)	0.370
APOL3	purCD	psi-mi:“MI:0915”(physical association)	0.000
APOL3	dnaG	psi-mi:“MI:0915”(physical association)	0.000
	APOL3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (37): APOL3 (Protein-RNA), APOL3 (Two-hybrid), APOL3 (Two-hybrid), APOL3 (Two-hybrid), APOL3 (Two-hybrid), APOL3 (Two-hybrid), APOL3 (Two-hybrid), APOL3 (Two-hybrid), APOL3 (Two-hybrid), APOL3 (Two-hybrid), APOL3 (Two-hybrid), APOL3 (Two-hybrid), SLC16A2 (Two-hybrid), FATE1 (Two-hybrid), MFSD6 (Two-hybrid)

ESM2 similar proteins: A0A140LIF8, A0JN92, A7UHZ5, O08602, O08603, O08604, O14791, O15482, O77812, O95236, P01574, P01575, P01576, P01577, P01578, P05012, P59045, P70499, Q2KHK6, Q3B7D9, Q3TR54, Q3UQS2, Q56XQ0, Q5NCI0, Q5PPP4, Q5RFJ8, Q60766, Q6AYC2, Q6XZW6, Q6ZSC3, Q7TPX8, Q80ZF2, Q810Y8, Q86WN2, Q8BVM9, Q8CB12, Q8CCN1, Q8TCY9, Q99388, Q99J64

Diamond homologs: O14791, O95236, Q9BPW4, Q9BQE5, Q9BWW8, Q9BWW9, Q96LR9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	66
Likely benign	9
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

568 predictions. Top by Δscore:

Variant	Effect	Δscore
22:36142054:CATCC:C	acceptor_gain	1.0000
22:36142056:TCC:T	acceptor_gain	1.0000
22:36142057:CC:C	acceptor_gain	1.0000
22:36142057:CCC:C	acceptor_gain	1.0000
22:36142058:CC:C	acceptor_gain	1.0000
22:36142059:C:CC	acceptor_gain	1.0000
22:36142065:CAA:C	acceptor_gain	1.0000
22:36145599:TC:T	acceptor_loss	1.0000
22:36145600:CTA:C	acceptor_gain	1.0000
22:36145601:T:C	acceptor_loss	1.0000
22:36145603:C:CC	acceptor_gain	1.0000
22:36145604:T:C	acceptor_gain	1.0000
22:36145604:T:TC	acceptor_gain	1.0000
22:36160667:A:AC	donor_gain	1.0000
22:36160668:C:CC	donor_gain	1.0000
22:36142056:TCCC:T	acceptor_loss	0.9900
22:36142061:G:C	acceptor_gain	0.9900
22:36142064:CCAA:C	acceptor_gain	0.9900
22:36142065:C:T	acceptor_gain	0.9900
22:36142066:A:T	acceptor_gain	0.9900
22:36142067:A:AC	acceptor_gain	0.9900
22:36142067:A:C	acceptor_gain	0.9900
22:36145467:GGTTA:G	donor_loss	0.9900
22:36145468:GTTA:G	donor_loss	0.9900
22:36145469:TTA:T	donor_loss	0.9900
22:36145470:TA:T	donor_loss	0.9900
22:36145471:A:T	donor_loss	0.9900
22:36145472:C:CT	donor_loss	0.9900
22:36145598:TT:T	acceptor_gain	0.9900
22:36145601:TA:T	acceptor_gain	0.9900

AlphaMissense

2127 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:36141761:A:C	S216R	0.986
22:36141761:A:T	S216R	0.986
22:36141763:T:G	S216R	0.986
22:36141941:A:C	F156L	0.978
22:36141941:A:T	F156L	0.978
22:36141943:A:G	F156L	0.978
22:36145479:A:G	L115S	0.976
22:36145505:C:A	W106C	0.976
22:36145505:C:G	W106C	0.976
22:36141819:G:T	A197D	0.971
22:36141321:A:G	L363S	0.963
22:36145507:A:G	W106R	0.963
22:36145507:A:T	W106R	0.963
22:36141274:C:G	A379P	0.962
22:36141718:C:G	A231P	0.960
22:36141331:A:G	S360P	0.958
22:36141840:A:T	V190E	0.958
22:36145497:A:G	F109S	0.958
22:36145486:C:G	A113P	0.957
22:36141820:C:G	A197P	0.955
22:36141889:C:G	A174P	0.955
22:36141724:C:G	A229P	0.954
22:36141723:G:T	A229E	0.952
22:36145586:A:C	F79L	0.952
22:36145586:A:T	F79L	0.952
22:36145588:A:G	F79L	0.952
22:36141655:C:G	A252P	0.949
22:36145506:C:G	W106S	0.949
22:36141252:A:G	L386P	0.947
22:36141822:G:T	A196D	0.947

dbSNP variants (sampled 300 via entrez): RS1000076320 (22:36164918 G>A), RS1000123871 (22:36164506 T>A), RS1000168046 (22:36144873 C>A,T), RS1000260794 (22:36159238 A>C), RS1000376892 (22:36148534 A>C), RS1000438566 (22:36154898 C>A,G,T), RS1000472611 (22:36156115 T>A), RS1000507300 (22:36141022 T>C), RS1000606616 (22:36154540 T>C), RS1000735623 (22:36161003 G>C,T), RS1001032054 (22:36158257 G>A), RS1001074413 (22:36140017 A>G), RS1001076386 (22:36163472 G>A), RS1001117359 (22:36143507 A>C,T), RS1001302828 (22:36163915 C>T)

Disease associations

OMIM: gene MIM:607253 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST002006_7	Adverse response to chemotherapy (neutropenia/leucopenia) (paclitaxel + carboplatin)	8.000000e-06
GCST008058_38	Estimated glomerular filtration rate	1.000000e-10
GCST008059_233	Estimated glomerular filtration rate	3.000000e-10
GCST009204_18	Total intracranial volume	7.000000e-06
GCST90011898_169	Alanine aminotransferase levels	6.000000e-34
GCST90011899_94	Aspartate aminotransferase levels	8.000000e-14
GCST90011900_18	Serum alkaline phosphatase levels	9.000000e-15
GCST90013405_47	Liver enzyme levels (alanine transaminase)	7.000000e-60
GCST90013406_10	Liver enzyme levels (alkaline phosphatase)	1.000000e-25
GCST90013663_47	Alanine aminotransferase levels	4.000000e-57
GCST90013664_23	Aspartate aminotransferase levels	2.000000e-23

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004886	intracranial volume measurement
EFO:0004736	aspartate aminotransferase measurement
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

52 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects cotreatment, decreases expression, increases abundance, affects expression	3
Ozone	affects expression, affects cotreatment, decreases expression, increases abundance	3
bisphenol A	affects cotreatment, increases methylation, increases expression	2
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	2
(+)-JQ1 compound	decreases expression	2
Acetaminophen	decreases expression, increases expression	2
Acrolein	affects cotreatment, decreases expression, increases abundance	2
Benzo(a)pyrene	affects methylation, increases expression	2
Nickel	increases expression	2
Aflatoxin B1	decreases expression, decreases methylation, increases expression	2
aristolochic acid I	increases expression	1
OTX015	decreases expression	1
mivebresib	decreases expression	1
sotorasib	affects cotreatment, increases expression	1
Asian ginseng	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	decreases expression, increases abundance, affects cotreatment	1
sodium arsenite	decreases expression	1
CGP 52608	affects binding, increases reaction	1
corosolic acid	decreases expression	1
nutlin 3	affects cotreatment, increases expression	1
trametinib	affects cotreatment, increases expression	1
NVP-BKM120	affects cotreatment, increases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	increases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Arsenic	affects methylation	1
Vehicle Emissions	decreases methylation	1
Carcinogens	decreases expression	1

Clinical trials (associated diseases)

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