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
• GTEx eGene: eQTL in 24 tissues, sQTL in 14 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.75 (unconstrained)
• MANE Select transcript: NM_145639
• Notable: 87 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 39 — 31 protein_coding, 4 nonsense_mediated_decay, 4 protein_coding_CDS_not_defined

MANE Select: ENST00000424878

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 8, TSL 3: 4, TSL 4: 7, TSL 5: 1

ENST00000424878, ENST00000349314, ENST00000361710, ENST00000397287, ENST00000397289, ENST00000422426, 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, ENST00001131555

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.

Highest expression (Bgee): granulocyte, monocyte, mononuclear cell, leukocyte, apex of heart.

Genetic regulation across tissues (GTEx eQTL / sQTL)

APOL3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 24 tissues and its splicing (sQTL) in 14 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 38 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Adipose Subcutaneous	sqtl	2.4e-27	+0.67	22:36149778:T:C
Thyroid	sqtl	1.9e-15	+0.51	22:36149778:T:C
Lung	sqtl	2.1e-14	+0.49	22:36149778:T:C
Nerve Tibial	sqtl	2.3e-14	+0.57	22:36149778:T:C
Skin Sun Exposed Lower leg	sqtl	9.8e-13	+0.54	22:36149778:T:C
Cells EBV-transformed lymphocytes	sqtl	5.7e-11	-0.68	22:36148681:A:G
Adipose Visceral Omentum	sqtl	6.7e-09	+0.48	22:36149778:T:C
Skin Not Sun Exposed Suprapubic	eqtl	7.5e-08	-0.20	22:36193355:T:C
Breast Mammary Tissue	sqtl	5.3e-07	-0.47	22:36149089:A:T
Esophagus Gastroesophageal Junction	eqtl	9.2e-06	-0.23	22:36141845:A:G
Esophagus Muscularis	sqtl	3.8e-05	-0.42	22:36134380:G:A
Colon Sigmoid	eqtl	8.3e-05	-0.17	22:36161502:C:T
Nerve Tibial	eqtl	1.5e-04	+0.12	22:36144735:C:T
Esophagus Muscularis	eqtl	6.8e-04	-0.15	22:36141845:A:G
Adipose Subcutaneous	eqtl	8.5e-04	-0.18	22:36141845:A:G
Spleen	sqtl	9.5e-04	-0.45	22:36134380:G:A
Artery Tibial	sqtl	1.1e-03	-0.38	22:36143756:A:G
Esophagus Gastroesophageal Junction	sqtl	1.3e-03	-0.46	22:36134380:G:A
Stomach	eqtl	2.0e-03	-0.17	22:36141845:A:G
Adipose Visceral Omentum	eqtl	3.4e-03	-0.18	22:36141845:A:G

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

showing 100 of 286 tissues 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
esophagogastric junction muscularis propria	UBERON:0035841	93.62	gold quality
lower esophagus	UBERON:0013473	93.60	gold quality
left lobe of thyroid gland	UBERON:0001120	93.53	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.24	gold quality
heart left ventricle	UBERON:0002084	93.07	gold quality
cardiac ventricle	UBERON:0002082	92.97	gold quality
thyroid gland	UBERON:0002046	92.67	gold quality
gall bladder	UBERON:0002110	92.65	gold quality
layer of synovial tissue	UBERON:0007616	92.63	gold quality
lung	UBERON:0002048	92.56	gold quality
superficial temporal artery	UBERON:0001614	92.50	gold quality
descending thoracic aorta	UBERON:0002345	92.38	gold quality
right coronary artery	UBERON:0001625	92.32	gold quality
small intestine	UBERON:0002108	92.32	gold quality
blood	UBERON:0000178	92.14	gold quality
rectum	UBERON:0001052	92.14	gold quality
skin of leg	UBERON:0001511	92.04	gold quality
heart	UBERON:0000948	91.71	gold quality
minor salivary gland	UBERON:0001830	91.59	gold quality
right atrium auricular region	UBERON:0006631	91.56	gold quality
ectocervix	UBERON:0012249	91.55	gold quality
coronary artery	UBERON:0001621	91.47	gold quality
cardiac atrium	UBERON:0002081	91.32	gold quality
left coronary artery	UBERON:0001626	91.30	gold quality
lower lobe of lung	UBERON:0008949	91.30	gold quality
bone marrow cell	CL:0002092	91.19	gold quality
endocervix	UBERON:0000458	90.80	gold quality
metanephros cortex	UBERON:0010533	90.75	gold quality
right lobe of liver	UBERON:0001114	90.66	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.62	gold quality
smooth muscle tissue	UBERON:0001135	90.54	gold quality
thoracic aorta	UBERON:0001515	90.50	gold quality
ascending aorta	UBERON:0001496	90.34	gold quality
aorta	UBERON:0000947	90.31	gold quality
tibial artery	UBERON:0007610	90.26	gold quality
popliteal artery	UBERON:0002250	90.22	gold quality
esophagus	UBERON:0001043	90.16	gold quality
skin of abdomen	UBERON:0001416	90.04	gold quality
tonsil	UBERON:0002372	90.04	gold quality
right uterine tube	UBERON:0001302	90.01	gold quality
mouth mucosa	UBERON:0003729	89.90	gold quality
fundus of stomach	UBERON:0001160	89.78	gold quality
myometrium	UBERON:0001296	89.60	gold quality
muscle of leg	UBERON:0001383	89.55	gold quality
right adrenal gland cortex	UBERON:0035827	89.52	gold quality
diaphragm	UBERON:0001103	89.38	gold quality
uterine cervix	UBERON:0000002	89.32	gold quality
zone of skin	UBERON:0000014	89.15	gold quality
gastrocnemius	UBERON:0001388	89.13	gold quality
left ventricle myocardium	UBERON:0006566	89.11	gold quality
vagina	UBERON:0000996	88.97	gold quality
thoracic mammary gland	UBERON:0005200	88.95	gold quality
heart right ventricle	UBERON:0002080	88.93	gold quality
mammary gland	UBERON:0001911	88.92	gold quality
right adrenal gland	UBERON:0001233	88.91	gold quality
urethra	UBERON:0000057	88.88	gold quality
liver	UBERON:0002107	88.77	gold quality
urinary bladder	UBERON:0001255	88.75	gold quality
mammary duct	UBERON:0001765	88.67	gold quality
adrenal cortex	UBERON:0001235	88.65	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.61	gold quality
muscle organ	UBERON:0001630	88.59	gold quality
penis	UBERON:0000989	88.58	gold quality
left adrenal gland cortex	UBERON:0035825	88.58	gold quality
saliva-secreting gland	UBERON:0001044	88.47	gold quality
saphenous vein	UBERON:0007318	88.42	gold quality
left adrenal gland	UBERON:0001234	88.39	gold quality
cervix squamous epithelium	UBERON:0006922	88.27	silver quality
pylorus	UBERON:0001166	88.26	gold quality
intestine	UBERON:0000160	88.22	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 61 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Spleen	tissue	91.5
Lymph node	tissue	75.7
Liver	tissue	67.0
Lung	tissue	59.7
Adipose tissue	tissue	54.7
Appendix	tissue	49.2
Tonsil	tissue	40.6
Breast	tissue	32.4
Tongue	tissue	32.3
Thymus	tissue	32.1
Smooth muscle	tissue	32.0
Placenta	tissue	31.1
Skeletal muscle	tissue	30.1
Heart muscle	tissue	30.0
Duodenum	tissue	29.9
Urinary bladder	tissue	27.9
Fallopian tube	tissue	27.6
Small intestine	tissue	25.9
Endometrium 1	tissue	25.8
Salivary gland	tissue	25.4
Medulla oblongata	tissue	24.9
Stomach 1	tissue	24.4
Rectum	tissue	23.5
Seminal vesicle	tissue	23.0
Thalamus	tissue	22.9
Colon	tissue	21.1
Epididymis	tissue	20.9
Bone marrow	tissue	20.8
Gallbladder	tissue	20.6
Amygdala	tissue	20.1
Pons	tissue	19.9
Ovary	tissue	19.5
Basal ganglia	tissue	19.4
Skin 1	tissue	19.2
Midbrain	tissue	19.0
Substantia nigra	tissue	19.0
Vagina	tissue	18.7
Cervix	tissue	17.9
Adrenal gland	tissue	17.4
Cerebral cortex	tissue	16.4
Prostate	tissue	16.1
Hypothalamus	tissue	15.7
Putamen	tissue	15.6
Esophagus	tissue	15.3
Spinal cord	tissue	15.0
Thyroid gland	tissue	14.6
Locus coeruleus	tissue	14.5
Kidney	tissue	14.4
Cerebellum	tissue	14.1
Hippocampus	tissue	13.8
Hippocampal formation	tissue	13.8
Retrosplenial cortex	tissue	13.1
Choroid plexus	tissue	12.6
Nucleus accumbens	tissue	11.1
Occipital cortex	tissue	9.3
Pituitary gland	tissue	8.3
Postcentral gyrus	tissue	7.2
Parathyroid gland	tissue	6.8
Testis	tissue	5.1
Pancreas	tissue	5.0

Brain sub-regions (HPA Brain Atlas): detected in 185; highest nTPM — Peritrigeminal nucleus (24.9), Area postrema (24.1), Nucleus gracilis (23.7), Posterior thalamic nucleus (22.9), Parvicellular reticular nuclei, medullary (22.3).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting APOL3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 44 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 3.68e-06, LOEUF 1.75, missense Z 0.748 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000349314 — one region, missense o/e 0.98.

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

19 orthologs

Organism	Symbol	Gene ID
mus_musculus	Apol7a	ENSMUSG00000010601
mus_musculus	Apol7c	ENSMUSG00000044309
mus_musculus	Apol10b	ENSMUSG00000050014
mus_musculus	Apol10a	ENSMUSG00000050982
mus_musculus	Apol9a	ENSMUSG00000057346
mus_musculus	Apol9b	ENSMUSG00000068246
mus_musculus	Apol7b	ENSMUSG00000068252
mus_musculus	Apol7e	ENSMUSG00000071716
mus_musculus	Apol11a	ENSMUSG00000091650
mus_musculus	Apol11b	ENSMUSG00000091694
rattus_norvegicus	Apol9a	ENSRNOG00000023410
rattus_norvegicus	Apol3l1	ENSRNOG00000042771
rattus_norvegicus	AABR07058479.1	ENSRNOG00000047414
rattus_norvegicus	Apol7bl1	ENSRNOG00000047782
rattus_norvegicus	Apol7a	ENSRNOG00000052981
rattus_norvegicus	LOC120093819	ENSRNOG00000069032
rattus_norvegicus	Apol11a	ENSRNOG00000081988
caenorhabditis_elegans		WBGENE00017219
caenorhabditis_elegans		WBGENE00017220

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

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1923011) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 3 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal dendritic cell physiology	1
abnormal dendritic cell antigen presentation	1
increased heart left ventricle size	1

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
RBFOX2	protein-coding	23543
APOL5	protein-coding	80831

Protein

Protein identifiers

Apolipoprotein L3 — O95236 (reviewed: O95236)

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

All UniProt accessions (13): A0A8Q3SHV3, A0A8Q3SHV8, A0A8Q3SHW2, A0A8Q3SI17, O95236, 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

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Function

Pathways and Gene Ontology

Reactome pathways

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

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

11 GO namespaces:

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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 10 annotations. The rest are phylogenetic / computational / electronic (IEA).

1 experimentally-supported GO terms:

GO term	NS	Evidence
membrane	CC	high-throughput assay

Protein interactions and networks

STRING

showing 15 of 422 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
APOL3	OR5H6	Q8NGV6	374
APOL3	HMGXB3	Q12766	286
APOL3	CZIB	Q9NWV4	274
APOL3	PLRG1	O43660	248
APOL3	APOL5	Q9BWW9	229
APOL3	TPRKB	Q9Y3C4	225
APOL3	SNN	O75324	225
APOL3	SDCCAG8	Q86SQ7	221
APOL3	SCARF2	Q96GP6	211
APOL3	C2CD2L	O14523	209
APOL3	NME6	O75414	206
APOL3	PCDHB6	Q9Y5E3	205
APOL3	PCTP	Q9UKL6	198
APOL3	ENOX1	Q8TC92	193
APOL3	NEK4	P51957	192

IntAct

Human interaction partners of APOL3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

1 partners by confidence:

Partner	Interaction type	MIscore	Records
LDHA	physical association	0.400	1

BioGRID (37 interactions; top human partners by supporting records): AQP6 (Two-hybrid), CYB5R3 (Two-hybrid), ELOVL4 (Two-hybrid), FAM209A (Two-hybrid), FATE1 (Two-hybrid), FXYD6-FXYD2 (Two-hybrid), GBP1 (Phenotypic Enhancement), GJA8 (Two-hybrid), GJB1 (Two-hybrid), GJB5 (Two-hybrid), GJC1 (Two-hybrid), GPR152 (Two-hybrid), GPRC5D (Two-hybrid), HAS3 (Two-hybrid), IL7R (Two-hybrid)

Disease & clinical

Genetic variants

Variant evidence for APOL3: 87 ClinVar records (0 pathogenic / likely pathogenic); 11 GWAS associations.

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

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 25 predictions of 287):

Position(s)	Effect	Δscore	Sites
22:36145600–36145601	acceptor_loss	1.0000	5
22:36145604	acceptor_gain	1.0000
22:36142059–36142060	acceptor_loss	0.9900	2
22:36142061	acceptor_gain	0.9900
22:36142065–36142067	acceptor_gain	0.9900	3
22:36145471–36145472	donor_loss	0.9900	5
22:36145601	acceptor_loss	0.9900
22:36160667–36160668	donor_loss	0.9900	5
22:36142059	acceptor_loss	0.9800
22:36145612	acceptor_gain	0.9800

AlphaMissense

466 missense substitutions predicted likely pathogenic (of 2,127 scored), across 176 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
D352	8	0.850	0.913
W106	7	0.933	0.976
F156	7	0.874	0.978
F109	7	0.843	0.958
F152	7	0.812	0.943
H181	7	0.798	0.884
C184	7	0.686	0.877
S216	6	0.896	0.986
F87	6	0.833	0.934
I186	6	0.768	0.940
G366	6	0.767	0.909
P210	6	0.757	0.866
F79	5	0.910	0.952
G223	5	0.858	0.908
Y86	5	0.808	0.877
M201	5	0.783	0.928
G292	5	0.776	0.901
R299	5	0.754	0.837
G214	5	0.725	0.826
V190	5	0.723	0.958

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Bladder Urothelial Carcinoma (TCGA)	favorable	1.38e-06
Liver Hepatocellular Carcinoma (validation)	favorable	0.000187
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.0004

Disease associations

OMIM: gene MIM:607253 | disease phenotypes:

GWAS associations

11 associations:

Study	Trait	p-value
GCST90013405_22	Liver enzyme levels (alanine transaminase)	7e-60
GCST90013663_58	Alanine aminotransferase levels	4e-57
GCST90011898_79	Alanine aminotransferase levels	6e-34
GCST90013406_10	Liver enzyme levels (alkaline phosphatase)	1e-25
GCST90013664_23	Aspartate aminotransferase levels	2e-23
GCST90011900_43	Serum alkaline phosphatase levels	9e-15
GCST90011899_101	Aspartate aminotransferase levels	8e-14
GCST008058_195	Estimated glomerular filtration rate	1e-10
GCST008059_206	Estimated glomerular filtration rate	3e-10
GCST009204_6	Total intracranial volume	7e-6
GCST002006_4	Adverse response to chemotherapy (neutropenia/leucopenia) (paclitaxel + carboplatin)	8e-6

EFO canonical traits (from GWAS)

3 canonical traits:

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 (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, increases abundance, affects expression, affects cotreatment	3
Ozone	affects cotreatment, decreases expression, increases abundance, affects expression	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	increases expression, affects methylation	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	increases reaction, affects binding	1
corosolic acid	decreases expression	1
nutlin 3	affects cotreatment, increases expression	1
trametinib	increases expression, affects cotreatment	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)

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