APOL2

Summary

APOL2 (apolipoprotein L2, HGNC:619) is a protein-coding gene on chromosome 22q12.3, encoding Apolipoprotein L2 (Q9BQE5). 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. The encoded protein is found in the cytoplasm, where it may affect the movement of lipids or allow the binding of lipids to organelles. Two transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 23780 — RefSeq curated summary.

At a glance

• Gene–disease (curated): schizophrenia (No Known Disease Relationship, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 97 total
• GTEx eGene: eQTL in 31 tissues, sQTL in 38 (q < 0.05)
• Phenotypes (HPO): 7
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.70 (unconstrained)
• MANE Select transcript: NM_030882
• Notable: 97 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:619
Approved symbol	APOL2
Name	apolipoprotein L2
Location	22q12.3
Locus type	gene with protein product
Status	Approved
Aliases	APOL-II
Ensembl gene	ENSG00000128335
Ensembl biotype	protein_coding
OMIM	607252
Entrez	23780

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 14 protein_coding, 4 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

MANE Select: ENST00000358502

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 1, TSL 3: 2, TSL 4: 4

ENST00000358502, ENST00000249066, ENST00000451256, ENST00000454728, ENST00000473549, ENST00000476579, ENST00000484830, ENST00000489186, ENST00000529194, ENST00000866480, ENST00000866481, ENST00000866482, ENST00000866483, ENST00000946286, ENST00000946287, ENST00000946288, ENST00001008347, ENST00001009763, ENST00001109602

RefSeq mRNA: 2 — MANE Select: NM_030882 NM_030882, NM_145637

CCDS: CCDS43014

Canonical transcript exons

ENST00000358502 — 5 exons

Exon	Start	End
ENSE00001773877	36231340	36231466
ENSE00002189250	36239441	36239527
ENSE00003524504	36233153	36233241
ENSE00003524514	36233402	36233455
ENSE00003712559	36226209	36228280

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 99.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.6669 / max 685.6169, expressed in 1788 samples.

Highest expression (Bgee): tendon of biceps brachii, granulocyte, apex of heart, gall bladder, adenohypophysis.

Genetic regulation across tissues (GTEx eQTL / sQTL)

APOL2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 31 tissues and its splicing (sQTL) in 38 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 69 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Brain Cerebellar Hemisphere	eqtl	4.0e-39	-0.72	22:36239710:G:A
Brain Cerebellum	eqtl	1.0e-35	-0.86	22:36239710:G:A
Brain Frontal Cortex BA9	eqtl	2.4e-34	-0.47	22:36239710:G:A
Brain Cortex	eqtl	7.4e-29	-0.46	22:36239710:G:A
Skin Sun Exposed Lower leg	sqtl	6.4e-25	+0.58	22:36236979:C:T
Nerve Tibial	sqtl	5.5e-24	+0.61	22:36236979:C:T
Brain Anterior cingulate cortex BA24	eqtl	8.7e-23	-0.47	22:36239710:G:A
Adipose Subcutaneous	sqtl	5.4e-19	+0.69	22:36236618:G:A
Adipose Visceral Omentum	sqtl	2.8e-17	+0.62	22:36236618:G:A
Lung	sqtl	3.5e-17	+0.53	22:36236618:G:A
Brain Hypothalamus	eqtl	6.2e-16	-0.40	22:36239710:G:A
Whole Blood	sqtl	1.1e-14	+0.64	22:36236597:T:G
Cells Cultured fibroblasts	sqtl	1.6e-14	-0.99	22:36225204:C:T
Cells EBV-transformed lymphocytes	sqtl	8.6e-14	-0.82	22:36236618:G:A
Breast Mammary Tissue	sqtl	1.2e-12	+0.68	22:36236618:G:A
Thyroid	sqtl	6.6e-12	+0.60	22:36236618:G:A
Spleen	sqtl	3.5e-11	-0.78	22:36232947:C:T
Brain Hippocampus	eqtl	9.4e-11	-0.33	22:36239710:G:A
Artery Tibial	sqtl	2.2e-10	+0.64	22:36236618:G:A
Skin Not Sun Exposed Suprapubic	sqtl	1.1e-09	+0.47	22:36236979:C:T

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
193875	18.1791	1683
193876	5.1568	1616
193877	0.3310	128

Top tissues by expression

showing 100 of 290 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	99.57	gold quality
granulocyte	CL:0000094	96.69	gold quality
apex of heart	UBERON:0002098	95.67	gold quality
gall bladder	UBERON:0002110	95.50	gold quality
adenohypophysis	UBERON:0002196	94.72	gold quality
medial globus pallidus	UBERON:0002477	94.70	gold quality
blood	UBERON:0000178	94.34	gold quality
cerebellar cortex	UBERON:0002129	94.32	gold quality
cerebellar hemisphere	UBERON:0002245	94.32	gold quality
monocyte	CL:0000576	94.22	gold quality
right frontal lobe	UBERON:0002810	94.14	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.07	gold quality
tibial nerve	UBERON:0001323	93.82	gold quality
pituitary gland	UBERON:0000007	93.76	gold quality
body of uterus	UBERON:0009853	93.74	gold quality
leukocyte	CL:0000738	93.58	gold quality
cerebellum	UBERON:0002037	93.58	gold quality
smooth muscle tissue	UBERON:0001135	93.57	gold quality
upper lobe of left lung	UBERON:0008952	93.54	gold quality
lymph node	UBERON:0000029	93.52	gold quality
right lobe of liver	UBERON:0001114	93.51	gold quality
mononuclear cell	CL:0000842	93.45	gold quality
spleen	UBERON:0002106	93.34	gold quality
omental fat pad	UBERON:0010414	93.33	gold quality
peritoneum	UBERON:0002358	93.32	gold quality
vena cava	UBERON:0004087	93.19	gold quality
globus pallidus	UBERON:0001875	93.04	gold quality
pericardium	UBERON:0002407	93.00	gold quality
left uterine tube	UBERON:0001303	92.91	gold quality
cingulate cortex	UBERON:0003027	92.85	gold quality
anterior cingulate cortex	UBERON:0009835	92.84	gold quality
adipose tissue of abdominal region	UBERON:0007808	92.79	gold quality
islet of Langerhans	UBERON:0000006	92.78	gold quality
metanephros cortex	UBERON:0010533	92.76	gold quality
heart left ventricle	UBERON:0002084	92.70	gold quality
cardiac ventricle	UBERON:0002082	92.61	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.50	gold quality
vagina	UBERON:0000996	92.49	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.36	gold quality
ectocervix	UBERON:0012249	92.35	gold quality
mucosa of stomach	UBERON:0001199	92.32	gold quality
upper lobe of lung	UBERON:0008948	92.26	gold quality
cerebellar vermis	UBERON:0004720	92.22	gold quality
endocervix	UBERON:0000458	92.21	gold quality
parotid gland	UBERON:0001831	92.21	gold quality
caecum	UBERON:0001153	92.20	gold quality
prostate gland	UBERON:0002367	92.09	gold quality
vermiform appendix	UBERON:0001154	92.02	gold quality
type B pancreatic cell	CL:0000169	91.95	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	91.93	gold quality
rectum	UBERON:0001052	91.89	gold quality
minor salivary gland	UBERON:0001830	91.87	gold quality
olfactory bulb	UBERON:0002264	91.86	gold quality
small intestine	UBERON:0002108	91.79	gold quality
substantia nigra pars compacta	UBERON:0001965	91.78	gold quality
tendon	UBERON:0000043	91.75	gold quality
saliva-secreting gland	UBERON:0001044	91.68	gold quality
nasal cavity epithelium	UBERON:0005384	91.68	gold quality
right coronary artery	UBERON:0001625	91.57	gold quality
myometrium	UBERON:0001296	91.33	gold quality
liver	UBERON:0002107	91.31	gold quality
subcutaneous adipose tissue	UBERON:0002190	91.31	gold quality
heart	UBERON:0000948	91.20	gold quality
right uterine tube	UBERON:0001302	91.11	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.11	gold quality
lower esophagus	UBERON:0013473	91.10	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.09	gold quality
right atrium auricular region	UBERON:0006631	91.03	gold quality
descending thoracic aorta	UBERON:0002345	91.01	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	90.96	gold quality
fallopian tube	UBERON:0003889	90.88	gold quality
oviduct epithelium	UBERON:0004804	90.75	gold quality
frontal cortex	UBERON:0001870	90.74	gold quality
amygdala	UBERON:0001876	90.73	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.73	gold quality
adipose tissue	UBERON:0001013	90.69	gold quality
uterus	UBERON:0000995	90.63	gold quality
cardiac atrium	UBERON:0002081	90.61	gold quality
neocortex	UBERON:0001950	90.56	gold quality
connective tissue	UBERON:0002384	90.52	gold quality
mouth mucosa	UBERON:0003729	90.47	gold quality
primary visual cortex	UBERON:0002436	90.45	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.38	gold quality
coronary artery	UBERON:0001621	90.37	gold quality
right lung	UBERON:0002167	90.35	gold quality
inferior olivary complex	UBERON:0002127	90.32	gold quality
duodenum	UBERON:0002114	90.30	gold quality
left coronary artery	UBERON:0001626	90.27	gold quality
body of stomach	UBERON:0001161	90.20	gold quality
substantia nigra	UBERON:0002038	90.19	gold quality
transverse colon	UBERON:0001157	90.18	gold quality
prefrontal cortex	UBERON:0000451	90.15	gold quality
right adrenal gland	UBERON:0001233	90.13	gold quality
left adrenal gland	UBERON:0001234	90.12	gold quality
pons	UBERON:0000988	90.03	gold quality
thoracic aorta	UBERON:0001515	90.02	gold quality
ascending aorta	UBERON:0001496	89.98	gold quality
midbrain	UBERON:0001891	89.95	gold quality
buccal mucosa cell	CL:0002336	89.92	gold quality
substantia nigra pars reticulata	UBERON:0001966	89.88	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-7052	yes	815.28
E-GEOD-81608	yes	16.61
E-ANND-3	yes	11.21
E-MTAB-5061	yes	8.88
E-MTAB-7303	no	281.80
E-MTAB-7249	no	78.58

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 63 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Medulla oblongata	tissue	75.9
Pons	tissue	75.8
Locus coeruleus	tissue	65.1
Liver	tissue	61.1	medium
Hypothalamus	tissue	57.4
Urinary bladder	tissue	55.5	high
Cerebral cortex	tissue	55.4	medium
Spinal cord	tissue	55.4
Postcentral gyrus	tissue	55.4
Midbrain	tissue	55.2
Substantia nigra	tissue	55.2
Thalamus	tissue	48.2
Pituitary gland	tissue	47.8
Occipital cortex	tissue	46.1
Cerebellum	tissue	44.2	high
Amygdala	tissue	42.6
Spleen	tissue	42.6	medium
Retrosplenial cortex	tissue	41.7
Basal ganglia	tissue	41.5	medium
Appendix	tissue	41.1	medium
Choroid plexus	tissue	39.9
Lymph node	tissue	39.7	medium
Gallbladder	tissue	39.5	medium
Duodenum	tissue	39.3	medium
Hippocampal formation	tissue	37.4
Stomach 1	tissue	36.1	medium
Hippocampus	tissue	34.7	high
Smooth muscle	tissue	33.5	medium
Lung	tissue	33.3	high
Endometrium 1	tissue	31.0	medium
Small intestine	tissue	30.4	medium
Adipose tissue	tissue	29.2	not detected
Tonsil	tissue	28.4	high
Thymus	tissue	27.6
Heart muscle	tissue	27.1	low
Seminal vesicle	tissue	26.6	medium
Vagina	tissue	25.3	not detected
Rectum	tissue	24.8	low
Salivary gland	tissue	23.6	low
Putamen	tissue	23.6
Cervix	tissue	23.5	high
Skeletal muscle	tissue	22.3	not detected
Prostate	tissue	21.2	low
Adrenal gland	tissue	21.0	high
Placenta	tissue	20.9	high
Colon	tissue	20.6	low
Fallopian tube	tissue	20.4	high
Breast	tissue	19.1	low
Parathyroid gland	tissue	18.5	low
Nucleus accumbens	tissue	18.5
Ovary	tissue	18.4	medium
Tongue	tissue	17.1
Epididymis	tissue	16.8	medium
Kidney	tissue	16.8	high
Skin 1	tissue	15.2	not detected
Pancreas	tissue	14.5	high
Esophagus	tissue	14.1	not detected
Bone marrow	tissue	12.3	high
Thyroid gland	tissue	12.0	medium
Retina	tissue	11.3

Brain sub-regions (HPA Brain Atlas): detected in 188; highest nTPM — Peritrigeminal nucleus (75.9), Pontine nuclei (75.8), Nucleus raphe magnus (74.8), Nuclei of the trapezoid body (72.0), Spinal trigeminal nucleus, oral (70.5).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting APOL2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 36 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-20A-3P	99.44	69.10	1575
HSA-MIR-548AV-3P	99.43	68.50	1721
HSA-MIR-584-3P	99.35	67.69	1082
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-3199	99.17	65.19	696
HSA-MIR-8052	99.17	65.01	719
HSA-MIR-6749-3P	99.00	65.73	1443
HSA-MIR-1207-3P	98.99	66.22	1532
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-6737-3P	98.95	68.56	1577
HSA-MIR-7157-3P	98.95	68.70	1582
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-4290	98.51	65.17	907
HSA-MIR-6764-3P	98.44	67.64	1153
HSA-MIR-6824-3P	98.44	67.62	1154
HSA-MIR-326	98.25	66.44	1565
HSA-MIR-4518	98.12	66.82	1030
HSA-MIR-1266-5P	97.71	66.92	1052
HSA-MIR-4288	97.11	67.23	1636

Functional genomics

gnomAD constraint: pLI 0.00111, LOEUF 1.7, missense Z -0.589 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000358502 — one region, missense o/e 1.13.

Literature-anchored findings (GeneRIF, showing 6)

• APOL2 has been found only in humans and African green monkeys (PMID:11944986)
• An association of APOL1, 2 and 4 with schizophrenia was establised. (PMID:18632255)
• Results reveal a novel function for ApoL2 in conferring anti-apoptotic ability of human bronchial epithelium to the cytotoxic effects of IFN-gamma, in maintaining airway epithelial layer integrity. (PMID:20665705)
• Apolipoprotein L2 contains a BH3-like domain but it does not behave as a BH3-only protein. (PMID:24901046)
• Epigenetic aging is accelerated in alcohol use disorder and regulated by genetic variation in APOL2. (PMID:31466081)
• Structures of the ApoL1 and ApoL2 N-terminal domains reveal a non-classical four-helix bundle motif. (PMID:34316015)

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), APOL3 (ENSG00000128284), APOL5 (ENSG00000128313), 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
APOL4	protein-coding	80832
MYH9-DT	ncRNA	105377199
MYH9	protein-coding	4627
APOL1	protein-coding	8542
MIR6819	ncRNA	102465491

Protein

Protein identifiers

Apolipoprotein L2 — Q9BQE5 (reviewed: Q9BQE5)

Alternative names: Apolipoprotein L-II

All UniProt accessions (4): B0QYK8, E9PM95, J3KQL8, Q9BQE5

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 found in lung, thymus, pancreas, placenta, adult brain and prostate; also detected in spleen, liver, kidney, colon, small intestine, uterus, spinal cord, adrenal gland, salivary gland, trachea, mammary gland, skeletal muscle, testis and fetal brain and liver.

Similarity. Belongs to the apolipoprotein L family.

RefSeq proteins (2): NP_112092, NP_663612 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008405	ApoL	Family

Pfam: PF05461

UniProt features (10 total): helix 4, modified residue 2, sequence variant 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
7LF8	Fab 6D12 bound to ApoL2 NTD	X-RAY DIFFRACTION	2.15

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BQE5-F1	54.04	0.00

Antibody-complex structures (SAbDab)

1 antibodies co-crystallized with this protein: 7LF8

Human Protein Atlas

Protein class: Predicted membrane proteins, Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Mutated cancer genes, Human disease related genes, Mental and behavioural disorders

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH supported

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 (2)

Type	Positions
N-acetylmethionine	1
Phosphoserine	250

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: 148 (showing top): GOBP_INFLAMMATORY_RESPONSE, GOBP_LIPOPROTEIN_METABOLIC_PROCESS, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_LIPID_METABOLIC_PROCESS, GOBP_MULTI_MULTICELLULAR_ORGANISM_PROCESS, GOBP_MATERNAL_PROCESS_INVOLVED_IN_FEMALE_PREGNANCY, GOMF_SIGNALING_RECEPTOR_BINDING, GOBP_LIPID_LOCALIZATION, GOBP_STEROID_METABOLIC_PROCESS, GOBP_ACUTE_PHASE_RESPONSE, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_DN, GOBP_ALCOHOL_METABOLIC_PROCESS, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOCC_ORGANELLE_SUBCOMPARTMENT, GOMF_PROTEIN_LIPID_COMPLEX_BINDING

GO Biological Process (6): lipid metabolic process (GO:0006629), lipid transport (GO:0006869), acute-phase response (GO:0006953), cholesterol metabolic process (GO:0008203), lipoprotein metabolic process (GO:0042157), maternal process involved in female pregnancy (GO:0060135)

GO Molecular Function (4): signaling receptor binding (GO:0005102), high-density lipoprotein particle binding (GO:0008035), lipid binding (GO:0008289), protein binding (GO:0005515)

GO Cellular Component (4): extracellular region (GO:0005576), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), cytoplasm (GO:0005737)

GO top-level categories

17 GO namespaces:

Category	Terms
cellular anatomical structure	3
binding	2
primary metabolic process	1
transport	1
lipid localization	1
acute inflammatory response	1
sterol metabolic process	1
secondary alcohol metabolic process	1
protein metabolic process	1
female pregnancy	1
multicellular organismal reproductive process	1
protein binding	1
lipoprotein particle binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
intracellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 14 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 732 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
APOL2	COMT	P21964	674
APOL2	CHRM4	P08173	505
APOL2	SNRPB2	P08579	494
APOL2	PRODH	O43272	494
APOL2	CGB5	P01233	491
APOL2	PRODH	O43272	487
APOL2	PLAAT2	Q9NWW9	429
APOL2	CGB5	P01233	425
APOL2	PDE4B	Q07343	424
APOL2	PXT1	Q8NFP0	416
APOL2	APOO	Q9BUR5	400
APOL2	NXPE3	Q969Y0	388
APOL2	P2RY11	Q96G91	384
APOL2	SYN2	Q92777	360
APOL2	ARHGAP39	Q9C0H5	359

IntAct

Human interaction partners of APOL2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 35 partners by confidence:

Partner	Interaction type	MIscore	Records
AIG1	physical association	0.560	3
APOC4	physical association	0.560	3
BSND	physical association	0.560	3
CISD2	physical association	0.560	3
CYBC1	physical association	0.560	3
EBAG9	physical association	0.560	3
EMP1	physical association	0.560	3
ERGIC3	physical association	0.560	3
FAM209A	physical association	0.560	3
GET1	physical association	0.560	3
GJB5	physical association	0.560	3
ITGB2	physical association	0.560	3
KCNA1	physical association	0.560	3
MARCHF3	physical association	0.560	3
MFF	physical association	0.560	3
MGST3	physical association	0.560	3
PANX1	physical association	0.560	3
SFXN5	physical association	0.560	3
SIT1	physical association	0.560	3
SLC18A1	physical association	0.560	3
SLC26A6	physical association	0.560	3
STX1A	physical association	0.560	3
STX2	physical association	0.560	3
TMED8	physical association	0.560	3
TMEM139	physical association	0.560	3
TMEM179B	physical association	0.560	3
TMEM45B	physical association	0.560	3
TMEM52B	physical association	0.560	3
TMEM60	physical association	0.560	3
USE1	physical association	0.560	3

BioGRID (149 interactions; top human partners by supporting records): APBB2 (Affinity Capture-MS; 3 records), PSG9 (Affinity Capture-MS; 3 records), UBB (Affinity Capture-MS; 3 records), BPNT1 (Affinity Capture-MS; 2 records), CHRNA3 (Affinity Capture-MS; 2 records), CHRND (Affinity Capture-MS; 2 records), EID3 (Affinity Capture-MS; 2 records), ERAP1 (Affinity Capture-MS; 2 records), GBP5 (Affinity Capture-MS; 2 records), GNAZ (Affinity Capture-MS; 2 records), HTR3A (Affinity Capture-MS; 2 records), SEC61B (Proximity Label-MS; 2 records), SOD1 (Affinity Capture-MS; 2 records), TMEM30A (Affinity Capture-MS; 2 records), AIG1 (Two-hybrid)

Disease & clinical

Genetic variants

Variant evidence for APOL2: 97 ClinVar records (0 pathogenic / likely pathogenic); 2 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	76
Likely benign	8
Benign	1

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 44 predictions of 299):

Position(s)	Effect	Δscore	Sites
22:36231338–36231339	donor_loss	1.0000	4
22:36228281–36228282	acceptor_loss	0.9900	6
22:36231467–36231468	acceptor_loss	0.9900	6
22:36231471	acceptor_gain	0.9900
22:36233151–36233152	donor_loss	0.9900	5
22:36233242–36233243	acceptor_gain	0.9900	2
22:36233242–36233243	acceptor_loss	0.9900	4
22:36233400–36233401	donor_loss	0.9900	5
22:36233456–36233457	acceptor_loss	0.9900	6
22:36239439–36239440	donor_loss	0.9900	5

AlphaMissense

278 missense substitutions predicted likely pathogenic (of 2,199 scored), across 127 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
D287	8	0.721	0.813
W35	7	0.914	0.967
F85	7	0.849	0.973
F81	6	0.861	0.934
H110	6	0.692	0.792
F38	5	0.871	0.901
S145	5	0.774	0.904
F16	4	0.830	0.831
F198	4	0.793	0.867
K89	4	0.792	0.880
G221	4	0.694	0.799
G156	4	0.642	0.692
L44	3	0.809	0.885
S127	3	0.802	0.876
L324	3	0.796	0.896
L321	3	0.793	0.904
L28	3	0.787	0.886
L56	3	0.778	0.864
L52	3	0.761	0.870
L130	3	0.751	0.797

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

1 prognostic cancer types:

Cancer	Prognostic	p-value
Lung Adenocarcinoma (TCGA)	unfavorable	0.000158

Disease associations

OMIM: gene MIM:607252 | disease phenotypes:

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
schizophrenia	No Known Disease Relationship	Autosomal dominant

Mondo (1): schizophrenia (MONDO:0005090)

HPO phenotypes

7 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000738	Hallucinations
HP:0000746	Delusion
HP:0002353	EEG abnormality
HP:0007086	Social and occupational deterioration
HP:0100753	Schizophrenia
HP:0410291	Negativism

GWAS associations

2 associations:

Study	Trait	p-value
GCST008748_1	Epigenetic age acceleration in alcohol use disorder	5e-8
GCST008748_7	Epigenetic age acceleration in alcohol use disorder	4e-7

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0000473	epigenetic status
EFO:0022597	aging

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
manganese chloride	increases expression, affects cotreatment, increases abundance	2
Manganese	increases expression, affects cotreatment, increases abundance	2
Nickel	increases expression	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
trichostatin A	decreases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	increases expression	1
nickel chloride	increases expression	1
perfluorooctanoic acid	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
benazol P	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
nutlin 3	affects cotreatment, increases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
jinfukang	increases expression, affects cotreatment	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Leflunomide	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Cannabinoids	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1EJ	Abcam A-549 APOL2 KO 2	Cancer cell line	Male
CVCL_B2M2	Abcam A-549 APOL2 KO 1	Cancer cell line	Male

Clinical trials (associated diseases)

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

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT00000374	Phase 4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	Phase 4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	Phase 4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	Phase 4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	Phase 4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	Phase 4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	Phase 4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	Phase 4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	Phase 4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	Phase 4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	Phase 4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	Phase 4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	Phase 4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	Phase 4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	Phase 4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	Phase 4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	Phase 4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	Phase 4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	Phase 4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	Phase 4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	Phase 4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	Phase 4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	Phase 4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	Phase 4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	Phase 4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	Phase 4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	Phase 4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	Phase 4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	Phase 4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	Phase 4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	Phase 4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	Phase 4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	Phase 4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	Phase 4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	Phase 4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	Phase 4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	Phase 4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	Phase 4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	Phase 4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	Phase 4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety
NCT00177580	Phase 4	COMPLETED	Improving Symptoms of Schizophrenia and Schizoaffective Disorder by Supplementing Medications With Pravastatin
NCT00182442	Phase 4	COMPLETED	Cognition, Functioning and Quality of Life
NCT00182494	Phase 4	UNKNOWN	Diabetes Prevention Program in Schizophrenia [DPPS]
NCT00183625	Phase 4	COMPLETED	Supported Employment and Skills Training in Conjunction With Pharmacotherapy in Schizophrenia Patients
NCT00186771	Phase 4	UNKNOWN	Magnetic Stimulation as a Treatment for Auditory Hallucinations in Schizophrenia
NCT00190749	Phase 4	COMPLETED	Safety Study of Olanzapine and a Comparator in Patients With Schizophrenia and Schizoaffective Disorder
NCT00191555	Phase 4	COMPLETED	Efficacy Study of Switching Stabilized Schizophrenic Patients From Conventional to Atypical Antipsychotic Treatment
NCT00194025	Phase 4	COMPLETED	Valproate in Late Life Schizophrenia
NCT00199940	Phase 4	COMPLETED	Safety And Efficacy Study Of Ziprasidone In Pediatric Psychotic Illness
NCT00202306	Phase 4	COMPLETED	Indicated Prevention of Psychotic Disorders With Low-dose Lithium
NCT00203788	Phase 4	COMPLETED	Improving Work Outcome in People With Recent-onset Schizophrenia
NCT00204061	Phase 4	COMPLETED	Early Pharmacological and Psychological Intervention for Late Prodromal States of Psychosis
NCT00205660	Phase 4	COMPLETED	Changes in Adiposity, Metabolic Measures From Atypicals to Aripiprazole
NCT00206102	Phase 4	COMPLETED	A Study of the Cataractogenic Potential of Seroquel and Risperdal in the Treatment of Participants With Schizophrenia or Schizoaffective Disorder
NCT00208143	Phase 4	COMPLETED	Seroquel Therapy for Substance Use Disorders Comorbid With Schizophrenia
NCT00208169	Phase 4	COMPLETED	Abilify Therapy for Reducing Comorbid Substance Abuse
NCT00214578	Phase 4	COMPLETED	Seroquel on Glucose Metabolism
NCT00215579	Phase 4	COMPLETED	Determining the Effects of Risperdal Consta in Patients With Psychotic Disorders and Incomplete Adherence
NCT00216528	Phase 4	COMPLETED	A Study to Evaluate Symptomatic Remission in Schizophrenia With Long Acting Risperidone Microspheres
NCT00216632	Phase 4	COMPLETED	A Study of Treatment Success in Changing From Olanzapine to Long-acting Injectable Risperidone (RISPERDAL® CONSTA™)