APOL6

Summary

APOL6 (apolipoprotein L6, HGNC:14870) is a protein-coding gene on chromosome 22q12.3, encoding Apolipoprotein L6 (Q9BWW8). 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.

Source: NCBI Gene 80830 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 82 total
• MANE Select transcript: NM_030641

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14870
Approved symbol	APOL6
Name	apolipoprotein L6
Location	22q12.3
Locus type	gene with protein product
Status	Approved
Aliases	APOL-VI, APOLVI
Ensembl gene	ENSG00000221963
Ensembl biotype	protein_coding
OMIM	607256
Entrez	80830

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000409652, ENST00000958488

RefSeq mRNA: 1 — MANE Select: NM_030641 NM_030641

CCDS: CCDS13919

Canonical transcript exons

ENST00000409652 — 3 exons

Exon	Start	End
ENSE00001577407	35656379	35656475
ENSE00001582038	35648446	35648623
ENSE00001586241	35658615	35668404

Expression profiles

Bgee: expression breadth ubiquitous, 245 present calls, max score 96.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 39.7067 / max 1221.9758, expressed in 1547 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
192023	15.8766	1088
192021	11.1303	1242
192020	5.7990	1337
192019	5.4171	1337
192017	0.7682	296
192022	0.4907	252
192028	0.1384	42
192018	0.0864	42

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pericardium	UBERON:0002407	96.90	gold quality
pylorus	UBERON:0001166	92.48	gold quality
sperm	CL:0000019	91.22	gold quality
buccal mucosa cell	CL:0002336	90.60	gold quality
monocyte	CL:0000576	89.91	gold quality
colonic epithelium	UBERON:0000397	89.77	gold quality
epithelium of nasopharynx	UBERON:0001951	89.61	gold quality
leukocyte	CL:0000738	89.57	gold quality
mononuclear cell	CL:0000842	89.41	gold quality
penis	UBERON:0000989	88.84	gold quality
vena cava	UBERON:0004087	88.72	gold quality
cardia of stomach	UBERON:0001162	88.64	gold quality
pharyngeal mucosa	UBERON:0000355	88.30	gold quality
palpebral conjunctiva	UBERON:0001812	88.02	gold quality
male germ cell	CL:0000015	87.68	gold quality
trigeminal ganglion	UBERON:0001675	87.63	gold quality
trachea	UBERON:0003126	87.34	gold quality
liver	UBERON:0002107	87.22	gold quality
urethra	UBERON:0000057	86.78	gold quality
synovial joint	UBERON:0002217	86.71	gold quality
superficial temporal artery	UBERON:0001614	86.61	gold quality
granulocyte	CL:0000094	86.59	gold quality
jejunal mucosa	UBERON:0000399	86.24	gold quality
adipose tissue	UBERON:0001013	86.19	gold quality
right lobe of liver	UBERON:0001114	86.01	gold quality
connective tissue	UBERON:0002384	85.71	gold quality
tonsil	UBERON:0002372	85.06	gold quality
lower lobe of lung	UBERON:0008949	85.01	gold quality
lymph node	UBERON:0000029	84.99	gold quality
superior surface of tongue	UBERON:0007371	84.82	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.65
E-ENAD-27	yes	4.84
E-GEOD-99795	no	58.19

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

276 targeting APOL6, 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-3163	100.00	77.23	8605
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5193	100.00	67.26	1744
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-LET-7F-2-3P	99.98	70.98	2588

Literature-anchored findings (GeneRIF, showing 6)

• APOL6 has been found only in humans (PMID:11374903)
• Apolipoprotein l6 is a novel proapoptotic Bcl-2 homology 3-only protein that induces mitochondria-mediated apoptosis in cancer cells (PMID:15671246)
• results suggest that ApoL6 regulates both apoptosis and autophagy in SMCs. IFNgamma-initiated, ApoL6-induced apoptosis in vascular cells may be an important factor causing plaque instability (PMID:21646352)
• Polymorphisms in FABP2 and APOL6, located at the predicted miRNAs binding sites, are identified to contribute to susceptibility to MetS in the Chinese Han population. (PMID:23911300)
• High APOL6 expression is associated with obesity and obesity-related cancers. (PMID:30423386)
• APOL6 has a high ranking for tumor aggressiveness, and interacts with genes in the STAT pathway, and with genes annotated as being part of the defense response, and the interferon signaling pathway. (PMID:32139709)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	apol	ENSDARG00000073718
mus_musculus	Apol6	ENSMUSG00000033576
caenorhabditis_elegans		WBGENE00017219
caenorhabditis_elegans		WBGENE00017220

Paralogs (6): APOL4 (ENSG00000100336), APOL1 (ENSG00000100342), APOL3 (ENSG00000128284), APOL5 (ENSG00000128313), APOL2 (ENSG00000128335), APOLD1 (ENSG00000178878)

Protein

Protein identifiers

Apolipoprotein L6 — Q9BWW8 (reviewed: Q9BWW8)

Alternative names: Apolipoprotein L-VI

All UniProt accessions (2): B3KTP4, Q9BWW8

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; highly expressed in the uterus, fetal brain and spinal cord, also detected in heart, liver, lung, colon, spleen, thymus, prostate, placenta, adrenal gland, salivary and mammary gland.

Similarity. Belongs to the apolipoprotein L family.

RefSeq proteins (1): NP_085144* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008405	ApoL	Family

Pfam: PF05461

UniProt features (4 total): chain 1, region of interest 1, compositionally biased region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BWW8-F1	54.86	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 203 (showing top): WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_LIPOPROTEIN_METABOLIC_PROCESS, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_10D_UP, CHARAFE_BREAST_CANCER_LUMINAL_VS_BASAL_DN, PALOMERO_GSI_SENSITIVITY_DN, GOBP_LIPID_LOCALIZATION, RIGGINS_TAMOXIFEN_RESISTANCE_DN, GOCC_NUCLEAR_BODY, FALVELLA_SMOKERS_WITH_LUNG_CANCER, GOMF_LIPID_BINDING, CHICAS_RB1_TARGETS_CONFLUENT, JOHNSTONE_PARVB_TARGETS_3_UP, MIYAGAWA_TARGETS_OF_EWSR1_ETS_FUSIONS_UP, BOSCO_INTERFERON_INDUCED_ANTIVIRAL_MODULE, ATF2_S_UP.V1_UP

GO Biological Process (2): lipid transport (GO:0006869), lipoprotein metabolic process (GO:0042157)

GO Molecular Function (2): 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
transport	1
lipid localization	1
protein metabolic process	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

744 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
APOL6	COMT	P21964	766
APOL6	PLAAT4	Q9UL19	461
APOL6	HPR	P00739	460
APOL6	PASD1	Q8IV76	433
APOL6	PARP9	Q8IXQ6	426
APOL6	OSBPL6	Q9BZF3	426
APOL6	MS4A12	Q9NXJ0	425
APOL6	GBP5	Q96PP8	425
APOL6	PXT1	Q8NFP0	421
APOL6	SCGB1D2	O95969	418
APOL6	TRIM5	Q9C035	404
APOL6	SAMHD1	Q9Y3Z3	396
APOL6	IFI44	Q8TCB0	395
APOL6	IFI16	Q16666	393
APOL6	YKT6	O15498	391

IntAct

27 interactions, top by confidence:

A	B	Type	Score
APOL6	GMCL1	psi-mi:“MI:0915”(physical association)	0.560
GMCL1	APOL6	psi-mi:“MI:0915”(physical association)	0.560
ADAMTSL4	APOL6	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-8	APOL6	psi-mi:“MI:0915”(physical association)	0.560
APOL6	LAMTOR3	psi-mi:“MI:0915”(physical association)	0.560
CCN3	APOL6	psi-mi:“MI:0915”(physical association)	0.560
FNTB	APOL6	psi-mi:“MI:0915”(physical association)	0.560
RGS13	APOL6	psi-mi:“MI:0915”(physical association)	0.560
TEPSIN	APOL6	psi-mi:“MI:0915”(physical association)	0.560
APOL6	IGF2R	psi-mi:“MI:0915”(physical association)	0.400
APOL6	MTNR1B	psi-mi:“MI:0915”(physical association)	0.000
APOL6	ADAMTSL4	psi-mi:“MI:0915”(physical association)	0.000
APOL6	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.000
FNTB	APOL6	psi-mi:“MI:0915”(physical association)	0.000
APOL6	LAMTOR3	psi-mi:“MI:0915”(physical association)	0.000
APOL6	CCN3	psi-mi:“MI:0915”(physical association)	0.000
APOL6	RGS13	psi-mi:“MI:0915”(physical association)	0.000
APOL6	TEPSIN	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (17): APOL6 (Two-hybrid), APOL6 (Two-hybrid), APOL6 (Two-hybrid), KRTAP10-8 (Two-hybrid), APOL6 (Affinity Capture-RNA), APOL6 (Two-hybrid), APOL6 (Two-hybrid), APOL6 (Two-hybrid), APOL6 (Two-hybrid), APOL6 (Two-hybrid), APOL6 (Two-hybrid), APOL6 (Two-hybrid), FNTB (Two-hybrid), APOL6 (Proximity Label-MS), APOL6 (Affinity Capture-MS)

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, Q6B959, Q96LR9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	59
Likely benign	13
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

858 predictions. Top by Δscore:

Variant	Effect	Δscore
22:35648619:AGAAG:A	donor_loss	1.0000
22:35648620:GAAGG:G	donor_loss	1.0000
22:35648622:AGGT:A	donor_loss	1.0000
22:35648623:GGTGA:G	donor_loss	1.0000
22:35648624:GTGAG:G	donor_loss	1.0000
22:35648625:T:G	donor_loss	1.0000
22:35658613:AG:A	acceptor_gain	1.0000
22:35658614:GG:G	acceptor_gain	1.0000
22:35658614:GGGAT:G	acceptor_gain	1.0000
22:35659446:GAAA:G	donor_gain	1.0000
22:35659450:G:GG	donor_gain	1.0000
22:35648605:A:T	donor_gain	0.9900
22:35648620:GAAG:G	donor_gain	0.9900
22:35658610:CTCA:C	acceptor_loss	0.9900
22:35658611:TCAG:T	acceptor_loss	0.9900
22:35658612:CA:C	acceptor_loss	0.9900
22:35658613:A:AG	acceptor_gain	0.9900
22:35658613:AGG:A	acceptor_gain	0.9900
22:35658614:G:GG	acceptor_gain	0.9900
22:35658614:G:T	acceptor_loss	0.9900
22:35658614:GGG:G	acceptor_gain	0.9900
22:35659447:A:T	donor_gain	0.9900
22:35667166:GTA:G	donor_gain	0.9900
22:35667169:G:GG	donor_gain	0.9900
22:35667800:TTACA:T	acceptor_loss	0.9900
22:35667801:TACAG:T	acceptor_loss	0.9900
22:35667802:ACAGG:A	acceptor_loss	0.9900
22:35667803:CA:C	acceptor_loss	0.9900
22:35667804:A:AG	acceptor_gain	0.9900
22:35667804:AGGAA:A	acceptor_loss	0.9900

AlphaMissense

2225 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:35658700:T:C	F46L	0.967
22:35658702:T:A	F46L	0.967
22:35658702:T:G	F46L	0.967
22:35658880:A:C	S106R	0.956
22:35658882:C:A	S106R	0.956
22:35658882:C:G	S106R	0.956
22:35658688:T:C	F42L	0.915
22:35658690:T:A	F42L	0.915
22:35658690:T:G	F42L	0.915
22:35658754:G:C	A64P	0.915
22:35658838:A:C	S92R	0.911
22:35658840:C:A	S92R	0.911
22:35658840:C:G	S92R	0.911
22:35658899:C:A	A112D	0.893
22:35658919:G:C	A119P	0.888
22:35659228:T:C	F222L	0.886
22:35659230:T:A	F222L	0.886
22:35659230:T:G	F222L	0.886
22:35658847:G:C	G95R	0.882
22:35658743:T:C	L60P	0.871
22:35659418:T:C	L285P	0.869
22:35658922:G:C	A120P	0.866
22:35658817:G:C	A85P	0.863
22:35658701:T:C	F46S	0.859
22:35658836:T:G	M91R	0.857
22:35658701:T:G	F46C	0.855
22:35658907:G:C	G115R	0.843
22:35658722:T:C	L53P	0.841
22:35658920:C:A	A119E	0.840
22:35658929:T:A	V122D	0.840

dbSNP variants (sampled 300 via entrez): RS1000219606 (22:35665950 A>G), RS1000315530 (22:35650137 G>A), RS1000515630 (22:35661878 G>T), RS1000515655 (22:35648099 C>G,T), RS1000855556 (22:35649220 G>A,C), RS1001001663 (22:35656643 A>C), RS1001325 (22:35654599 C>A,G,T), RS1001385153 (22:35663383 G>C,T), RS1001600194 (22:35660048 T>C), RS1001786769 (22:35668440 G>A), RS1001831892 (22:35666748 T>A), RS1001832152 (22:35649993 G>A), RS1001860369 (22:35668633 C>T), RS1002095315 (22:35654452 C>T), RS1002115921 (22:35667006 A>C)

Disease associations

OMIM: gene MIM:607256 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST005958_13	Waist-to-hip ratio adjusted for BMI (age >50)	1.000000e-06
GCST005962_33	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	6.000000e-06
GCST010242_116	HDL cholesterol levels	2.000000e-08
GCST010244_157	Triglyceride levels	2.000000e-11

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression, affects cotreatment	3
(+)-JQ1 compound	decreases expression	3
sodium arsenite	increases expression	2
Cisplatin	affects cotreatment, increases expression	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
Nickel	increases expression	2
Tobacco Smoke Pollution	decreases methylation, increases expression	2
urushiol	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, decreases reaction	1
mono-(2-ethylhexyl)phthalate	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	increases expression	1
zinc chromate	increases abundance, increases expression	1
nickel sulfate	increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
pentanal	decreases expression	1
chromium hexavalent ion	increases expression, increases abundance	1
perfluoro-n-nonanoic acid	increases expression	1
nutlin 3	affects cotreatment, increases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
prothioconazole	increases expression	1
Leflunomide	increases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Dactinomycin	increases expression, affects cotreatment	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1EK	Abcam A-549 APOL6 KO 2	Cancer cell line	Male
CVCL_B2M3	Abcam A-549 APOL6 KO 1	Cancer cell line	Male

Clinical trials (associated diseases)

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