APOL5

Summary

APOL5 (apolipoprotein L5, HGNC:14869) is a protein-coding gene on chromosome 22q12.3, encoding Apolipoprotein L5 (Q9BWW9). 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 80831 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 81 total
• GTEx eGene: eQTL in 9 tissues, sQTL in 0 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.09 (unconstrained)
• MANE Select transcript: NM_030642
• Notable: 81 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14869
Approved symbol	APOL5
Name	apolipoprotein L5
Location	22q12.3
Locus type	gene with protein product
Status	Approved
Aliases	APOLV
Ensembl gene	ENSG00000128313
Ensembl biotype	protein_coding
OMIM	607255
Entrez	80831

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

MANE Select: ENST00000249044

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1

ENST00000249044

RefSeq mRNA: 1 — MANE Select: NM_030642 NM_030642

CCDS: CCDS13920

Canonical transcript exons

ENST00000249044 — 5 exons

Exon	Start	End
ENSE00000880021	35726211	35727194
ENSE00000880022	35728723	35728904
ENSE00000911244	35717872	35717926
ENSE00000936034	35729354	35729483
ENSE00001275737	35720568	35720654

Expression profiles

Bgee: expression breadth broad, 36 present calls, max score 84.33.

Highest expression (Bgee): male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, hindlimb stylopod muscle, skeletal muscle tissue, muscle of leg.

Genetic regulation across tissues (GTEx eQTL / sQTL)

APOL5 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 9 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

9 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Muscle Skeletal	eqtl	2.0e-64	-0.55	22:35685923:A:C
Liver	eqtl	2.5e-23	+0.75	22:35726883:C:T
Adipose Subcutaneous	eqtl	8.6e-23	-0.47	22:35646939:C:T
Nerve Tibial	eqtl	7.9e-17	-0.48	22:35646939:C:T
Breast Mammary Tissue	eqtl	2.9e-10	-0.40	22:35646939:C:T
Adipose Visceral Omentum	eqtl	3.0e-07	-0.36	22:35646939:C:T
Thyroid	eqtl	3.9e-06	-0.30	22:35646939:C:T
Heart Left Ventricle	eqtl	3.5e-04	-0.31	22:35642029:C:T
Artery Coronary	eqtl	1.6e-03	-0.37	22:35646939:C:T

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.33	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.37	silver quality
hindlimb stylopod muscle	UBERON:0004252	59.00	gold quality
skeletal muscle tissue	UBERON:0001134	57.41	gold quality
muscle of leg	UBERON:0001383	53.23	gold quality
gastrocnemius	UBERON:0001388	50.61	gold quality
muscle tissue	UBERON:0002385	50.05	gold quality
right lobe of liver	UBERON:0001114	47.75	gold quality
lower esophagus mucosa	UBERON:0035834	46.69	silver quality
liver	UBERON:0002107	46.66	gold quality
gall bladder	UBERON:0002110	44.48	gold quality
apex of heart	UBERON:0002098	42.11	silver quality
prefrontal cortex	UBERON:0000451	40.60	gold quality
heart left ventricle	UBERON:0002084	39.53	gold quality
left testis	UBERON:0004533	39.30	gold quality
testis	UBERON:0000473	38.78	gold quality
subcutaneous adipose tissue	UBERON:0002190	38.61	silver quality
primary visual cortex	UBERON:0002436	38.45	silver quality
anterior cingulate cortex	UBERON:0009835	37.98	silver quality
thoracic mammary gland	UBERON:0005200	37.75	gold quality
frontal cortex	UBERON:0001870	37.67	gold quality
ganglionic eminence	UBERON:0004023	37.36	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
right testis	UBERON:0004534	37.14	gold quality
heart	UBERON:0000948	37.01	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	36.24	silver quality
bone marrow cell	CL:0002092	36.16	gold quality
mucosa of stomach	UBERON:0001199	36.03	silver quality
Brodmann (1909) area 9	UBERON:0013540	35.91	silver quality
adipose tissue	UBERON:0001013	35.90	silver quality
cerebral cortex	UBERON:0000956	35.87	gold quality
right coronary artery	UBERON:0001625	35.62	gold quality
mucosa of transverse colon	UBERON:0004991	35.09	gold quality
duodenum	UBERON:0002114	32.80	gold quality
left coronary artery	UBERON:0001626	31.86	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
lymph node	UBERON:0000029	31.47	gold quality
descending thoracic aorta	UBERON:0002345	31.31	gold quality
superior frontal gyrus	UBERON:0002661	31.10	gold quality
material anatomical entity	UBERON:0000465	30.76	gold quality
multicellular organism	UBERON:0000468	30.76	gold quality
brain	UBERON:0000955	30.31	gold quality
adrenal tissue	UBERON:0018303	30.24	gold quality
tonsil	UBERON:0002372	30.06	gold quality
vermiform appendix	UBERON:0001154	30.02	silver quality
rectum	UBERON:0001052	29.92	gold quality
tibial artery	UBERON:0007610	29.88	silver quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
popliteal artery	UBERON:0002250	29.78	silver quality
cortex of kidney	UBERON:0001225	28.93	silver quality
temporal lobe	UBERON:0001871	28.77	silver quality
blood	UBERON:0000178	28.52	gold quality
smooth muscle tissue	UBERON:0001135	28.45	silver quality
amygdala	UBERON:0001876	28.39	silver quality
islet of Langerhans	UBERON:0000006	28.37	gold quality
endometrium	UBERON:0001295	27.73	gold quality
muscle layer of sigmoid colon	UBERON:0035805	27.38	gold quality
fallopian tube	UBERON:0003889	26.91	gold quality
kidney	UBERON:0002113	26.68	gold quality
small intestine	UBERON:0002108	26.56	gold quality
left uterine tube	UBERON:0001303	26.55	gold quality
pancreas	UBERON:0001264	26.50	gold quality
leukocyte	CL:0000738	26.48	gold quality
monocyte	CL:0000576	26.37	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality
placenta	UBERON:0001987	25.82	gold quality
ovary	UBERON:0000992	25.56	gold quality
small intestine Peyer’s patch	UBERON:0003454	25.49	gold quality
right ovary	UBERON:0002118	25.06	gold quality
nucleus accumbens	UBERON:0001882	24.86	gold quality
lung	UBERON:0002048	24.71	gold quality
left ovary	UBERON:0002119	24.61	gold quality
body of stomach	UBERON:0001161	24.52	gold quality
skin of leg	UBERON:0001511	24.49	gold quality
right lung	UBERON:0002167	24.49	gold quality
body of pancreas	UBERON:0001150	24.27	gold quality
zone of skin	UBERON:0000014	24.09	gold quality
vagina	UBERON:0000996	23.66	gold quality
prostate gland	UBERON:0002367	23.37	gold quality
corpus callosum	UBERON:0002336	23.36	gold quality
skin of abdomen	UBERON:0001416	23.25	gold quality
adrenal gland	UBERON:0002369	23.14	gold quality
transverse colon	UBERON:0001157	23.10	gold quality
body of uterus	UBERON:0009853	23.05	gold quality
right adrenal gland	UBERON:0001233	22.82	gold quality
adult mammalian kidney	UBERON:0000082	22.52	gold quality
ectocervix	UBERON:0012249	22.22	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	21.93	gold quality
left adrenal gland	UBERON:0001234	21.59	gold quality
right adrenal gland cortex	UBERON:0035827	21.50	gold quality
upper lobe of left lung	UBERON:0008952	21.43	gold quality
spleen	UBERON:0002106	21.11	gold quality
granulocyte	CL:0000094	20.63	gold quality
left adrenal gland cortex	UBERON:0035825	19.74	gold quality
adenohypophysis	UBERON:0002196	19.40	gold quality
right uterine tube	UBERON:0001302	16.49	gold quality
metanephros cortex	UBERON:0010533	15.43	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.66

HPA expression

RNA tissue specificity: Tissue enhanced

18 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Tongue	tissue	1.9
Skeletal muscle	tissue	1.3
Cerebral cortex	tissue	0.4
Hippocampal formation	tissue	0.3
Testis	tissue	0.2
Heart muscle	tissue	0.2
Amygdala	tissue	0.2
Cerebellum	tissue	0.2
Pons	tissue	0.1
Adipose tissue	tissue	0.1
Basal ganglia	tissue	0.1
Medulla oblongata	tissue	0.1
Hypothalamus	tissue	0.1
Gallbladder	tissue	0.1
Hippocampus	tissue	0.1
Postcentral gyrus	tissue	0.1
Retrosplenial cortex	tissue	0.1
Occipital cortex	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 68; highest nTPM — Parieto-insular cortex (0.4), Hippocampus, CA3 (0.3), Posterior insular cortex (0.3), Angular gyrus (white matter) (0.2), Anterior insular cortex, ventral (0.2).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting APOL5 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

8 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-12121	99.99	66.64	255
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-4317	98.49	67.09	987
HSA-MIR-1912-5P	97.94	67.98	832
HSA-MIR-3152-5P	96.98	66.88	819
HSA-MIR-12128	96.67	66.98	1471

Functional genomics

gnomAD constraint: pLI 4.32e-08, LOEUF 1.09, missense Z 0.586 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000249044 splits into 3 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
22:35,717,872–35,726,712	254 / 254.7	1.00	no
22:35,726,713–35,726,825	22 / 46.6	0.47	no
22:35,726,826–35,728,895	238 / 229.1	1.04	no

Literature-anchored findings (GeneRIF, showing 1)

• APOL5 has been found only in humans (PMID:11374903)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
caenorhabditis_elegans		WBGENE00017219
caenorhabditis_elegans		WBGENE00017220

Paralogs (6): APOL4 (ENSG00000100336), APOL1 (ENSG00000100342), APOL3 (ENSG00000128284), APOL2 (ENSG00000128335), APOLD1 (ENSG00000178878), APOL6 (ENSG00000221963)

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
APOL3	protein-coding	80833
MB	protein-coding	4151
APOL6	protein-coding	80830

Protein

Protein identifiers

Apolipoprotein L5 — Q9BWW9 (reviewed: Q9BWW9)

Alternative names: Apolipoprotein L-V

All UniProt accessions (1): Q9BWW9

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. Low level of expression; detected in uterus, testis, skeletal muscle and stomach.

Similarity. Belongs to the apolipoprotein L family.

RefSeq proteins (1): NP_085145* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008405	ApoL	Family

Pfam: PF05461

UniProt features (8 total): sequence variant 4, compositionally biased region 2, chain 1, region of interest 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BWW9-F1	41.66	0.00

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins, UniProt - Evidence at transcript level

Protein evidence: Evidence at transcript 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: 22 (showing top): GOBP_LIPOPROTEIN_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_LIPID_LOCALIZATION, GOMF_PROTEIN_LIPID_COMPLEX_BINDING, GOMF_LIPID_BINDING, GOMF_HIGH_DENSITY_LIPOPROTEIN_PARTICLE_BINDING, GOMF_PROTEIN_CONTAINING_COMPLEX_BINDING, ZNF22_TARGET_GENES, MIR4317, chr22q12, DESCARTES_MAIN_FETAL_SMOOTH_MUSCLE_CELLS, DESCARTES_FETAL_HEART_SMOOTH_MUSCLE_CELLS, NAKAYA_B_CELL_FLUARIX_FLUVIRIN_AGE_18_50YO_7DY_DN, GSE17974_IL4_AND_ANTI_IL12_VS_UNTREATED_0.5H_ACT_CD4_TCELL_UP, GSE22886_CD8_TCELL_VS_BCELL_NAIVE_DN

GO Biological Process (3): lipid metabolic process (GO:0006629), lipid transport (GO:0006869), lipoprotein metabolic process (GO:0042157)

GO Molecular Function (2): high-density lipoprotein particle binding (GO:0008035), lipid binding (GO:0008289)

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

GO top-level categories

8 GO namespaces:

Category	Terms
cellular anatomical structure	3
primary metabolic process	1
transport	1
lipid localization	1
protein metabolic process	1
lipoprotein particle binding	1
binding	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

showing 15 of 290 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
APOL5	COMT	P21964	671
APOL5	CIMIP2C	A6NJV1	496
APOL5	APOO	Q9BUR5	470
APOL5	HPR	P00739	468
APOL5	APOC4	P55056	401
APOL5	APOLD1	Q96LR9	391
APOL5	OR10H5	Q8NGA6	387
APOL5	APOL1	O14791	363
APOL5	APOF	Q13790	357
APOL5	APOL4	Q9BPW4	351
APOL5	APOM	O95445	323
APOL5	NPIPB9	F8W1W9	322
APOL5	NT5DC4	Q86YG4	309
APOL5	ZNF441	Q8N8Z8	297
APOL5	HP	P00737	293

IntAct

Human interaction partners of APOL5 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

8 partners by confidence:

Partner	Interaction type	MIscore	Records
ABL1	physical association	0.400	1
CLTCL1	physical association	0.400	1
CRK	physical association	0.400	1
FYN	physical association	0.400	1
GRB2	physical association	0.400	1
NCK1	physical association	0.400	1
PIK3R1	physical association	0.400	1
SRC	physical association	0.400	1

BioGRID (2 interactions; top human partners by supporting records): CLTCL1 (Affinity Capture-MS), CUL3 (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for APOL5: 81 ClinVar records (0 pathogenic / likely pathogenic); 3 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	69
Likely benign	6
Benign	2

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 14 predictions of 364):

Position(s)	Effect	Δscore	Sites
22:35717927–35717928	donor_loss	0.9800	5
22:35720461	acceptor_gain	0.9700
22:35726397	acceptor_gain	0.9500
22:35726395	acceptor_gain	0.9100
22:35726307	acceptor_gain	0.8700
22:35728754	acceptor_gain	0.8000
22:35720469	acceptor_gain	0.7900
22:35720473	acceptor_gain	0.7900
22:35727129	donor_gain	0.7900
22:35729346	acceptor_gain	0.7700

AlphaMissense

112 missense substitutions predicted likely pathogenic (of 2,813 scored), across 62 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
F106	5	0.786	0.877
M151	5	0.670	0.676
F255	4	0.800	0.869
G173	4	0.612	0.691
G175	4	0.605	0.645
S166	3	0.846	0.846
F102	3	0.824	0.824
F280	3	0.815	0.815
F270	3	0.802	0.802
F262	3	0.796	0.796
F111	3	0.730	0.730
F301	3	0.721	0.721
F215	3	0.706	0.706
S142	3	0.659	0.659
F79	3	0.581	0.581
R330	2	0.733	0.733
A124	2	0.722	0.769
K110	2	0.712	0.712
A141	2	0.710	0.720
R199	2	0.695	0.695

HPA cancer prognostics

RNA cancer specificity: Not detected

Disease associations

OMIM: gene MIM:607255 | disease phenotypes:

GWAS associations

3 associations:

Study	Trait	p-value
GCST005958_5	Waist-to-hip ratio adjusted for BMI (age >50)	1e-6
GCST002301_5	Body mass index	3e-6
GCST005962_58	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	6e-6

EFO canonical traits (from GWAS)

4 canonical traits:

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Rotenone	increases expression	1

Clinical trials (associated diseases)

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