APOL4

Summary

APOL4 (apolipoprotein L4, HGNC:14867) is a protein-coding gene on chromosome 22q12.3, encoding Apolipoprotein L4 (Q9BPW4). May play a role in lipid exchange and transport throughout the body.

This gene encodes a member of the apolipoprotein L family. The encoded protein may play a role in lipid exchange and transport throughout the body, as well as in reverse cholesterol transport from peripheral cells to the liver. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 80832 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 32 total
• MANE Select transcript: NM_001386885

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14867
Approved symbol	APOL4
Name	apolipoprotein L4
Location	22q12.3
Locus type	gene with protein product
Status	Approved
Aliases	APOLIV
Ensembl gene	ENSG00000100336
Ensembl biotype	protein_coding
OMIM	607254
Entrez	80832

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 10 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000332987, ENST00000352371, ENST00000397275, ENST00000419360, ENST00000436763, ENST00000449084, ENST00000457630, ENST00000480236, ENST00000493203, ENST00000613247, ENST00000616056, ENST00000683024, ENST00000684666, ENST00000880614

RefSeq mRNA: 4 — MANE Select: NM_001386885 NM_001386885, NM_030643, NM_145660, NM_145661

CCDS: CCDS74851, CCDS74852, CCDS93158

Canonical transcript exons

ENST00000683024 — 4 exons

Exon	Start	End
ENSE00001742279	36189128	36191912
ENSE00003510938	36195311	36195437
ENSE00003513703	36199330	36199376
ENSE00003918914	36201700	36201809

Expression profiles

Bgee: expression breadth ubiquitous, 203 present calls, max score 86.29.

FANTOM5 (CAGE): breadth broad, TPM avg 4.1849 / max 416.7855, expressed in 510 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
193867	2.9620	395
193868	0.6688	271
193866	0.3544	87
193865	0.1327	45
193869	0.0429	23
193870	0.0241	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adenohypophysis	UBERON:0002196	86.29	gold quality
right uterine tube	UBERON:0001302	85.78	gold quality
tendon of biceps brachii	UBERON:0008188	84.96	gold quality
pituitary gland	UBERON:0000007	83.65	gold quality
pancreatic ductal cell	CL:0002079	83.42	silver quality
omental fat pad	UBERON:0010414	81.47	gold quality
peritoneum	UBERON:0002358	81.42	gold quality
vermiform appendix	UBERON:0001154	80.83	gold quality
gall bladder	UBERON:0002110	80.45	gold quality
adipose tissue of abdominal region	UBERON:0007808	80.24	gold quality
prostate gland	UBERON:0002367	79.82	gold quality
ganglionic eminence	UBERON:0004023	78.96	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.48	gold quality
epithelial cell of pancreas	CL:0000083	78.39	gold quality
saliva-secreting gland	UBERON:0001044	78.30	gold quality
endometrium	UBERON:0001295	78.30	gold quality
minor salivary gland	UBERON:0001830	77.85	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	77.85	gold quality
subcutaneous adipose tissue	UBERON:0002190	77.79	gold quality
tibial nerve	UBERON:0001323	77.69	gold quality
colonic epithelium	UBERON:0000397	77.32	gold quality
upper lobe of left lung	UBERON:0008952	77.27	gold quality
apex of heart	UBERON:0002098	77.00	gold quality
urinary bladder	UBERON:0001255	76.17	gold quality
upper lobe of lung	UBERON:0008948	76.17	gold quality
smooth muscle tissue	UBERON:0001135	75.79	gold quality
left uterine tube	UBERON:0001303	75.77	gold quality
caecum	UBERON:0001153	75.66	gold quality
mouth mucosa	UBERON:0003729	75.56	gold quality
skin of abdomen	UBERON:0001416	74.95	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.64

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): STAT1

miRNA regulators (miRDB)

96 targeting APOL4, 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-5193	100.00	67.26	1744
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-539-5P	99.93	70.30	2855

Literature-anchored findings (GeneRIF, showing 2)

• APOL4 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)

Cross-species orthologs

13 orthologs

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

Paralogs (6): APOL1 (ENSG00000100342), APOL3 (ENSG00000128284), APOL5 (ENSG00000128313), APOL2 (ENSG00000128335), APOLD1 (ENSG00000178878), APOL6 (ENSG00000221963)

Protein

Protein identifiers

Apolipoprotein L4 — Q9BPW4 (reviewed: Q9BPW4)

Alternative names: Apolipoprotein L-IV

All UniProt accessions (6): Q9BPW4, B1AHJ0, B1AHJ2, E9PS31, F5H1P9, Q9BRG6

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in lipid exchange and transport throughout the body. May participate in reverse cholesterol transport from peripheral cells to the liver.

Subcellular location. Secreted.

Tissue specificity. Widely expressed; the highest levels are in spinal cord, placenta, adrenal gland; also detected in spleen, bone marrow, uterus, trachea, mammary gland and testis; levels are low in brain, heart and pancreas.

Similarity. Belongs to the apolipoprotein L family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9BPW4-1	1, B	yes
Q9BPW4-2	2, A
Q9BPW4-3	3

RefSeq proteins (4): NP_001373814, NP_085146, NP_663693, NP_663694 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008405	ApoL	Family

Pfam: PF05461

UniProt features (10 total): sequence variant 6, splice variant 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BPW4-F1	54.08	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 73 (showing top): GOBP_LIPOPROTEIN_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_LIPID_LOCALIZATION, GOMF_LIPID_BINDING, MARTENS_TRETINOIN_RESPONSE_UP, MAFG_TARGET_GENES, SKIL_TARGET_GENES, MIR539_5P, MIR513B_5P, MIR3140_3P, MIR2110, MIR450A_2_3P, MIR149_5P, MIR4457, GSE11864_CSF1_IFNG_VS_CSF1_IFNG_PAM3CYS_IN_MAC_UP

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

GO Molecular Function (2): lipid binding (GO:0008289), protein binding (GO:0005515)

GO Cellular Component (2): obsolete extracellular space (GO:0005615), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
primary metabolic process	1
transport	1
lipid localization	1
protein metabolic process	1
cellular anatomical structure	1

Protein interactions and networks

STRING

584 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
APOL4	COMT	P21964	722
APOL4	CHRM4	P08173	490
APOL4	PRODH	O43272	473
APOL4	LGALS14	Q8TCE9	449
APOL4	PRODH	O43272	444
APOL4	LGALS13	Q9UHV8	423
APOL4	PDE4B	Q07343	423
APOL4	OR10H5	Q8NGA6	422
APOL4	NPIPB8	E9PQR5	418
APOL4	OR10H1	Q9Y4A9	415
APOL4	TUFM	P49411	402
APOL4	SYN2	Q92777	373
APOL4	NPIPB9	F8W1W9	371
APOL4	MYH9	P35579	359
APOL4	APOO	Q9BUR5	355

IntAct

2 interactions, top by confidence:

A	B	Type	Score
TFAP2C	APOL4	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (2): LNX1 (Two-hybrid), APOL4 (Two-hybrid)

ESM2 similar proteins: A0A140LIF8, A0A2P1BRP3, A0A386CAB9, A0JN92, A1A4Y4, O14791, P27473, P59045, P86448, P86449, Q0GUM3, Q13075, Q3B7D9, Q3T9E4, Q3TL54, Q53G44, Q5NCI0, Q5RFJ8, Q60766, Q62293, Q66X01, Q66X03, Q66X05, Q66X22, Q6AYC2, Q6ZSC3, Q7Z745, Q84WJ0, Q86W28, Q8BV66, Q8BVM9, Q8C6J9, Q8CBA2, Q8CCN1, Q8TCB0, Q8TCY9, Q8TD90, Q90597, Q99388, Q99J64

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	15
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

726 predictions. Top by Δscore:

Variant	Effect	Δscore
22:36195308:TAC:T	donor_loss	1.0000
22:36195309:AC:A	donor_loss	1.0000
22:36195310:C:CA	donor_loss	1.0000
22:36195342:T:TA	donor_gain	1.0000
22:36195433:CTTTT:C	acceptor_gain	1.0000
22:36195434:TTTT:T	acceptor_gain	1.0000
22:36195435:TTTCT:T	acceptor_loss	1.0000
22:36195436:TT:T	acceptor_gain	1.0000
22:36195437:TCT:T	acceptor_loss	1.0000
22:36195438:C:CC	acceptor_gain	1.0000
22:36195439:T:C	acceptor_loss	1.0000
22:36195442:T:C	acceptor_gain	1.0000
22:36195442:T:TC	acceptor_gain	1.0000
22:36191911:CC:C	acceptor_gain	0.9900
22:36191911:CCCTG:C	acceptor_loss	0.9900
22:36191912:CC:C	acceptor_gain	0.9900
22:36191913:C:CC	acceptor_gain	0.9900
22:36191920:A:T	acceptor_gain	0.9900
22:36195435:TTT:T	acceptor_gain	0.9900
22:36195449:C:CT	acceptor_gain	0.9900
22:36195450:A:T	acceptor_gain	0.9900
22:36199376:CCT:C	acceptor_gain	0.9900
22:36204621:AACTT:A	donor_loss	0.9900
22:36204622:ACTT:A	donor_loss	0.9900
22:36204623:CTTA:C	donor_loss	0.9900
22:36204624:TTACC:T	donor_loss	0.9900
22:36204625:TA:T	donor_loss	0.9900
22:36204626:ACC:A	donor_loss	0.9900
22:36204627:C:T	donor_loss	0.9900
22:36204638:T:TA	donor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000063742 (22:36199218 C>A,T), RS1000183277 (22:36189832 C>T), RS1000213055 (22:36194598 G>C), RS1000642938 (22:36194721 G>T), RS1000709853 (22:36205951 C>G,T), RS1000899762 (22:36190292 T>A,C), RS1000983616 (22:36206568 C>T), RS1001079888 (22:36206127 A>G), RS1001342273 (22:36198282 C>G), RS1001361092 (22:36202598 C>A,T), RS1001392323 (22:36202448 C>A,T), RS1001533798 (22:36193724 A>G), RS1001613503 (22:36206817 C>A,T), RS1001797129 (22:36194071 C>T), RS1001991482 (22:36199833 G>T)

Disease associations

OMIM: gene MIM:607254 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Lead	affects expression, decreases expression	2
Nickel	increases expression	2
Particulate Matter	increases expression, increases abundance	2
aristolochic acid I	increases expression	1
TL8-506	affects cotreatment, increases expression	1
propionaldehyde	decreases expression	1
bisphenol A	affects cotreatment, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
aflatoxin B2	increases methylation	1
pentanal	decreases expression	1
CGP 52608	affects binding, increases reaction	1
theaflavin-3,3’-digallate	affects expression	1
Bortezomib	decreases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
1-Methyl-3-isobutylxanthine	increases expression, affects cotreatment	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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