APOL1

apolipoprotein L1, the group of Apolipoproteins

Basic information

Region (hg38): 22:36253070-36267530

Previous symbols: [ "APOL" ]

Links

ENSG00000100342 ∙ NCBI:8542 ∙ OMIM:603743 ∙ HGNC:618 ∙ Uniprot:O14791 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• focal segmental glomerulosclerosis 4, susceptibility to (Strong), mode of inheritance: AR
• focal segmental glomerulosclerosis 4, susceptibility to (Definitive), mode of inheritance: AR

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the APOL1 gene.

• not provided (120 variants)
• Focal segmental glomerulosclerosis 4, susceptibility to (21 variants)
• Inborn genetic diseases (15 variants)
• not specified (6 variants)
• Focal segmental glomerulosclerosis (3 variants)
• Hyalinosis, Segmental Glomerular (3 variants)
• Nephrotic range proteinuria (3 variants)
• Glomerulonephritis (2 variants)
• Sickled erythrocytes;Focal segmental glomerulosclerosis (2 variants)
• APOL1-associated kidney disease (2 variants)
• Steroid-resistant nephrotic syndrome;Focal segmental glomerulosclerosis (2 variants)
• Proteinuria (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the APOL1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				24	3	27
missense			46	4	10	60
nonsense			1			1
start loss						0
frameshift			1		1	2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			2	1		3
non coding				9	26	35
Total	0	0	48	37	40

Variants in APOL1

This is a list of pathogenic ClinVar variants found in the APOL1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
22-36253528-G-A			Benign (Nov 10, 2018)
22-36253745-G-A			Benign (Jun 25, 2020)
22-36253756-C-T			Benign (Aug 20, 2019)
22-36253920-C-T			Benign (Nov 10, 2018)
22-36253958-C-T		APOL1-related disorder	Benign/Likely benign (Oct 01, 2023)
22-36253990-T-C		APOL1-related disorder	Likely benign (Apr 12, 2021)
22-36254094-A-G			Likely benign (Aug 20, 2019)
22-36254175-C-G			Likely benign (Mar 11, 2020)
22-36254766-G-T			Likely benign (May 10, 2021)
22-36254910-G-A			Benign (Nov 10, 2018)
22-36254932-T-C		APOL1-related disorder	Likely benign (Jan 21, 2020)
22-36254978-G-A			Uncertain significance (Jul 19, 2022)
22-36254984-C-T			Uncertain significance (Jul 19, 2022)
22-36255185-T-G			Benign (Nov 10, 2018)
22-36256843-G-T			Benign (Aug 20, 2019)
22-36256885-C-T			Benign (Nov 10, 2018)
22-36256991-C-T			Likely benign (Mar 31, 2020)
22-36257101-T-G			Likely benign (Jun 13, 2023)
22-36257141-G-T			Uncertain significance (Nov 01, 2022)
22-36257229-G-A			Benign (Nov 10, 2018)
22-36257322-G-A			Likely benign (Nov 09, 2023)
22-36257323-C-A			Uncertain significance (Jul 25, 2022)
22-36257332-G-A		not specified	Uncertain significance (Feb 14, 2023)
22-36257339-G-T		not specified	Uncertain significance (Dec 28, 2023)
22-36257377-G-A			Uncertain significance (Jun 17, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
APOL1	protein_coding	protein_coding	ENST00000319136	6	14521

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000514	0.254	125721	0	27	125748	0.000107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.583	259	234	1.11	0.0000126	2701
Missense in Polyphen		70	57.422	1.219		745
Synonymous	-0.952	104	92.4	1.13	0.00000539	816
Loss of Function	-0.0236	8	7.93	1.01	3.36e-7	92

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000904	0.0000904
Ashkenazi Jewish	0.000496	0.000496
East Asian	0.000326	0.000326
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000616	0.0000615
Middle Eastern	0.000326	0.000326
South Asian	0.000196	0.000196
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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.
• Disease: DISEASE: Focal segmental glomerulosclerosis 4 (FSGS4) [MIM:612551]: A renal pathology defined by the presence of segmental sclerosis in glomeruli and resulting in proteinuria, reduced glomerular filtration rate and progressive decline in renal function. Renal insufficiency often progresses to end-stage renal disease, a highly morbid state requiring either dialysis therapy or kidney transplantation. {ECO:0000269|PubMed:20635188, ECO:0000269|PubMed:20647424}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: African trypanosomiasis - Homo sapiens (human);Vesicle-mediated transport;Post-translational protein phosphorylation;Post-translational protein modification;Metabolism of proteins;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs);Scavenging of heme from plasma;Binding and Uptake of Ligands by Scavenger Receptors (Consensus)

Intolerance Scores

• loftool: 0.976
• rvis_EVS: 1.45
• rvis_percentile_EVS: 95.12

Haploinsufficiency Scores

• pHI: 0.0163
• hipred: N
• hipred_score: 0.112
• ghis: 0.390

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.417

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Zebrafish Information Network

• Gene name: apol1
• Affected structure: podocyte
• Phenotype tag: abnormal
• Phenotype quality: disorganized

Gene ontology

• Biological process: lipid transport;receptor-mediated endocytosis;cholesterol metabolic process;cytolysis;killing of cells of other organism;lipoprotein metabolic process;post-translational protein modification;cellular protein metabolic process;innate immune response;chloride transmembrane transport
• Cellular component: extracellular region;extracellular space;endoplasmic reticulum lumen;intrinsic component of membrane;very-low-density lipoprotein particle;high-density lipoprotein particle;blood microparticle
• Molecular function: chloride channel activity;protein binding;lipid binding