rs73885319

badMag 8.5

This is a variant in the APOL1 gene that changes a serine to an glycine.

Key Literature Trait Associations

Focal Segmental Glomerulosclerosis

The APOL1 G1 haplotype (including rs73885319-G) confers dramatically elevated FSGS risk in individuals of African ancestry under a recessive model. The landmark Genovese et al. (2010) Science study found an OR of 10.5 (95% CI 6.0–18.4) for FSGS among individuals carrying two APOL1 risk alleles. A pediatric cohort study (Durand et al., 2023) confirmed APOL1 association with biopsy-proven FSGS in African American children (OR 25.8, 95% CI 7.1–94.0). The effect is predominantly seen in African-ancestry populations and follows a recessive inheritance pattern, meaning single-allele carriers have minimal excess risk.

Genovese G et al. “Association of trypanolytic ApoL1 variants with kidney disease in African Americans.” Science (new York, N.y.) (2010)
Allele G
OR 10.50
p 1.0e-23
N 385
Small GWAS
African American
Durand A et al. “Identification of Novel Genetic Risk Factors for Focal Segmental Glomerulosclerosis in Children: Results From the Chronic Kidney Disease in Children (CKiD) Cohort.” American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation (2023)
Allele G
OR 25.80
p 8.6e-7
N 140
Preliminary work
African American

End-stage kidney disease

APOL1 G1 (rs73885319) confers substantially elevated risk of hypertension-attributed end-stage kidney disease (ESKD) in African Americans, operating under a recessive model requiring two risk alleles. The discovery study (Genovese et al., 2010) reported OR=7.3 (95% CI 5.6–9.5) for hypertensive ESKD. African Americans carrying two APOL1 risk alleles face an estimated 7- to 10-fold greater risk of nondiabetic ESRD compared to those carrying zero or one risk allele, accounting for a large proportion of the excess kidney disease burden in this population.

Genovese G et al. “Association of trypanolytic ApoL1 variants with kidney disease in African Americans.” Science (new York, N.y.) (2010)
Allele G
OR 7.30
p 1.0e-30
N 1,872
Large GWAS
African American
Jagannathan R et al. “Association Between APOL1 Genotype and Kidney Diseases and Annual Kidney Function Change: A Systematic Review and Meta-Analysis of the Prospective Studies.” International Journal of Nephrology and Renovascular Disease (2021)
Allele G
OR —
p —
Meta-analysis
African American

Chronic Kidney Disease

APOL1 high-risk genotypes (two copies of G1 and/or G2 alleles) are strongly associated with incident CKD and accelerated progression to ESKD, predominantly in African-ancestry populations. A systematic review and meta-analysis of 10 prospective studies (Jagannathan et al., 2021) found high-risk APOL1 genotype associated with CKD incidence (RR 1.41, 95% CI 1.14–1.75), CKD-to-ESKD progression (RR 1.70, 95% CI 1.44–2.01), and annual eGFR decline of −0.55 mL/min/1.73m². The VA Million Veteran Program (Verma et al., 2024, n=632,703) identified rs73885319 as a genome-wide significant locus for kidney failure in African American veterans.

Jagannathan R et al. “Association Between APOL1 Genotype and Kidney Diseases and Annual Kidney Function Change: A Systematic Review and Meta-Analysis of the Prospective Studies.” International Journal of Nephrology and Renovascular Disease (2021)
Allele G
OR —
p —
Meta-analysis
African American
Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)
Allele G
OR —
β 0.281 ±0.021
p 2.0e-23
N 632,703
Major Consortium StudyLarge GWAS
African American

Glomerulonephritis

rs73885319 within APOL1 is genome-wide significantly associated with glomerulonephritis in African American veterans in the VA Million Veteran Program (Verma et al., 2024). The A allele at rs73885319 showed a protective/decreasing directional beta in the MVP analysis context, but in the broader APOL1 biology the G1 haplotype (tagged by the G allele) drives glomerulonephritis risk. The MVP association (p=2×10⁻¹⁵, beta=0.46, n=121,356 African Americans) provides large-scale GWAS confirmation of APOL1's role in inflammatory glomerular disease.

Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)
Allele A
OR —
β 0.459 ±0.056
p 2.0e-15
N 121,356
Major Consortium StudyLarge GWAS
African American

Kidney transplant outcomes

rs73885319 in APOL1 is significantly associated with kidney transplant outcomes in the VA Million Veteran Program (Verma et al., 2024), reaching genome-wide significance at p=1×10⁻³⁶ in the largest multi-ancestry GWAS to date. The association reflects both the elevated rate of ESKD (leading to transplantation) in APOL1 risk-variant carriers, and evidence that donor APOL1 genotype influences transplant graft survival. APOL1 high-risk donor kidneys have been associated with accelerated graft loss in recipients regardless of recipient genotype.

Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)
Allele A
OR —
β 0.638
p 1.0e-36
N 632,703
Major Consortium StudyLarge GWAS
multi-ancestry
▶

GWAS Catalog Trait Associations (14)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

secondary hyperparathyroidism of renal origin

Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)
Allele A
OR 0.32
p 6.0e-31
N 628,937
Major Consortium StudyLarge GWAS
multi-ancestry

Proteinuria

Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)
Allele A
OR 0.23
p 6.0e-22
N 625,172
Major Consortium StudyLarge GWAS
multi-ancestry

mineral metabolism disease

Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)
Allele A
OR 0.15
p 3.0e-14
N 114,875
Major Consortium StudyLarge GWAS
African American or Afro-Caribbean

vascular disease

Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)
Allele A
OR 0.34
p 1.0e-13
N 119,522
Major Consortium StudyLarge GWAS
African American or Afro-Caribbean

hyperparathyroidism

Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)
Allele A
OR 0.24
p 4.0e-11
N 120,584
Major Consortium StudyLarge GWAS
African American or Afro-Caribbean

blood urea nitrogen amount

Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)
Allele A
OR 0.04
p 7.0e-13
N 598,949
Major Consortium StudyLarge GWAS
multi-ancestry

chronic kidney disease

Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)
Allele A
OR 0.12
p 6.0e-15
N 118,108
Major Consortium StudyLarge GWAS
African American or Afro-Caribbean
Lin BM et al. “Genetics of Chronic Kidney Disease Stages Across Ancestries: The PAGE Study.” Frontiers in Genetics 10:494 (2019)
Allele A
OR 1.51
p 2.0e-9
N 32,799
Large GWAS
multi-ancestry

glomerular filtration rate

Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)
Allele A
OR 0.06
p 3.0e-28
N 571,227
Major Consortium StudyLarge GWAS
multi-ancestry

glomerulonephritis

Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)
Allele A
OR 0.46
p 2.0e-15
N 121,356
Major Consortium StudyLarge GWAS
African American or Afro-Caribbean

kidney disease

Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)
Allele A
OR 0.30
p 7.0e-21
N 119,579
Major Consortium StudyLarge GWAS
African American or Afro-Caribbean
▶

ClinVar annotation

Pathogenic★★★☆
8 submitters20 publications

APOL1-associated kidney disease; Focal segmental glomerulosclerosis (FSGS); Focal segmental glomerulosclerosis 4, susceptibility to (FSGS4); Focal segmental glomerulosclerosis, susceptibility to; Glomerulonephritis; Hyalinosis, Segmental Glomerular; Nephrotic range proteinuria; Proteinuria; Sickled erythrocytes; Steroid-resistant nephrotic syndrome; not specified

View on ClinVar →
▶

Research that mentions this SNP (1)

▶
Missense mutations in the APOL1 gene are highly associated with end stage kidney disease risk previously attributed to the MYH9 gene
AssociationN=955Shay Tzur et al.(2010)· Human Genetics

Two APOL1 missense mutations (S342G and I384M, rs73885319 and rs60910145) are identified as strongly associated with end-stage kidney disease risk in African and Hispanic American populations, with odds ratios of 2.22-6.7 and p-values as low as 2.38E-08, explaining genetic associations previously attributed to nearby MYH9 variants. The mutations show strong additive inheritance patterns and geographic distribution consistent with African ancestry risk.

Traits studied:End-stage kidney diseaseFocal segmental glomerulosclerosisHIV-associated nephropathyHypertension-affiliated chronic kidney disease
PubMedDOIMetascience Observatory

Gene information from NCBI Gene. Variant classifications from ClinVar.

Community Wiki

No community notes yet for this variant. Sign in to start one.

Comments

Sign in to join the discussion.

Loading comments…