Urinary

Kidney Stones

Reviewed September 18, 2026

A common, painful condition with a real genetic component. A whole-genome study of Iceland's own population found a risk variant in a gene that normally helps keep calcium crystals from forming in urine in the first place.

What this condition connects to

Kidney Stones Variant: rs1256328 rs1256328 Variant Kidney Stones Kidney Stones Urinary
Prevalence
A whole-genome sequencing study of 2,636 Icelanders, imputed into 5,419 kidney stone cases and 279,870 controls, identified a risk variant in ALPL (rs1256328, odds ratio 1.21, P = 5.8x10^-10) (Oddsson et al., Nature Communications 2015, PMID 26272126).
Inheritance
A common variant with a modest effect on risk. ALPL's role in breaking down a natural inhibitor of urinary crystal formation gives this association a direct, plausible biological mechanism rather than only a statistical one.

Kidney stones (nephrolithiasis) form when minerals and salts in urine -- most often calcium combined with oxalate or phosphate -- crystallize into hard deposits in the kidney. They are common, often extremely painful when they pass, and tend to recur once someone has had one; a meaningful share of that recurrence risk is genetic rather than purely dietary.

A whole-genome study of Iceland's own population

The study behind this page took advantage of Iceland's deCODE genetics resource: whole-genome sequencing of 2,636 Icelanders was used to impute 28.3 million sequence variants into a much larger group -- 5,419 kidney stone cases, including 2,172 with a history of recurrent stones, against 279,870 controls. The strongest signal reported was rs1256328, in ALPL (odds ratio 1.21).

ALPL encodes an enzyme that breaks down extracellular inorganic pyrophosphate -- a molecule that normally works specifically to inhibit calcium oxalate and calcium phosphate crystals from forming in urine. A variant that increases ALPL activity would deplete this natural inhibitor faster, which is a biologically direct, plausible mechanism for raising stone risk, not just a statistical association.

Clinical detail

What actually diagnoses and manages this

Kidney stones are diagnosed by imaging (CT or ultrasound) once someone has symptoms, and prevention after a first stone is guided by urine and blood chemistry, not genotype -- adequate fluid intake, and depending on stone type, dietary changes (sodium, oxalate, animal protein) or specific medications. A urologist or nephrologist manages recurrent cases.

One variant, modest effect. An odds ratio of 1.21 is a real but small shift in risk -- hydration and diet remain the interventions with the strongest evidence for preventing kidney stones, regardless of this genotype.

What this page cannot do

  • It cannot diagnose a kidney stone. Imaging does that, typically when someone already has symptoms.
  • It cannot say what type of stone someone is prone to. Stone composition (calcium oxalate, calcium phosphate, uric acid, struvite) is determined by lab analysis of a passed stone or by urine chemistry, not by this variant.
  • It reflects one population. This study was conducted entirely in Iceland; whether the same effect size holds elsewhere was not tested here.

Related variants MyGeneLog™ checks for

What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Kidney Stones comes down to these specific, well-studied positions — not a diagnosis.

Standard

Kidney stones

ALPL · rs1256328

See detailed info →

Sources

Databases, guidelines and references

Papers, with their authors

Quoting this page

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Kidney Stones. MyGeneLog™. https://www.mygenelog.com/conditions/kidney-stones

Questions about Kidney Stones

Does this variant mean I will get a kidney stone?

No. It is a single common variant with a modest effect (odds ratio 1.21) found in one large population study. Hydration and diet remain the interventions with the strongest evidence for prevention.

What does ALPL actually do?

It encodes an enzyme that breaks down a molecule that normally helps prevent calcium crystals from forming in urine. More enzyme activity means less of that natural protection -- a direct, plausible mechanism for the association, not just a statistical one.

How are kidney stones actually diagnosed and prevented?

Diagnosed by imaging once symptoms appear. Prevention after a first stone is guided by urine and blood chemistry -- fluid intake and, depending on stone type, dietary or medical changes -- not by genotype.

Free to reuse. This page's text is original writing from freely-available research, licensed CC BY 4.0 — reuse it, including commercially, with attribution to MyGeneLog™. It's general research-derived information, not medical advice or a diagnosis — see Terms of Use.