Two numbers describe most of what a kidney is doing: how fast it filters, and how much albumin leaks into urine. Both are heritable. One of the genes here raises the albumin number without harming the kidney at all, and the albumin number and blood pressure turn out to drive each other in both directions.
What this condition connects to
Solid lines are connections this site curates. Dashed lines mean the two ends share a research paper — worth knowing, and not a claim that one explains the other.
Prevalence
A meta-analysis of estimated glomerular filtration rate combined 133,413 individuals with replication in up to 42,166, identifying 24 new and confirming 29 known loci — 53 in total, 19 of which also associated with filtration rate among people with diabetes (Pattaro et al., Nature Communications 2016, PMID 26831199). A genome-wide study of albuminuria in 382,500 individuals identified 32 new loci (Haas et al., American Journal of Human Genetics 2018, PMID 30220432). A trans-ethnic analysis of 71,638 individuals across four ancestries identified 20 loci and found allelic effects at the lead variants homogeneous across ancestries (Mahajan et al., American Journal of Human Genetics 2016, PMID 27588450).
Inheritance
Common variants, each shifting a filtration or albumin measurement slightly. Distinct from the inherited kidney diseases — polycystic kidney disease, Alport syndrome — which are caused by rare changes in single genes and are diagnosed directly rather than through a common-variant catalogue.
Kidney function is usually reported as two numbers. Estimated glomerular filtration rate says how fast blood is being filtered, calculated from creatinine in blood. Urinary albumin says how much protein is leaking through into urine. A low filtration rate or a high albumin level is what defines chronic kidney disease.
How much of these numbers is inherited
A 2016 meta-analysis of filtration rate combined 133,413 people with replication in up to 42,166 more, identifying 24 new loci and confirming 29 already known — 53 in all. Nineteen of them also associated with filtration rate among people who had diabetes.
A 2018 study of 382,500 people did the same for albuminuria and found 32 new loci.
A rare thing on this site: a finding that runs both ways
Most of what genetics has to say about a routine measurement is deflating — the number marks risk without causing it, as with HDL cholesterol and several of the blood cell indices. Albuminuria is the exception.
The 2018 study tested causality in both directions using variants as natural experiments. Genetically raised albuminuria led to higher blood pressure — about 2.16 mmHg of systolic pressure per standard deviation of predicted albuminuria. And genetically raised blood pressure led to more albuminuria. Each pushes the other.
That makes albuminuria and blood pressure two ends of one loop rather than a cause and its marker, and it is why a raised albumin result is taken seriously by doctors even when the filtration rate still looks fine.
And one gene that moves the test, not the kidney
CUBN encodes cubilin, a receptor in the proximal tubule whose job is to pull albumin back out of the filtrate before it leaves as urine. When that reabsorption step works less efficiently, more albumin appears in the sample.
The kidney is not being damaged. The measurement is moving, and the measurement is the one used to detect kidney damage. This site holds two CUBN variants filed under urinary albumin excretion, and they are the clearest example in the whole catalogue of a genotype changing a number rather than a condition.
Clinical detail
The genes worth knowing by name
UMOD — uromodulin, the most abundant protein in normal urine and the strongest common signal for filtration rate. It is made only in the kidney, which is unusual and is part of why the association is believed to be real rather than a reflection of something else.
SHROOM3 — associated with filtration rate and with chronic kidney disease itself, not only with the measurement.
CUBN — albumin reabsorption, described above.
WDR72 and SLC34A1 — both appear across creatinine and urea measures.
A caveat this page does not need to make
Most pages here carry a warning that the evidence was gathered mostly in people of European ancestry. For filtration rate, one study is a partial exception worth stating: an analysis of 71,638 people across four ancestry groups found that the allelic effects at the lead variants were homogeneous across ancestries. The effect sizes travelled, which is not something that can be assumed and is not always what is found.
That is about the variants, not about the equation. Estimated filtration rate is calculated from creatinine using a formula, and how those formulas should handle ancestry has been argued over and revised in clinical practice — a separate question from the genetics, and one settled by kidney societies rather than by this page.
What this page cannot do
It cannot tell you your kidney function. A blood test and a urine test do, cheaply, and they capture everything genetics cannot see — blood pressure, diabetes, medicines, dehydration, infection.
It cannot diagnose chronic kidney disease. That is a filtration rate or an albumin level, measured, and sustained over months.
It cannot explain an abnormal result. Except in one narrow and interesting sense: a persistently raised albumin result with no other sign of kidney disease is exactly the pattern CUBN can produce. That is a conversation for a doctor, not a conclusion to draw here.
Related variants MyGeneLog checks for
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Kidney Function comes down to these specific, well-studied positions — not a diagnosis. 66 positions are linked to this page; the ones this page's own text discusses are shown first.
Journal of the American Society of Nephrology : JASN · 2011 · PMID 21355061
Frequently asked questions
Can a DNA test tell me how well my kidneys work?
No. A blood creatinine test and a urine albumin test do, they cost very little, and they capture everything genetics cannot see — blood pressure, diabetes, medicines, dehydration and infection. The variants here shift averages.
My urine albumin came back high. Could that be genetic?
It can be, in one specific and interesting way. CUBN encodes the receptor that reabsorbs albumin before urine leaves the kidney, and variation in it raises measured albumin without the kidney being damaged. That is a pattern for a doctor to consider, not a conclusion to draw from a website — a raised albumin result usually does mean something and is taken seriously.
Does albuminuria cause high blood pressure, or the other way round?
Both, according to a study that tested each direction separately using genetic variants as natural experiments. Genetically raised albuminuria led to higher blood pressure, and genetically raised blood pressure led to more albuminuria. They form a loop, which is why a raised albumin result matters even when filtration still looks normal.
Is this evidence only from people of European ancestry?
Largely, as on most of this site, but with a real exception here. An analysis across four ancestry groups in 71,638 people found the effects at the lead filtration-rate variants were similar across them. That is a stronger result than usual and it is worth saying so.
Do these variants mean I will get kidney disease?
No. Chronic kidney disease is defined by measured filtration rate or albumin sustained over months, and the inherited kidney diseases that do come close to deciding an outcome — polycystic kidney disease, Alport syndrome — are caused by rare changes this catalogue does not carry.
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.