Evidence mapPaperPMID 34890546Full record

ArticleAmerican journal of human genetics2022

Monoallelic IFT140 pathogenic variants are an important cause of the autosomal dominant polycystic kidney-spectrum phenotype.

Sarah R Senum, Ying Sabrina M Li, Katherine A Benson, Giancarlo Joli, Eric Olinger, Sravanthi Lavu, Charles D Madsen, Adriana V Gregory, Ruxandra Neatu, Timothy L Kline and 19 more

Open access · bronzeAbstract read
In one paragraph

Article in American journal of human genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.

0numbers the graph read from it
0cells of the map it votes in
105citing papers in PubMed
16.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

105 citing papers in PubMed, 159 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Review
  6. Monogenic Etiologies of Kidney Cysts in the Pediatric Population: An Observational Cohort Study.Clinical journal of the American Society of Nephrology : CJASN · 2026
    Observational
  7. Article
  8. Article
  9. Article
  10. The Genomic Infinity Loop.Journal of the American Society of Nephrology : JASN · 2026
    Article
  11. Article
  12. Exome Sequencing in a Large Cohort with Ciliopathy-Related Kidney Disease.Clinical journal of the American Society of Nephrology : CJASN · 2026
    Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Typical and atypical ADPKD: predicted pathogenic genetic variants and population frequencies.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2026
    Article
  18. Review
  19. Article
  20. Article

45 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

29 authors at 15 institutions in 8 countries.

Sarah R SenumDivision of Nephrology and Hypertension, Mayo Clinic, Rochester, MN 55905, USA.
Ying Sabrina M LiDivision of Nephrology and Hypertension, Mayo Clinic, Rochester, MN 55905, USA; Department of Nephrology, Chongqing Municipal Hospital of Traditional Chinese Medicine, Chongqing 400021, China.
Katherine A BensonSchool of Pharmacy and Biomolecular Science, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
Giancarlo JoliDivision of Nephrology and Hypertension, Mayo Clinic, Rochester, MN 55905, USA; University Vita Salute San Raffaele, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.
Eric OlingerTranslational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, NE4 5PL, UK.
Sravanthi LavuDivision of Nephrology and Hypertension, Mayo Clinic, Rochester, MN 55905, USA.
Charles D MadsenDivision of Nephrology and Hypertension, Mayo Clinic, Rochester, MN 55905, USA.
Adriana V GregoryDivision of Nephrology and Hypertension, Mayo Clinic, Rochester, MN 55905, USA.
Ruxandra NeatuTranslational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, NE4 5PL, UK.
Timothy L KlineDepartment of Radiology, Mayo Clinic, Rochester, MN 55905, USA.
Marie-Pierre AudrézetUniv Brest, Inserm, UMR 1078, GGB, CHU Brest, F-29200 Brest, France.
Patricia OutedaDivision of Nephrology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Cherie B NauDepartment of Ophthalmology, Mayo Clinic, Rochester, MN 55905, USA.
Esther MeijerDepartment of Nephrology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.
Hamad AliDepartment of Medical Laboratory Sciences, Faculty of Allied Health Sciences, Health Sciences Center, Kuwait University, Sulaibikhat 90805, Kuwait; Department of Genetics and Bioinformatics, Dasman Diabetes Institute (DDI), Dasman 15462, Kuwait.
Theodore I SteinmanRenal Division, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Michal MrugDivision of Nephrology, University of Alabama, Birmingham, AL 35294, USA; The Department of Veterans Affairs Medical Center, Birmingham, AL 35294, USA.
Paul J PhelanRenal Department, NHS Lothian - Royal Infirmary Edinburgh, Edinburgh, EH1 3EG, UK.
Terry J WatnickDivision of Nephrology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Dorien J M PetersDepartment of Human Genetics, Leiden University Medical Center, 2300 RC Leiden, the Netherlands.
Albert C M OngKidney Genetics Group, Academic Nephrology Unit, Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield Medical School, Sheffield, S10 2JF, UK; The Sheffield Kidney Institute, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, S10 2JF, UK.
Peter J ConlonDepartment of Nephrology, Beaumont Hospital and Department of Medicine Royal College of Surgeons in Ireland, Dublin 9, Ireland.
Ronald D PerroneDivision of Nephrology, Tufts Medical Center and Tufts University School of Medicine, Boston, MA 02111, USA.
Emilie Cornec-Le GallUniv Brest, Inserm, UMR 1078, GGB, CHU Brest, F-29200 Brest, France.
Marie C HoganDivision of Nephrology and Hypertension, Mayo Clinic, Rochester, MN 55905, USA.
Vicente E TorresDivision of Nephrology and Hypertension, Mayo Clinic, Rochester, MN 55905, USA.
John A SayerTranslational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, NE4 5PL, UK; Renal Services, Newcastle Upon Tyne Hospitals NHS Foundation Trust, and NIHR Newcastle Biomedical Research Centre, Newcastle University, Newcastle upon Tyne, NE4 5PL, UK.
Genomics England Research Consortium, the HALT PKD, CRISP, DIPAK, ADPKD Modifier, and TAME PKD studies
Peter C HarrisDivision of Nephrology and Hypertension, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: harris.peter@mayo.edu.
Mayo Clinic · USNewcastle University · GBRoyal College of Surgeons in Ireland · IEUniversité de Bretagne Occidentale · FRUniversity of Maryland, Baltimore · USWinnMed · USBeth Israel Deaconess Medical Center · USIstituto di Ricovero e Cura a Carattere Scientifico San RaffaeleKuwait University · KWLeiden University Medical Center · NLRoyal Victoria Hospital · GBTufts University · USUniversity Medical Center Groningen · NLUniversity of Alabama · USUniversity of Sheffield · GB

Funding

Transgenic and Knockout Models of ADPKDR01DK059597 · NIDDK · MAYO CLINIC ROCHESTER · 2002 to 2025
$2.9M
ADPKD:Disease Spectrum &Genotype-Phenotype CorrelationsR01DK058816 · MAYO CLINIC ROCHESTER · 2001 to 2025
$2.2M
PKD Innovation and Resource Development CoreU54DK126114 · UNIVERSITY OF MARYLAND BALTIMORE · 2025 to 2025
$954k
Medical Research Council MC_PC_17228Medical Research Council MC_QA137853NIDDK NIH HHS P30 DK090728NIDDK NIH HHS P30 DK090868NIDDK NIH HHS R01 DK058816NIDDK NIH HHS R01 DK059597NIDDK NIH HHS U54 DK126114
6 · The paper itself

Abstract

Autosomal dominant polycystic kidney disease (ADPKD), characterized by progressive cyst formation/expansion, results in enlarged kidneys and often end stage kidney disease. ADPKD is genetically heterogeneous; PKD1 and PKD2 are the common loci (∼78% and ∼15% of families) and GANAB, DNAJB11, and ALG9 are minor genes. PKD is a ciliary-associated disease, a ciliopathy, and many syndromic ciliopathies have a PKD phenotype. In a multi-cohort/-site collaboration, we screened ADPKD-diagnosed families that were naive to genetic testing (n = 834) or for whom no PKD1 and PKD2 pathogenic variants had been identified (n = 381) with a PKD targeted next-generation sequencing panel (tNGS; n = 1,186) or whole-exome sequencing (WES; n = 29). We identified monoallelic IFT140 loss-of-function (LoF) variants in 12 multiplex families and 26 singletons (1.9% of naive families). IFT140 is a core component of the intraflagellar transport-complex A, responsible for retrograde ciliary trafficking and ciliary entry of membrane proteins; bi-allelic IFT140 variants cause the syndromic ciliopathy, short-rib thoracic dysplasia (SRTD9). The distinctive monoallelic phenotype is mild PKD with large cysts, limited kidney insufficiency, and few liver cysts. Analyses of the cystic kidney disease probands of Genomics England 100K showed that 2.1% had IFT140 LoF variants. Analysis of the UK Biobank cystic kidney disease group showed probands with IFT140 LoF variants as the third most common group, after PKD1 and PKD2. The proximity of IFT140 to PKD1 (∼0.5 Mb) in 16p13.3 can cause diagnostic confusion, and PKD1 variants could modify the IFT140 phenotype. Importantly, our studies link a ciliary structural protein to the ADPKD spectrum.

Indexed as

AllelesCarrier ProteinsGenetic Predisposition to DiseaseMutationAdultAgedAmino Acid SubstitutionBiological Specimen BanksCiliaDNA Copy Number VariationsExome SequencingFemaleGenetic Association StudiesGenetic TestingHigh-Throughput Nucleotide SequencingHumansCarrier ProteinsIFT140 protein, humanADPKDciliaciliopathyIFT140intraflagellar transportmonoallelic cystic diseasepolycystic kidney diseaseshort rib thoracic dysplasia

Identifiers

PMID34890546
PMCPMC8764120
OpenAlexW4200009634

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.