Evidence map›Paper›PMID 27153399›Full record

ArticleAmerican journal of human genetics2016

Somatic Mutations in NEK9 Cause Nevus Comedonicus.

Jonathan L Levinsohn, Jeffrey L Sugarman, Yale Center for Mendelian Genomics, Jennifer M McNiff, Richard J Antaya, Keith A Choate

Open access · bronzeAbstract readCase Reports
In one paragraph

Article in American journal of human genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
6.0field-weighted citation impact, top 4% 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

18 citing papers in PubMed, 64 citations in OpenAlex.

  1. The Genetics of Acne.Annals of human genetics · 2025
    Review
  2. Article
  3. Article
  4. Article
  5. Illumination of understudied ciliary kinases.Frontiers in molecular biosciences · 2024
    Review
  6. Article
  7. Review
  8. Article
  9. Novel variants ofFrontiers in genetics · 2022
    Article
  10. Article
  11. Hypertrichotic patches as a mosaic manifestation of Proteus syndrome.Journal of the American Academy of Dermatology · 2021
    Observational
  12. Article
  13. Article
  14. Checking NEKs: Overcoming a Bottleneck in Human Diseases.Molecules (Basel, Switzerland) · 2020
    Review
  15. Article
  16. Article
  17. Review
  18. Mosaicism in Cutaneous Disorders.Annual review of genetics · 2017
    Review
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

6 authors at 2 institutions in 1 country.

Jonathan L LevinsohnDepartment of Genetics, Yale School of Medicine, New Haven, CT 06510, USA; Department of Dermatology, Yale School of Medicine, New Haven, CT 06510, USA.
Jeffrey L SugarmanDepartments of Dermatology and Family Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Yale Center for Mendelian Genomics
Jennifer M McNiffDepartment of Dermatology, Yale School of Medicine, New Haven, CT 06510, USA; Department of Pathology, Yale School of Medicine, New Haven, CT 06510, USA.
Richard J AntayaDepartment of Dermatology, Yale School of Medicine, New Haven, CT 06510, USA; Department of Pediatrics, Yale School of Medicine, New Haven, CT 06510, USA.
Keith A ChoateDepartment of Genetics, Yale School of Medicine, New Haven, CT 06510, USA; Department of Dermatology, Yale School of Medicine, New Haven, CT 06510, USA; Department of Pathology, Yale School of Medicine, New Haven, CT 06510, USA. Electronic address: keith.choate@yale.edu.
Yale University · USUniversity of California, San Francisco · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007205 · NIGMS · YALE UNIVERSITY · PI KAZMIERCZAK, BARBARA I · 1985 to 2019
$42.9M
Yale Center for Mendelian DisordersU54HG006504 · NHGRI · YALE UNIVERSITY · PI GERSTEIN, MARK BENDER, GUNEL, MURAT · 2012 to 2015
$11.0M
NHGRI NIH HHS U54 HG006504NIGMS NIH HHS T32 GM007205
6 · The paper itself

Abstract

Acne vulgaris (AV) affects most adolescents, and of those affected, moderate to severe disease occurs in 20%. Comedones, follicular plugs consisting of desquamated keratinocytes and sebum, are central to its pathogenesis. Despite high heritability in first-degree relatives, AV genetic determinants remain incompletely understood. We therefore employed whole-exome sequencing (WES) in nevus comedonicus (NC), a rare disorder that features comedones and inflammatory acne cysts in localized, linear configurations. WES identified somatic NEK9 mutations, each affecting highly conserved residues within its kinase or RCC1 domains, in affected tissue of three out of three NC-affected subjects. All mutations are gain of function, resulting in increased phosphorylation at Thr210, a hallmark of NEK9 kinase activation. We found that comedo formation in NC is marked by loss of follicular differentiation markers, expansion of keratin-15-positive cells from localization within the bulge to the entire sub-bulge follicle and cyst, and ectopic expression of keratin 10, a marker of interfollicular differentiation not present in normal follicles. These findings suggest that NEK9 mutations in NC disrupt normal follicular differentiation and identify NEK9 as a potential regulator of follicular homeostasis.

Indexed as

AdolescentAdultChildFemaleFluorescent Antibody TechniqueHigh-Throughput Nucleotide SequencingHumansMaleMutationNevusNIMA-Related KinasesPrognosisSkin NeoplasmsYoung AdultNEK9 protein, humanNIMA-Related Kinases

Identifiers

PMID27153399
PMCPMC4863661
OpenAlexW2346248177

What OpenQuestion 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 OpenQuestion graph.