Evidence map›Paper›PMID 26197705›Full record

ArticlePigment cell & melanoma research2015

Identification and functional characterization of natural human melanocortin 1 receptor mutant alleles in Pakistani population.

Mohsin Shahzad, Julia Sires Campos, Nabeela Tariq, Cecilia Herraiz Serrano, Rizwan Yousaf, Celia Jiménez-Cervantes, Sairah Yousaf, Yar M Waryah, Haseeb A Dad, Elizabeth M Blue and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Pigment cell & melanoma research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.6field-weighted citation impact, top 33% 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

2 citing papers in PubMed, 6 citations in OpenAlex.

  1. Trial
  2. Article
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

20 authors at 9 institutions in 3 countries.

Mohsin ShahzadDepartment of Otorhinolaryngology Head and Neck Surgery, School of Medicine, University of Maryland, Baltimore, MD, USA.
Julia Sires CamposDepartment of Biochemistry and Molecular Biology, School of Medicine, University of Murcia and IMIB-Arrixaca, Murcia, Spain.
Nabeela TariqInstitute of Molecular Biology & Biotechnology, Bahauddin Zakariya University, Multan, Pakistan.
Cecilia Herraiz SerranoDepartment of Biochemistry and Molecular Biology, School of Medicine, University of Murcia and IMIB-Arrixaca, Murcia, Spain.
Rizwan YousafDepartment of Otorhinolaryngology Head and Neck Surgery, School of Medicine, University of Maryland, Baltimore, MD, USA.
Celia Jiménez-CervantesDepartment of Biochemistry and Molecular Biology, School of Medicine, University of Murcia and IMIB-Arrixaca, Murcia, Spain.
Sairah YousafDepartment of Otorhinolaryngology Head and Neck Surgery, School of Medicine, University of Maryland, Baltimore, MD, USA.
Yar M WaryahMolecular Biology & Genetics Department, Medical Research Center, Liaquat University of Medical & Health Sciences, Jamshoro, Pakistan.
Haseeb A DadInstitute of Pharmaceutical Sciences, University of Veterinary & Animal Sciences, Lahore, Pakistan.
Elizabeth M BlueDivision of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA, USA.
Nara SobreiraMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Francesc López-GiráldezYale Center for Genome Analysis, Yale University, West Haven, CT, USA.
University of Washington Center for Mendelian Genomics
Tasleem KausarInstitute of Molecular Biology & Biotechnology, Bahauddin Zakariya University, Multan, Pakistan.
Muhammad AliInstitute of Molecular Biology & Biotechnology, Bahauddin Zakariya University, Multan, Pakistan.
Ali M WaryahMolecular Biology & Genetics Department, Medical Research Center, Liaquat University of Medical & Health Sciences, Jamshoro, Pakistan.
Saima RiazuddinDepartment of Otorhinolaryngology Head and Neck Surgery, School of Medicine, University of Maryland, Baltimore, MD, USA.
Rehan S ShaikhInstitute of Molecular Biology & Biotechnology, Bahauddin Zakariya University, Multan, Pakistan.
José C García-BorrónDepartment of Biochemistry and Molecular Biology, School of Medicine, University of Murcia and IMIB-Arrixaca, Murcia, Spain.
Zubair M AhmedDepartment of Otorhinolaryngology Head and Neck Surgery, School of Medicine, University of Maryland, Baltimore, MD, USA.
University of Maryland, Baltimore · USBahauddin Zakariya University · PKUniversidad de Murcia · ESLiaquat University of Medical & Health Sciences · PKInstituto Murciano de Investigación Biosanitaria · ESJohns Hopkins Medicine · USUniversity of Veterinary and Animal Sciences · PKUniversity of Washington Medical Center · USYale University · US

Funding

UW Center for Mendelian GenomicsU54HG006493 · NHGRI · UNIVERSITY OF WASHINGTON · PI BAMSHAD, MICHAEL JOSEPH, NICKERSON, DEBORAH A · 2012 to 2015
$20.0M
Baylor-Johns Hopkins Center for Mendelian GeneticsU54HG006542 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 2012 to 2015
$15.6M
UW Center for Mendelian GenomicsUM1HG006493 · NHGRI · UNIVERSITY OF WASHINGTON · PI BAMSHAD, MICHAEL JOSEPH, LEAL, SUZANNE M · 2016 to 2020
$15.3M
Yale Center for Mendelian GenomicsUM1HG006504 · NHGRI · YALE UNIVERSITY · PI GERSTEIN, MARK BENDER, GUNEL, MURAT · 2016 to 2020
$14.8M
Baylor-Johns Hopkins Center for Mendelian GeneticsUM1HG006542 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 2016 to 2020
$14.5M
Yale Center for Mendelian DisordersU54HG006504 · NHGRI · YALE UNIVERSITY · PI GERSTEIN, MARK BENDER, GUNEL, MURAT · 2012 to 2015
$11.0M
Identifying Genes for Non-syndromic Recessive Deafness-A Collaborative StudyR01DC011803 · NIDCD · UNIVERSITY OF MARYLAND BALTIMORE · PI RIAZUDDIN, SAIMA · 2012 to 2016
$1.6M
Molecular Genetics of nonsyndromic Oculocutaneous AlbinismR56AR065483 · NIAMS · UNIVERSITY OF MARYLAND BALTIMORE · PI AHMED, ZUBAIR M. · 2014 to 2015
$666k
NHGRI NIH HHS U54 HG006493NHGRI NIH HHS U54 HG006504NHGRI NIH HHS U54 HG006542NHGRI NIH HHS UM1 HG006493NHGRI NIH HHS UM1 HG006504NHGRI NIH HHS UM1 HG006542NIAMS NIH HHS R56 AR065483NIDCD NIH HHS R01 DC011803
6 · The paper itself

Abstract

Melanocortin 1 receptor (MC1R), a Gs protein-coupled receptor of the melanocyte's plasma membrane, is a major determinant of skin pigmentation and phototype. Upon activation by α-melanocyte stimulating hormone, MC1R triggers the cAMP cascade to stimulate eumelanogenesis. We used whole-exome sequencing to identify causative alleles in Pakistani families with skin and hair hypopigmentation. Six MC1R mutations segregated with the phenotype in seven families, including a p.Val174del in-frame deletion and a p.Tyr298* nonsense mutation, that were analyzed for function in heterologous HEK293 cells. p.Tyr298* MC1R showed no agonist-induced signaling to the cAMP or ERK pathways, nor detectable agonist binding. Conversely, signaling was comparable for p.Val174del and wild-type in HEK cells overexpressing the proteins, but binding analysis suggested impaired cell surface expression. Flow cytometry and confocal imaging studies revealed reduced plasma membrane expression of p.Val174del and p.Tyr298*. Therefore, p.Tyr298* was a total loss-of-function (LOF) allele, while p.Val174del displayed a partial LOF attribute.

Indexed as

AllelesFamilyFemaleHumansHypopigmentationMaleMutationPakistanPedigreePhenotypeReceptor, Melanocortin, Type 1Receptor, Melanocortin, Type 1cAMP signalinghypopigmentationmelanocortin 1 receptormelanocytes

Identifiers

PMID26197705
PMCPMC4609612
OpenAlexW1770652915

What OpenQuestion holds

Textmetadata
LicenceTDM
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.