GM17236

GM17236 LCL from B-Lymphocyte

Description:

HUMAN VARIATION PANEL - WHITE PANEL OF 50
HUMAN VARIATION PANEL - WHITE PANEL OF 100 (SET 1)
HUMAN VARIATION PANEL - WHITE PANEL OF 200
CYTOCHROME P450, SUBFAMILY IID, POLYPEPTIDE 6; CYP2D6

Affected:

No

Sex:

Female

Age:

26 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Human Variation
Pharmacogenetics
GeT-RM Samples
dbGaP

Alternate IDs

GM10959 [HUMAN VARIATION PANEL - WHITE PANEL OF 50]

Biopsy Source

Peripheral vein

Cell Type

B-Lymphocyte

Tissue Type

Blood

Transformant

Epstein-Barr Virus

Sample Source

LCL from B-Lymphocyte

Species

Homo sapiens

Common Name

Human

Remarks

Donor subject is a compound heterozygote: one allele carries a variant CYP2D6 gene (CYP2D6*2) which contains two amino acid substitutions: a C>T transition at nucleotide 2938 in exon 6 resulting in an arg296-to-cys [Arg296Cys (R296C)] and a G>C transversion at nucleotide 4268 in exon 9 resulting in a ser486-to-thr [Ser486Thr (S486T)]; a second allele carries a C>T change at nucleotide 2850

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by Nucleoside Phosphorylase,Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis

Pharmacogenomics Panel

For pharmacogenetic variants please click here: GeT-RM PGx Search

Gene

CYP2D6

Chromosomal Location

22q13.1

Allelic Variant 1

124030.0007; DEBRISOQUINE, ULTRARAPID METABOLISM OF

Identified Mutation

ARG296CYS AND SER486THR; This allelic variant is also known as CYP2D6*2 or CYP2D6L. In a family in which 2 sibs and their father had MRs of less that 0.02 (ultrarapid phenotype, see 608902), Johansson et al. (Proc Nat Acad Sci 90:11825-11829, 1993) found 12 extra copies of the CYP2D6 gene inherited in an autosomal dominant pattern; in a second family in which 2 sibs had MRs of less than 0.1, the authors found 2 extra copies of the CYP2D6 gene. All affected individuals had a variant CYP2D6 gene, termed CYP2D6L, which contained 2 amino acid substitutions: a 2938C-T transition in exon 6, resulting in an arg296-to-cys (R296C), and a 4268G-to-C transversion in exon 9, resulting in a resulting in a ser486-to-thr (S486T) substitution. The MR of individuals with 1 copy of the CYP2D6L gene did not differ from those with the wildtype gene, but there was a correlation between decreased MR and increased copies of the CYP2D6L gene.

Gene

CYP2D6

Chromosomal Location

22q13.1

Allelic Variant 2

; DEBRISOQUINE, NORMAL METABOLISM OF

Identified Mutation

2850C>T

Phenotypic Data

Remarks

Publications

Pratt VM, Turner A, Broeckel U, Dawson DB, Gaedigk A, Lynnes TC, Medeiros EB, Moyer AM, Requesens D, Ventrini F, Kalman LV, Characterization of Reference Materials for CYP2C9, CYP2C19, VKORC1, CYP2C Cluster Variant, GGCX, and Other Pharmacogenetic Alleles with an Association for Molecular Pathology (AMP) Pharmacogenetics Working Group Tier 2 Status - A GeT-RM Collaborative Project The Journal of molecular diagnostics : JMD: 2021

PubMed ID: 34020041

Kwon YL, Kim BM, Lee EY, Shin KJ, Massively parallel sequencing of 25 autosomal STRs including SE33 in four population groups for forensic applications Scientific reports11:4701 2020

PubMed ID: 33633141

Wang G, Qin S, Zayas J, Ingle JN, Liu M, Weinshilboum RM, Shen K, Wang L, 4-Hydroxytamoxifen enhances sensitivity of estrogen receptor a-positive breast cancer to docetaxel in an estrogen and ZNF423 SNP-dependent fashion Breast cancer research and treatment175:567-578 2018

PubMed ID: 30937657

Pratt VM, Zehnbauer B, Wilson JA, Baak R, Babic N, Bettinotti M, Buller A, Butz K, Campbell M, Civalier C, El-Badry A, Farkas DH, Lyon E, Mandal S, McKinney J, Muralidharan K, Noll L, Sander T, Shabbeer J, Smith C, Telatar M, Toji L, Vairavan A, Vance C, Weck KE, Wu AH, Yeo KT, Zeller M, and Kalman L., Characterization of 107 Genomic DNA Reference Materials for CYP2D6, CYP2C19, CYP2C9, VKORC1, and UGT1A1 J Mol Diagn12(6):835-46 2010

PubMed ID: 20889555

Li L, Fridley B, Kalari K, Jenkins G, Batzler A, Safgren S, Hildebrandt M, Ames M, Schaid D, Wang L, Gemcitabine and Cytosine Arabinoside Cytotoxicity: Association with Lymphoblastoid Cell Expression Cancer research68:7050-7058 2008

PubMed ID: 18757419

Marini NJ, Gin J, Ziegle J, Keho KH, Ginzinger D, Gilbert DA, Rine J, The prevalence of folate-remedial MTHFR enzyme variants in humans Proceedings of the National Academy of Sciences of the United States of America68:7050-7058 2008

PubMed ID: 18523009

Atwal GS, Bond GL, Metsuyanim S, Papa M, Friedman E, Distelman-Menachem T, Ben Asher E, Lancet D, Ross DA, Sninsky J, White TJ, Levine AJ, Yarden R, Haplotype structure and selection of the MDM2 oncogene in humans Proceedings of the National Academy of Sciences of the United States of America104:4524-9 2007

PubMed ID: 17360557

Gonzalez-Covarrubias V, Ghosh D, Lakhman SS, Pendyala L, Blanco JG, A functional genetic polymorphism on human carbonyl reductase 1 (CBR1 V88I) impacts on catalytic activity and NADPH binding affinity Drug metabolism and disposition: the biological fate of chemicals35:973-80 2007

PubMed ID: 17344335

Melis, R., Lyon, E., and McMillin, G.A., Determination of CYP2D6, CYP2C9 and CYP2C19 genotypes with Tag-It mutation detection assays Expert Rev Mol Diagn6(6):811-20 2006

PubMed ID: 17140368

Mukherjee B, Salavaggione OE, Pelleymounter LL, Moon I, Eckloff BW, Schaid DJ, Wieben ED, Weinshilboum RM, Glutathione S-transferase omega 1 and omega 2 pharmacogenomics Drug metabolism and disposition: the biological fate of chemicals34:1237-46 2006

PubMed ID: 16638819

Chen HJ, Tian H, Edenberg HJ, Natural haplotypes in the regulatory sequences affect human alcohol dehydrogenase 1C (ADH1C) gene expression Human mutation25:150-5 2005

PubMed ID: 15643610

Dib-Hajj SD, Rush AM, Cummins TR, Hisama FM, Novella S, Tyrrell L, Marshall L, Waxman SG, Gain-of-function mutation in Nav17 in familial erythromelalgia induces bursting of sensory neurons Brain : a journal of neurology128:1847-54 2005

PubMed ID: 15958509

Dick DM, Edenberg HJ, Xuei X, Goate A, Hesselbrock V, Schuckit M, Crowe R, Foroud T, No association of the GABAA receptor genes on chromosome 5 with alcoholism in the collaborative study on the genetics of alcoholism sample American journal of medical genetics Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics132:24-8 2005

PubMed ID: 15690551

Harris SL, Gil G, Robins H, Hu W, Hirshfield K, Bond E, Bond G, Levine AJ, Detection of functional single-nucleotide polymorphisms that affect apoptosis Proceedings of the National Academy of Sciences of the United States of America102:16297-302 2005

PubMed ID: 16260726

Maitland ML, Grimsley C, Kuttab-Boulos H, Witonsky D, Kasza KE, Yang L, Roe BA, Di Rienzo A, Comparative genomics analysis of human sequence variation in the UGT1A gene cluster The pharmacogenomics journal6:52-62 2005

PubMed ID: 16314881

Ulrich CM, Carlson CS, Sibert J, Poole EM, Yu JH, Wang LH, Sparks R, Potter JD, Bigler J, Thromboxane synthase (TBXAS1) polymorphisms in African-American and Caucasian populations: evidence for selective pressure Human mutation26:394-5 2005

PubMed ID: 16134166

Thompson EE, Kuttab-Boulos H, Witonsky D, Yang L, Roe BA, Di Rienzo A, CYP3A variation and the evolution of salt-sensitivity variants. Am J Hum Genet75(6):1059-69 2004

PubMed ID: 15492926