ANKK1

Last updated
ANKK1
Identifiers
Aliases ANKK1 , PKK2, ankyrin repeat and kinase domain containing 1, DRD2, sgK288
External IDs OMIM: 608774 MGI: 3045301 HomoloGene: 18258 GeneCards: ANKK1
Orthologs
SpeciesHumanMouse
Entrez

255239

244859

Ensembl

ENSG00000170209

ENSMUSG00000032257

UniProt

Q8NFD2

Q8BZ25

RefSeq (mRNA)

NM_178510

NM_172922
NM_001376951

RefSeq (protein)

NP_848605

NP_766510
NP_001363880

Location (UCSC) Chr 11: 113.39 – 113.4 Mb Chr 9: 49.33 – 49.34 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Ankyrin repeat and kinase domain containing 1 (ANKK1) also known as protein kinase PKK2 or sugen kinase 288 (SgK288) is an enzyme that in humans is encoded by the ANKK1 gene. The ANKK1 is a member of an extensive family of the Ser/Thr protein kinase family, and protein kinase superfamily involved in signal transduction pathways.

Contents

Clinical significance

This gene contains a single nucleotide polymorphism that causes an amino acid substitution within the 11th of 12 ankyrin repeats of ANKK1 (Glu713Lys of 765 residues). This polymorphism, which is commonly referred to Taq1A, was previously believed to be located in the promoter region of the DRD2 gene, since the polymorphism is proximal to the DRD2 gene and can influence DRD2 receptor expression. [5] It is now known to be located in the coding region of the ANKK1 gene which controls the synthesis of dopamine in the brain. [6] The A1 allele is associated with increased activity of striatal L-amino acid decarboxylase. [7]

A1+ allele

Given that the A1+ allele is associated with antisocial personality disorder, one may infer that the allele is also associated with narcissistic personality disorder and histrionic personality disorder. However, these predictions have not yet been empirically verified.

A1+ genotype frequencies

European population estimates for A1+ genotype frequencies range from 20.8 to 43.4% (National Center of Biotechnology Information (NCBI), identification number rs1800497). [12]

Addictive behaviors

The ANKK1 gene is closely linked to dopamine receptor D2 (DRD2) on chromosome band 11q23.1. [13] The A1 allele of the Taq1A polymorphism (rs1800497T), is located ≈10kb downstream of the dopamine receptor DRD2 gene. Dopamine (DA) is a neurotransmitter in the brain, which controls feelings of wellbeing. This sensation results from the interaction of dopamine and other neurotransmitters such as serotonin, the opioids, and other brain chemicals. Dopamine increases the motivation for food cravings and appetite mediation. [14]

The Reward Deficiency Syndrome (RDS) involves the pleasures or reward mechanisms that rely on dopamine. The result of this deficiency is based on the genetic makeup; this helps explain how certain simple genetic anomalies can give rise to complex aberrant behaviours as the ones mentioned previously. The A1 allelic prevalence has been reported to be significantly higher in obese individuals than in lean subjects, [15] moreover, individuals with increased body mass index (BMI) (BMI ≥ 30 kg/m2) have fewer DRD2 dopamine receptors. Investigators have also suggested that hormonal mechanism may underline a gender difference in the ability to suppress hunger in relation to this SNP, which may contribute to the greater incidence of obesity in women compared to men. [16] However, authors have pointed out that A1 carriers have difficulty in learning from negative feedback in a reinforcement-learning task and are less efficient at learning to avoid actions that have negative consequences.

Related Research Articles

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<span class="mw-page-title-main">Dopamine receptor</span> Class of G protein-coupled receptors

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<span class="mw-page-title-main">Dopamine transporter</span> Mammalian protein found in Homo sapiens

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<span class="mw-page-title-main">Growth hormone secretagogue receptor</span> Protein-coding gene in the species Homo sapiens

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Dopamine receptor D<sub>2</sub> Main receptor for most antipsychotic drugs

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Dopamine receptor D<sub>1</sub> Protein-coding gene in the species Homo sapiens

Dopamine receptor D1, also known as DRD1. It is one of the two types of D1-like receptor family - receptors D1 and D5. It is a protein that in humans is encoded by the DRD1 gene.

Dopamine receptor D<sub>5</sub> Protein-coding gene in the species Homo sapiens

Dopamine receptor D5, also known as D1BR, is a protein that in humans is encoded by the DRD5 gene. It belongs to the D1-like receptor family along with the D1 receptor subtype.

Dopamine receptor D<sub>3</sub> Subtype of the dopamine receptor protein

Dopamine receptor D3 is a protein that in humans is encoded by the DRD3 gene.

<span class="mw-page-title-main">GRK4</span> Protein-coding gene in the species Homo sapiens

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rs6295, also called C(-1019)G, is a gene variation—a single nucleotide polymorphism (SNP)—in the HTR1A gene. It is one of the most investigated SNPs of its gene. The C-allele is the most prevalent with 0.675 against the G-allele with 0.325 among Caucasian.

<span class="mw-page-title-main">HTR3B</span>

5-hydroxytryptamine (serotonin) receptor 3B, also known as HTR3B, is a human gene. The protein encoded by this gene is a subunit of the 5-HT3 receptor.

In genetics, rs1800955 is a single nucleotide polymorphism (SNP). It is located in the promoter region of the DRD4 gene. This gene codes for the dopamine receptor D4.

In Cloninger's model of psychobiology, novelty seeking (NS) is an inherited, unlearned, temperamental bias toward novel signals from the environment. It can be measured along a spectrum from low to high and when toward the upper end of the spectrum, it is associated with higher exploratory activity, need for higher levels of baseline stimulation, impulsive decision making, extravagance in approach to reward cues, quick temperedness, low tolerance for frustration, impulsivity, and proneness to addiction. It is measured in the Tridimensional Personality Questionnaire as well as the later version Temperament and Character Inventory and is considered one of the temperament dimensions of personality. Like the other temperament dimensions, it has been found to be highly heritable. High NS has been suggested to be related to low dopaminergic activity.

The relationship between schizoid personality disorder (SPD) and avoidant personality disorder (AvPD) has been a subject of controversy for decades.

The C957T gene polymorphism is a synonymous mutation located within the 957th base pair of the DRD2 gene. This base pair is located in exon 7. Most synonymous mutations are silent. However, the C957T mutation is an exception to this rule. While the 957C allele codes for the same polypeptide as the 957T allele, the conformation of 957T messenger RNA differs from the conformation of 957C messenger RNA. 957T messenger RNA is less stable and more prone to degradation. As a result, dopamine D2 receptor expression is decreased among individuals who carry the 957T allele compared to individuals who carry the 957C allele.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000170209 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000032257 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Lucht M, Rosskopf D (July 2008). "Comment on "Genetically determined differences in learning from errors"". Science. 321 (5886): 200, author reply 200. Bibcode:2008Sci...321..200L. doi: 10.1126/science.1155372 . PMID   18621654.
  6. ↑ Neville MJ, Johnstone EC, Walton RT (June 2004). "Identification and characterization of ANKK1: a novel kinase gene closely linked to DRD2 on chromosome band 11q23.1". Hum. Mutat. 23 (6): 540–5. doi: 10.1002/humu.20039 . PMID   15146457. S2CID   22242611.
  7. ↑ Laakso A, Pohjalainen T, Bergman J, Kajander J, Haaparanta M, Solin O, Syvälahti E, Hietala J (June 2005). "The A1 allele of the human D2 dopamine receptor gene is associated with increased activity of striatal L-amino acid decarboxylase in healthy subjects". Pharmacogenet. Genomics. 15 (6): 387–91. doi:10.1097/01213011-200506000-00003. PMID   15900211. S2CID   25424974.
  8. ↑ Lawford B, Young R, Noble EP, Crawford D, Rowell J, Shadforth S, Ritchie T, Zhang X, Cooksley GE (January 1999). "The DRD2A1allele: a behavioural genetic risk factor in hepatitis C infection of persistent drug abusers". Addict Biol. 4 (1): 61–6. doi:10.1080/13556219971858. PMID   20575771. S2CID   5493559.
  9. ↑ Lu RB, Lee JF, Huang SY, Lee SY, Chang YH, Kuo PH, Chen SL, Chen SH, Chu CH, Lin WW, Wu PL, Ko HC (November 2010). "Interaction between ALDH2*1*1 and DRD2/ANKK1 TaqI A1A1 genes may be associated with antisocial personality disorder not co-morbid with alcoholism". Addict Biol. 17 (5): 865–874. doi:10.1111/j.1369-1600.2010.00268.x. PMID   21070510. S2CID   205400719.
  10. ↑ Ponce G, Hoenicka J, Jiménez-Arriero MA, Rodríguez-Jiménez R, Aragüés M, Martín-Suñé N, Huertas E, Palomo T (August 2008). "DRD2 and ANKK1 genotype in alcohol-dependent patients with psychopathic traits: association and interaction study". Br J Psychiatry. 193 (2): 121–5. doi: 10.1192/bjp.bp.107.041582 . PMID   18669994.
  11. ↑ Blum K, Braverman ER, Wu S, Cull JG, Chen TJ, Gill J, Wood R, Eisenberg A, Sherman M, Davis KR, Matthews D, Fischer L, Schnautz N, Walsh W, Pontius AA, Zedar M, Kaats G, Comings DE (May 1997). "Association of polymorphisms of dopamine D2 receptor (DRD2), and dopamine transporter (DAT1) genes with schizoid/avoidant behaviors (SAB)". Mol. Psychiatry. 2 (3): 239–46. doi: 10.1038/sj.mp.4000261 . PMID   9152988.
  12. ↑ "rs1800497". Reference SNP(refSNP) Cluster Report. United States National Center for Biotechnology Information.
  13. ↑ Neville MJ, Johnstone EC, Walton RT (22 April 2004). "Identification and characterization of ANKK1: A novel kinase gene closely linked to DRD2 on chromosome band 11q23.1". Human Mutation. 23 (6): 540–545. doi: 10.1002/humu.20039 . PMID   15146457. S2CID   22242611.
  14. ↑ Stice E, Spoor S, Bohon C, Small DM (17 October 2008). "Relation Between Obesity and Blunted Striatal Response to Food Is Moderated by TaqIA A1 Allele". Science . 322 (5900): 449–452. Bibcode:2008Sci...322..449S. doi:10.1126/science.1161550. PMC   2681095 . PMID   18927395.
  15. ↑ Ariza M, Garolera M, Jurado MA, Garcia-Garcia I, Hernan I, Sánchez-Garre C, Vernet-Vernet M, Sender-Palacios MJ, Marques-Iturria I, Pueyo R, Segura B, Narberhaus A (25 July 2012). "Dopamine Genes (DRD2/ANKK1-TaqA1 and DRD4-7R) and Executive Function: Their Interaction with Obesity". PLOS ONE. 7 (7): e41482. Bibcode:2012PLoSO...741482A. doi: 10.1371/journal.pone.0041482 . PMC   3405092 . PMID   22848508.
  16. ↑ Heber D, Carpenter CL (19 April 2011). "Addictive Genes and the Relationship to Obesity and Inflammation". Molecular Neurobiology. 44 (2): 160–165. doi:10.1007/s12035-011-8180-6. PMC   3180592 . PMID   21499988.
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