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α1

Structural Information
Species TM AA Chromosomal Location Gene Name Reference
Human 4 449 5q32 GLRA1 18
Rat 4 457 10q22 Glra1 19
Mouse 4 457 11 B1.3 Glra1 17
Contents:
Structural Information
Database Links
Tissue Distribution
Physiological Consequences of Altering Gene Expression
Clinically-Relevant Mutations
Subunit Comments
Database Links
ChEMBL Target 102688 (Hs), 12235 (Rn)
Ensembl ENSG00000145888 (Hs), ENSMUSG00000000263 (Mm), ENSRNOG00000013588 (Rn)
Entrez Gene 2741 (Hs), 14654 (Mm), 25674 (Rn)
GeneCards GLRA1 (Hs)
HomoloGene 20083 (Hs)
OMIM 138491 (Hs)
PharmGKB Gene PA28727 (Hs)
RefSeq Nucleotide NM_000171 (Hs), NM_020492 (Mm), NM_013133 (Rn)
RefSeq Protein NP_000162 (Hs), NP_065238 (Mm), NP_037265 (Rn)
UniGene Hs. 121490 (Hs)
UniProt P23415 (Hs), Q64018 (Mm), P07727 (Rn)
Wikipedia α1
Search for 3D structures on the PDB
Search using keywords: Glycine receptors alpha1 Search using accession numbers: Q64018 || P07727 || P23415
Tissue Distribution
Spinal cord, trigeminal nuclei, superior olive nucleus, nuclei of lateral lemniscus, vestibular nuclei, cuneate nucleus, gracile nucleus, hypoglossal nucleus, dorsal motor nucleus of vagus, superior colliculus.
Species:  Rat
Technique:  Strychnine Autoradiography (does not distinguish among α GlyR subtypes)
References:  30
Spinal cord, trigeminal nuclei, superior olive nucleus, nuclei of lateral lemniscus, vestibular nuclei, cuneate nucleus, gracile nucleus, hypoglossal nucleus, dorsal motor nucleus of vagus, superior colliculus
Species:  Human
Technique:  Strychnine Autoradiography (does not distinguish among α GlyR subtypes)
References:  31
Cochlear nuclei, trigeminal motor nucleus, parabrachial area, lateral reticular nucleus, dorsal nucleus of the lateral lemniscus, cerebellar nuclei, trigeminal spinal nucleus, anterior horn and reticular formation, cerebellum.
Species:  Rat
Technique:  Immunocytochemistry (does not distinguish among α GlyR subtypes)
References:  32
Spinal cord, olfactory bulb, cerebellum, hippocampus.
Species:  Rat
Technique:  Immunocytochemistry (does not distinguish among α GlyR subtypes)
References:  33
Spinal cord, superior and inferior colliculi, hypothalamus, parafascicular nucleus, brain stem nuclei.
Species:  Rat
Technique:  In situ hybridisation
References:  34
Cranial nuclei, sensory nuclei such as the spinal trigeminal nucleus, principal trigeminal nucleus, gracile and cuneate nuclei, dorsal and ventral cochlear nuclei, superior olivary nucleus, medial and lateral trapezoid nuclei, lateral lemniscus and vestibular nuclei, red nucleus, parabrachial area, cerebellar nuclei, dorsal tegmental nucleus, reticular formation, parafascicular nucleus.
Species:  Rat
Technique:  In situ hybridisation
References:  35
Retina (bipolar cells, subset of ganglion cells in inner nuclear layer)
Species:  Rat
Technique:  In situ hybridisation and immunohistochemistry
References:  36-37
Kupffer cells, neutrophils and macrophages
Species:  Rat
Technique:  RT-PCR
References:  38
Neural stem progenitor cells
Species:  Rat
Technique:  RT-PCR
References:  39
Retina (subset of ganglion cells in inner nuclear layer)
Species:  Rat
Technique:  Immunohistochemistry
References:  40
Retina (subset of ganglion cells in inner nuclear layer)
Species:  Mouse
Technique:  Immunohistochemistry
References:  41
Sperm
Species:  Mouse
Technique:  Immunohistochemistry (does not distinguish among α GlyR subtypes)
References:  42
Physiological Consequences of Altering Gene Expression
Overexpression of the D80A mutant α1 GlyR in mouse eliminates zinc potentiation of synaptic α1 GlyRs. Knock-in mice developed both motor and sensory deficits typical of impaired glycinergic transmission: inducible tremor, delayed righting reflex, abnormal gait, and an enhanced acoustic startle response.
Species:  Mouse
Tissue:  in vivo
Technique:  Homologous recombination of D80A mutant α1 GlyR at the Glra1 gene locus.
References:  20
Overexpression of the S267Q mutant α1 GlyR in mouse reulted in a decrease in alcohol sensitivity, limb clenching and an enhanced acoustic startle response. The mutation is thought to ablate the putative alcohol binding site.
Species:  Mouse
Tissue:  in vivo
Technique:  Homologous recombination of S267Q mutant α1 GlyR at the Glra1 gene locus.
References:  21-23
Clinically-Relevant Mutations
Disease:  Hereditary hyperekplexia
OMIM:  #149400
Role:  All known mutations reduce the magnitude of α1 GlyR-mediated currents, with some completely eliminating α1GlyR expression or function.
Drugs:  Clonazepam
Comments:  All mutations produce similar symptoms although the severity may vary. The main symptom in adults is an exaggerated and generalised startle reflex to unexpected and sometimes trivial stimuli. This is often accompanied by temporary but complete muscular rigidity, often resulting in unprotected falls. Neonates also usually display a severe muscular rigidity (hypertonia) that subsides throughout the first year of life.
References:  24
Click column headers to sort
Type Species Molecular location Reference
None Human Around 20 α1 GlyR mutations have been identified to date in ~70 human hyperekplexia pedigrees 24
Disease:  Spasmodic mouse
Role:  A mutation in α1 GlyR results in a 6 fold decrease in glycine sensitivity.
Comments:  Symptoms are similar to human hyperekplexia.
References:  25-26
Click column headers to sort
Type Species Molecular location Reference
None Mouse A52S 25-26
Disease:  Oscillator mouse
Role:  Homozygous oscillator mice appear normal until the second week of life, whereupon they develop progressively worsening muscular rigidity and tremor, spastic gait, exaggerated startle responses and die within 10 days.
Comments:  It is a deletion of 7 nucleotides.
References:  27-28
Click column headers to sort
Type Species Molecular location Reference
Deletion Mouse A premature stop codon in the α1 GlyR large intracellular domain. 27-28
Disease:  Cincinatti mouse
Role:  Reduction of magnitude of α1-mediated currents
Comments:  Duplication of exon 5 results in a frameshift and premature protein truncation. The symptoms are similar to human hyperekplexia.
References:  29
Click column headers to sort
Type Species Molecular location Reference
Frameshift Mouse Duplication of exon 5 29
Subunit Comments
The rat α1 subunit exists as two alternatively spliced isoforms [16], provisionally termed α1 and α1INS. The latter contains an eight amino acid insertion within the large intracellular region between TM3 and TM4 [17].

To cite this receptor data page, please use the following:

Joseph. W. Lynch.
Glycine receptors: α1. Last modified on 2010-07-01. Accessed on 2010-09-03. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=423.


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