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GLRA1 Gene

protein-coding GIFtS: 67
GCID: GC05M151182

Glycine Receptor, Alpha 1

(Previous names: glycine receptor, alpha 1 (startle disease/hyperekplexia))
(Previous symbol: STHE)

See GLRA1-related diseases
at

MalaCards

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, ¹⁰fRNAdb, ¹²H-InvDB, ¹³NCBI, ¹⁴NONCODE, and/or ¹⁵RNAdb)
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Aliases
Glycine Receptor, Alpha 1¹ ²		Glycine Receptor, Alpha 1 (Startle Disease/Hyperekplexia)¹
STHE¹ ² ⁵		Startle Disease/Hyperekplexia¹
Glycine Receptor 48 KDa Subunit² ³		Stiff Person Syndrome¹
Glycine Receptor Strychnine-Binding Subunit² ³		Glycine Receptor Subunit Alpha-1²
HKPX1² ⁵

External Ids:	HGNC: 4326¹	Entrez Gene: 2741²	Ensembl: ENSG00000145888⁷	OMIM: 138491⁵	UniProtKB: P23415³

Export aliases for GLRA1 gene to outside databases

Previous GC identifers: GC05M151270 GC05M151799 GC05M151230 GC05M146347

(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for GLRA1 Gene:

The protein encoded by this gene is a subunit of a pentameric inhibitory glycine receptor. The receptor mediates

postsynaptic inhibition in the central nervous system. Defects in this gene are a cause of startle disease

(STHE), also known as hereditary hyperekplexia or congenital stiff-person syndrome. Two transcript variants

encoding different isoforms have been found for this gene.(provided by RefSeq, Mar 2009)

GeneCards Summary for GLRA1 Gene:

GLRA1 (glycine receptor, alpha 1) is a protein-coding gene. Diseases associated with GLRA1 include sporadic hyperekplexia, and stiff-person syndrome. GO annotations related to this gene include transmitter-gated ion channel activity and glycine binding. An important paralog of this gene is GLRA2.

UniProtKB/Swiss-Prot: GLRA1_HUMAN, P23415

Function: The glycine receptor is a neurotransmitter-gated ion channel. Binding of glycine to its receptor

increases the chloride conductance and thus produces hyperpolarization (inhibition of neuronal firing)

summary for GLRA1 Gene:

Glycine receptors (GlyR) are members of the cys-loop family of ligand-gated ion channels, responsible for

mediating the inhibitory effects of glycine. They are widely distributed throughout the CNS, particularly

within the hippocampus, spinal cord and brain stem. Glycine receptors exist as pentameric proteins,

homo-oligomers of the alpha isoforms (alpha1, alpha2, alpha3 or alpha4) or hetero-oligomers which also

contain the beta-subtype variant (beta1) which is essential for targeting the receptor to the synapse.

Glycine receptors contain an integral chloride channel, and have modulatory sites for anesthetics,

neurosteroids, cannabinoids and ethanol. Disruption in glycine receptor expression or ion channel function

can result in hyperekplexia, a rare neurological disorder.

Gene Wiki entry for GLRA1 (Glycine receptor, alpha 1) Gene

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:

NC_000005.9 NT_029289.12 NC_018916.2

Regulatory elements:

Regulatory transcription factor binding sites in the GLRA1 gene promoter:
NF-1 AP-4 Tal-1beta E47 RORalpha1 COMP1 Sox9 FOXO1a ITF-2
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: GLRA1 promoter sequence

Search Chromatin IP Primers for GLRA1

Epigenetics:

DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat GLRA1

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 5q32 Ensembl cytogenetic band: 5q33.1 HGNC cytogenetic band: 5q33.1

GLRA1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
GLRA1 gene location

GeneLoc information about chromosome 5 GeneLoc Exon Structure

GeneLoc location for GC05M151182: view genomic region (about GC identifiers)

Start:	151,202,074 bp from pter	End:	151,304,403 bp from pter
Size:	102,330 bases	Orientation:	minus strand

(According to ¹UniProtKB, HORDE, ²neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: GLRA1_HUMAN, P23415 (See protein sequence)

Recommended Name: Glycine receptor subunit alpha-1 precursor

Size: 457 amino acids; 52624 Da

Subunit: Pentamer composed of three alpha and two beta subunits. Homopentamers of alpha subunits also form

functional receptors

Miscellaneous: The alpha subunit binds strychnine

4 PDB 3D structures from and Proteopedia for GLRA1:

1MOT (3D)

1VRY (3D)

2M6B (3D)

2M6I (3D)

Secondary accessions: B2R6T3 Q14C77 Q6DJV9

Alternative splicing: 2 isoforms: P23415-1 P23415-2

Explore the universe of human proteins at neXtProt for GLRA1: NX_P23415

Explore proteomics data for GLRA1 at MOPED

Post-translational modifications:

Glycosylation² at Asn66

Modification sites at PhosphoSitePlus

See GLRA1 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

REFSEQ proteins (2 alternative transcripts):

NP_000162.2 NP_001139512.1

ENSEMBL proteins:

ENSP00000274576 ENSP00000430595 ENSP00000411593 ENSP00000445913

Reactome Protein details: P23415

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(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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HGNC Gene Families:

GLRA: Ligand-gated ion channels / Glycine receptors

IUPHAR Guide to PHARMACOLOGY protein family classification: alpha1

Glycine receptors

Selected InterPro protein domains (see all 7):

IPR008128 Glycine_rcpt_A1

IPR008127 Glycine_rcpt_A

IPR018000 Neurotransmitter_ion_chnl_CS

IPR006028 GABAA_rcpt

IPR006201 Neur_channel

Graphical View of Domain Structure for InterPro Entry P23415

ProtoNet protein and cluster: P23415

3 Blocks protein domains:

IPB006028 Gamma-aminobutyric acid A (GABAA) receptor signature

IPB006201 Neurotransmitter-gated ion-channel

IPB008128 Glycine receptor alpha 1 subunit signature

UniProtKB/Swiss-Prot: GLRA1_HUMAN, P23415

Similarity: Belongs to the ligand-gated ion channel (TC 1.A.9) family. Glycine receptor (TC 1.A.9.3) subfamily.

GLRA1 sub-subfamily

Find genes that share domains with GLRA1 About GenesLikeMe

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, genOway,
transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Molecular Function:

UniProtKB/Swiss-Prot Summary: GLRA1_HUMAN, P23415

Function: The glycine receptor is a neurotransmitter-gated ion channel. Binding of glycine to its receptor

increases the chloride conductance and thus produces hyperpolarization (inhibition of neuronal firing)

Genatlas biochemistry entry for GLRA1:

glycine receptor,alpha 1 subunit,inhibitory

Gene Ontology (GO): Selected molecular function terms (see all 6): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005230	extracellular ligand-gated ion channel activity	--	--
GO:0005515	protein binding	IPI	11929858
GO:0016594	glycine binding	IDA	15748848
GO:0016934	extracellular-glycine-gated chloride channel activity	IMP	7920629
GO:0022824	transmitter-gated ion channel activity	IEA	--

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Phenotypes:
12 MGI mutant phenotypes (inferred from 9 alleles) (MGI details for Glra1):

adipose tissue	behavior/neurological	growth/size/body	hematopoietic system	immune system
mortality/aging	muscle	nervous system	no phenotypic analysis	reproductive system
respiratory system	vision/eye

Find genes that share phenotypes with GLRA1 About GenesLikeMe

Animal Models:

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In Situ Assay
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(According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Subcellular locations from UniProtKB/Swiss-Prot

GLRA1_HUMAN, P23415: Cell junction, synapse, postsynaptic cell membrane; Multi-pass membrane protein. Cell

membrane; Multi-pass membrane protein

Subcellular locations from COMPARTMENTS:

Compartment	Confidence
plasma membrane	5
endoplasmic reticulum	2
peroxisome	1

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Gene Ontology (GO): Selected cellular component terms (see all 12): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005622	intracellular	--	--
GO:0005783	endoplasmic reticulum	--	--
GO:0005886	plasma membrane	TAS	--
GO:0005887	integral component of plasma membrane	NAS	2155780
GO:0009897	external side of plasma membrane	IEA	--

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(SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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SuperPaths for GLRA1 About

See pathways by source

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SuperPath

Contained pathways About

Ion channel transport

Ion channel transport

0.58

Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds

Transmembrane transport of small molecules

0.47

Ca-dependent events

Neurophysiological process PGE2-induced pain processing

0.38

Peptide ligand-binding receptors

Neuroactive ligand-receptor interaction

0.36

Ligand-gated ion channel transport

Ligand-gated ion channel transport

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Pathways by source See SuperPaths
Show all pathways

1 GeneGo (Thomson Reuters) Pathway for GLRA1

Neurophysiological process PGE2-induced pain processing

1 Reactome Pathway for GLRA1

Ligand-gated ion channel transport

1 Kegg Pathway (Kegg details for GLRA1):

Neuroactive ligand-receptor interaction

Custom Pathway & Disease-focused RT² Profiler PCR Arrays for GLRA1
Interactions:

Search GeneGlobe Interaction Network for GLRA1

STRING Interaction Network Preview (showing 5 interactants - click image to see 6)

Selected Interacting proteins for GLRA1 (ENSP00000274576⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 6)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
GLRA2	ENSP00000218075⁴	STRING: ENSP00000218075
GLRA3	ENSP00000274093⁴	STRING: ENSP00000274093
GLRB	ENSP00000264428⁴	STRING: ENSP00000264428
GPHN	ENSP00000303019⁴	STRING: ENSP00000303019
KIF5A	ENSP00000286452⁴	STRING: ENSP00000286452

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Gene Ontology (GO): Selected biological process terms (see all 26): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0001508	action potential	IEA	--
GO:0001964	startle response	IMP	11973623
GO:0002087	regulation of respiratory gaseous exchange by neurological system process	IEA	--
GO:0006810	transport	--	--
GO:0006811	ion transport	IDA	2155780

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(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse compounds at ApexBio

Compounds for GLRA1 available from Tocris Bioscience About this table

Compound	Action	CAS #
beta-Alanine	Endogenous glycine agonist, more selective than taurine (Cat. No. 0209)	[107-95-9]
Hypotaurine	Non-selective endogenous glycine receptor agonist	[300-84-5]
L-Serine	Weak endogenous glycine receptor agonist	[56-45-1]
L-Alanine	Glycine receptor agonist	[56-41-7]
Taurine	Non-selective, endogenous glycine receptor partial agonist	[107-35-7]

4 HMDB Compounds for GLRA1 About this table

Compound	Synonyms	CAS #	PubMed Ids
Chlorine	Cl2 (see all 13)	16887-00-6	--
Ethanol	1-Hydroxyethane (see all 57)	64-17-5	--
Glycine	2-Aminoacetate (see all 15)	56-40-6	--
Taurine	1-Aminoethane-2-sulfonate (see all 14)	107-35-7	--

Selected DrugBank Compounds for GLRA1 (see all 11) About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
Ethanol	Absolute Alcohol (see all 34)	64-17-5	target	agonist	20713066 17139284 9452448 17016423 21044637
Desflurane	Desflurano [INN-Spanish] (see all 2)	57041-67-5	target	agonist	17139284 17016423 16973644
Enflurane	Anesthetic 347 (see all 7)	13838-16-9	target	agonist	17139284 17016423 16973644
Halothane	2-Bromo-2-Chloro-1,1,1-Trifluoroethane (see all 14)	151-67-7	target	allosteric modulator	15287733 17139284 17016423
Isoflurane	--	26675-46-7	target	agonist	17139284 17016423 16973644
Methoxyflurane	Methoflurane (see all 11)	76-38-0	target	agonist	10683198 17139284 17016423
Glycine	2-Aminoacetic acid (see all 4)	56-40-6	target	--	17154252 16884688
Lindane	Benzene hexachloride (see all 11)	58-89-9	target	antagonist	20600211 12614680
Sevoflurane	Sevofluran (see all 3)	28523-86-6	target	agonist	17139284 17016423
D-Serine	--	312-84-5	target	--	11752352

Selected IUPHAR Ligands for GLRA1 (alpha1) (see all 21) About this table

Ligand	Type	Action	Affinity	Pubmed IDs
Zn²⁺	Allosteric regulator	Potentiation	7.4	--
anandamide	Allosteric regulator	Potentiation	7.4	--
HU-210	Allosteric regulator	Potentiation	6.6	--
ginkgolide B	Channel blocker	None	5.1 - 6.2	--
ginkgolide X	Antagonist	Antagonist	6.1	--
cyanotriphenylborate	Channel blocker	None	5.9	--
pregnenolone sulphate	Antagonist	Antagonist	5.7	--
nifedipine	Antagonist	Antagonist	5.5	--
Delta⁹-tetrahydrocannabinol	Allosteric regulator	Potentiation	5.5	--
Cu²⁺	Allosteric regulator	Inhibition	4.8 - 5.4	--

5 Novoseek inferred chemical compound relationships for GLRA1 gene About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
clonazepam	71.6	2	1355335 (1), 16429380 (1)
strychnine	68.2	1	9144769 (1)
picrotoxin	36.8	1	11744711 (1)
glutamate	7.99	1	20525074 (1)
arginine	7.81	1	11973623 (1)

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(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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REFSEQ mRNAs for GLRA1 gene (2 alternative transcripts):

NM_000171.3 NM_001146040.1

Unigene Cluster for GLRA1:

Glycine receptor, alpha 1

Hs.121490 [show with all ESTs]

Unigene Representative Sequence: NM_001146040

5 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000274576(uc003lur.3 uc003lut.3 uc003lus.3) ENST00000462581

ENST00000455880 ENST00000471351 ENST00000545569

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Additional mRNA sequence:

AK308539.1 AK312702.1 BC074980.2 BC114947.1 X52009.1

2 DOTS entries:

DT.92014914 DT.120823005

3 AceView cDNA sequences:

BC074980 X52009 NM_000171

GeneLoc Exon Structure

2 Alternative Splicing Database (ASD) splice patterns (SP) for GLRA1 About this scheme

ExUns:	1	^	2	^	3	^	4a	·	4b	^	5	^	6	^	7	^	8	^	9
SP1:
SP2:			-

ECgene alternative splicing isoforms for GLRA1

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE ¹MOPED, ²PaxDb, and ³MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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GLRA1 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS <intensity>^2/3
CGAP TAG: --

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GLRA1 expression in embryonic tissues and stem cells About this table

Data from LifeMap, the Embryonic Development and Stem Cells Database
selected tissues (see all 4) fully expand


Skeletal Muscle (Muscoskeletal System) fully expand to see all 2 entries
Myoblasts Mandibular Arch Muscles

NULL (Uncategorized)
Neural rosettes

Neurons
Type1 Off Cone Bipolar Cells Inner Nuclear Layer

Eye (Sensory Organs)
Type1 Off Cone Bipolar Cells Inner Nuclear Layer

GLRA1 Protein expression data from MOPED¹, PaxDb² and MaxQB³:

About this image

GLRA1 Protein Expression

SOURCE GeneReport for Unigene cluster: Hs.121490

Custom PCR Arrays for GLRA1

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In Situ
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(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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This gene was present in the common ancestor of animals.

Orthologs for GLRA1 gene from Selected species (see all 16) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	Glra1^{1 , 5}	glycine receptor, alpha 1 subunit^{1, 5}	90.72(n)¹ 98.66(a)¹		11 (33.12 cM)⁵ 14654¹ NM_020492.3¹ NP_065238.2¹ 55514238⁵
chicken (Gallus gallus)	Aves	GLRA1¹	glycine receptor, alpha 1	84.11(n) 96.21(a)		427637 XM_425210.3 XP_425210.3
lizard (Anolis carolinensis)	Reptilia	GLRA1⁶	glycine receptor, alpha 1	86(a)	1 ↔ 1	GL343248.1(114481-208717)
tropical clawed frog (Xenopus tropicalis)	Amphibia	glra1¹	glycine receptor, alpha 1	78.92(n) 89.06(a)		100498379 XM_004912727.1 XP_004912784.1
zebrafish (Danio rerio)	Actinopterygii	glra1²	glycine receptor, alpha 1	79.54(n)		30676 AF488379.1
fruit fly (Drosophila melanogaster)	Insecta	Rdl³ GluClalpha¹	response to cyclodiene GABA-A receptor³ GluClalpha¹	44(a) (best of 6)³ 50.64(n)¹ 41.72(a)¹		3 67A1³ 42350¹ NM_001275811.1¹ NP_001262740.1¹
worm (Caenorhabditis elegans)	Secernentea	glc-3^{1 , 3}	ligand-gated ionic channel subunit³ glc-3¹	47(a) (best of 21)³ 51.86(n)¹ 50.17(a)¹		V(5449241-5453240)³ 178930¹ NM_072040.5¹ NP_504441.1¹

ENSEMBL Gene Tree for GLRA1 (if available)
TreeFam Gene Tree for GLRA1 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
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Paralogs for GLRA1 gene

GLRA2² GABRR1² GLRB² GABRB1² GABRR3² GABRD² GABRP² GLRA4²

GABRB3² GABRB2² GABRQ² GLRA3² GABRR2²

Selected SIMAP similar genes for GLRA1 using alignment to 3 protein entries: GLRA1_HUMAN (see all proteins) (see all similar genes):

GLRA2 GLRA3 GLRA4 GABRP GABRA4 GABRQ

GABRR3 GABRR2 GABRA2 GABRR1 GABRA5 GABRE

GABRA1 GABRD GABRG3 GLRB GABRG2 GABRA6

Find genes that share paralogs with GLRA1 About GenesLikeMe

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, ⁴UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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SNP ID	Valid	Clinical significance	Chr 5 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
VAR_000296⁴		Hyperekplexia 1 (HKPX1)⁴	--	see VAR_000296	2	I N	mis⁴		0	--	--	--	--
VAR_000299⁴		Hyperekplexia 1 (HKPX1)⁴	--	see VAR_000299	2	R Q	mis⁴		0	--	--	--	--
VAR_010114⁴		Hyperekplexia 1 (HKPX1)⁴	--	see VAR_010114	2	R H	mis⁴		0	--	--	--	--
VAR_000300⁴		Hyperekplexia 1 (HKPX1)⁴	--	see VAR_000300	2	K E	mis⁴		0	--	--	--	--
VAR_000298⁴		Hyperekplexia 1 (HKPX1)⁴	--	see VAR_000298	2	R L	mis⁴		0	--	--	--	--
VAR_000301⁴		Hyperekplexia 1 (HKPX1)⁴	--	see VAR_000301	2	Y C	mis⁴		0	--	--	--	--
VAR_010112⁴		Hyperekplexia 1 (HKPX1)⁴	--	see VAR_010112	2	P T	mis⁴		0	--	--	--	--
VAR_000297⁴		Hyperekplexia 1 (HKPX1)⁴	--	see VAR_000297	2	Q H	mis⁴		0	--	--	--	--
VAR_010113⁴		Hyperekplexia 1 (HKPX1)⁴	--	see VAR_010113	2	R H	mis⁴		0	--	--	--	--
rs116474260^1,2	C,F	pathogenic¹	151475976(+)	`TGGGCC/TCATCC`	4	S G	mis¹		3		NA EU	5991

HapMap Linkage Disequilibrium report for GLRA1 (151202074 - 151304403 bp)

Structural Variations
Database of Genomic Variants (DGV) 3 variations for GLRA1: About this table

Variant ID	Type	Subtype	PubMed ID
esv2677174	CNV	Deletion	23128226
esv272818	CNV	Insertion	20981092
esv28315	CNV	Loss	19812545

Human Gene Mutation Database (HGMD): GLRA1
Locus Specific Mutation Databases (LSDB): GLRA1

Site Specific Mutation Identification with PCR Assays

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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OMIM gene information: 138491
OMIM disorders: 149400
UniProtKB/Swiss-Prot: GLRA1_HUMAN, P23415

Hyperekplexia 1 (HKPX1) [MIM:149400]: A neurologic disorder characterized by muscular rigidity of central

nervous system origin, particularly in the neonatal period, and by an exaggerated startle response to unexpected

acoustic or tactile stimuli. Note=The disease is caused by mutations affecting the gene represented in this entry

7 diseases for GLRA1:
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sporadic hyperekplexia stiff-person syndrome hyperekplexia glra1-related hyperekplexia

hyperekplexia, hereditary 1, autosomal dominant or recessive aspiration pneumonia molybdenum cofactor deficiency

1 inferred disease relationship from the University of Copenhagen DISEASES database for GLRA1:

Aspiration pneumonia

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2 Novoseek inferred disease relationships for GLRA1 gene About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
hyperekplexia	98.6	67	8651283 (3), 10514101 (3), 7611730 (3), 14580232 (3) (see all 37)
neurological disorders	61.9	5	7620586 (1), 12359314 (1), 11781706 (1), 7925268 (1) (see all 5)

GeneTests: GLRA1
GeneReviews: GLRA1
Genetic Association Database (GAD): GLRA1
Human Genome Epidemiology (HuGE) Navigator: GLRA1 (5 documents)

Export disorders for GLRA1 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
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PubMed articles for GLRA1 gene, integrated from 10 sources (see all 164):
(articles sorted by number of sources associating them with GLRA1)

Utopia: connect your pdf to the dynamic
world of online information

Mutations in the alpha 1 subunit of the inhibitory glycine receptor cause the dominant neurologic disorder, hyperekplexia. (PubMed id 8298642)^{1, 2, 3, 9} Shiang R....Wasmuth J.J. (Nat. Genet. 1993)
Mutational analysis of familial and sporadic hyperekplexia. (PubMed id 7611730)^{1, 2, 9} Shiang R.... Wasmuth J.J. (Ann. Neurol. 1995)
Hyperekplexia phenotype due to compound heterozygosity for GLRA1 gene mutations. (PubMed id 10514101)^{1, 2, 9} Vergouwe M.N.... Frants R.R. (Ann. Neurol. 1999)
Novel GLRA1 missense mutation (P250T) in dominant hyperekplexia defines an intracellular determinant of glycine receptor channel gating. (PubMed id 9920650)^{1, 2, 9} Saul B....Becker C.-M. (J. Neurosci. 1999)
Analysis of GLRA1 in hereditary and sporadic hyperekplexia: a novel mutation in a family cosegregating for hyperekplexia and spastic paraparesis. (PubMed id 8733061)^{1, 2, 9} Elmslie F.V.... Rees M. (J. Med. Genet. 1996)
Alanine-scanning mutagenesis in the signature disulfide loop of the glycine receptor alpha 1 subunit: critical residues for activation and modulation. (PubMed id 15287733)^{1, 7, 9} Schofield C.M....Harrison N.L. (Biochemistry 2004)
A novel mutation (Gln266-->His) in the alpha 1 subunit of the inhibitory glycine-receptor gene (GLRA1) in hereditary hyperekplexia. (PubMed id 8571969)^{1, 2, 9} Milani N.... Larizza L. (Am. J. Hum. Genet. 1996)
Startle disease, or hyperekplexia: response to clonazepam and assignment of the gene (STHE) to chromosome 5q by linkage analysis. (PubMed id 1355335)^{1, 3, 9} Ryan S.G....Mackey R.W. (Ann. Neurol. 1992)
Decreased agonist affinity and chloride conductance of mutant glycine receptors associated with human hereditary hyperekplexia. (PubMed id 7925268)^{1, 2, 9} Langosch D....Betz H. (EMBO J. 1994)
Identification of new putative susceptibility genes for several psychiatric disorders by association analysis of regulatory and non-synonymous SNPs of 306 genes involved in neurotransmission and neurodevelopment. (PubMed id 19086053)^{1, 4} GratacA^s M....Carracedo A. (Am. J. Med. Genet. B Neuropsychiatr. Genet. 2009)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 2741	HGNC: 4326	AceView: GLRA1	Ensembl:ENSG00000145888	euGenes: HUgn2741
ECgene: GLRA1	Kegg: 2741	H-InvDB: GLRA1

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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Name	Description
PharmGKB entry for GLRA1	Pharmacogenomics, SNPs, Pathways
GeneReviews	http://www.ncbi.nlm.nih.gov/books/NBK1116/?term=GLRA1[genesymbol]

Intellectual Property for GLRA1 gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

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Patent Information for GLRA1 gene:
Search GeneIP for patents involving GLRA1

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

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GLRA1 Gene

Glycine Receptor, Alpha 1

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GLRA1 Gene

Glycine Receptor, Alpha 1

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