GABRD (gamma-aminobutyric acid type A receptor subunit delta)

Gene

• Entrez ID: 2563
• Gene name: Gamma-aminobutyric acid type A receptor subunit delta
• Gene symbol: GABRD
• Synonyms (NCBI Gene): EIG10, EJM7, GABAARdelta, GEFSP5
• Chromosome: 1
• Chromosome location: 1p36.33
• Summary: Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA-A receptors, which are ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as benzodiaz

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs41307846	G>A	Benign, likely-benign, risk-factor	Coding sequence variant, missense variant
rs121434580	A>C	Risk-factor	Missense variant, coding sequence variant
rs147463074	C>T	Conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs368961588	C>T	Conflicting-interpretations-of-pathogenicity	Intron variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004888	Function	Transmembrane signaling receptor activity	IEA
GO:0004890	Function	GABA-A receptor activity	IBA
GO:0004890	Function	GABA-A receptor activity	IEA
GO:0004890	Function	GABA-A receptor activity	TAS	2176788
GO:0005216	Function	Monoatomic ion channel activity	IEA
GO:0005230	Function	Extracellular ligand-gated monoatomic ion channel activity	IEA
GO:0005254	Function	Chloride channel activity	IBA
GO:0005254	Function	Chloride channel activity	IEA
GO:0005515	Function	Protein binding	IPI	16189514, 25416956, 32296183
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	ISS
GO:0005886	Component	Plasma membrane	TAS	2176788
GO:0006811	Process	Monoatomic ion transport	IEA
GO:0006821	Process	Chloride transport	IEA
GO:0007165	Process	Signal transduction	TAS	2176788
GO:0007214	Process	Gamma-aminobutyric acid signaling pathway	IDA	35355020
GO:0007214	Process	Gamma-aminobutyric acid signaling pathway	ISS
GO:0007214	Process	Gamma-aminobutyric acid signaling pathway	NAS	28528665
GO:0007267	Process	Cell-cell signaling	IEA
GO:0007268	Process	Chemical synaptic transmission	IEA
GO:0016020	Component	Membrane	IEA
GO:0030424	Component	Axon	IEA
GO:0030425	Component	Dendrite	IEA
GO:0034220	Process	Monoatomic ion transmembrane transport	IEA
GO:0034707	Component	Chloride channel complex	IEA
GO:0043025	Component	Neuronal cell body	IEA
GO:0045211	Component	Postsynaptic membrane	IEA
GO:0051932	Process	Synaptic transmission, GABAergic	IBA
GO:0051932	Process	Synaptic transmission, GABAergic	NAS	28528665, 35355020
GO:0060078	Process	Regulation of postsynaptic membrane potential	IEA
GO:0098978	Component	Glutamatergic synapse	IEA
GO:0098982	Component	GABA-ergic synapse	IEA
GO:1902476	Process	Chloride transmembrane transport	IBA
GO:1902476	Process	Chloride transmembrane transport	IDA	35355020
GO:1902476	Process	Chloride transmembrane transport	NAS	28528665
GO:1902711	Component	GABA-A receptor complex	IBA
GO:1902711	Component	GABA-A receptor complex	IEA
GO:1902711	Component	GABA-A receptor complex	IPI	35355020
GO:1902711	Component	GABA-A receptor complex	ISS
GO:1904315	Function	Transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential	IEA

Other IDs

• MIM: 137163
• HGNC: 4084
• e!Ensembl: ENSG00000187730

Protein

• UniProt ID: O14764
• Protein name: Gamma-aminobutyric acid receptor subunit delta (GABA(A) receptor subunit delta) (GABAAR subunit delta)
• Protein function: Delta subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain (PubMed:35355020). GABA-gated chloride channels, also named GABA(A) receptors (GABAAR),
• PDB: 7QN5, 7QN6, 7QN7, 7QN8, 7QN9, 7QNC, 7QND
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF02931	Neur_chan_LBD	43 → 247	Neurotransmitter-gated ion-channel ligand binding domain	Family
  PF02932	Neur_chan_memb	254 → 408	Neurotransmitter-gated ion-channel transmembrane region	Family

• Sequence:

  MDAPARLLAPLLLLCAQQLRGTRAMNDIGDYVGSNLEISWLPNLDGLIAGYARNFRPGIG
  GPPVNVALALEVASIDHISEANMEYTMTVFLHQSWRDSRLSYNHTNETLGLDSRFVDKLW
  LPDTFIVNAKSAWFHDVTVENKLIRLQPDGVILYSIRITSTVACDMDLAKYPMDEQECML
  DLESYGYSSEDIVYYWSESQEHIHGLDKLQLAQFTITSYRFTTELMNFKSAGQFPRLSLH
  FHLRRNRGVYIIQSYMPSVLLVAMSWVSFWISQAAVPARVSLGITTVLTMTTLMVSARSS
  LPRASAIKALDVYFWICYVFVFAALVEYAFAHFNADYRKKQKAKVKVSRPRAEMDVRNAI
  VLFSLSAAGVTQELAISRRQRRVPGNLMGSYRSVGVETGETKKEGAARSGGQGGIRARLR
  PIDADTIDIYARAVFPAAFAAVNVIYWAAYAM

• Sequence length: 452

Pathways

KEGG:

Neuroactive ligand-receptor interaction
Retrograde endocannabinoid signaling
GABAergic synapse
Morphine addiction
Nicotine addiction

Associated diseases

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Epilepsy, idiopathic generalized, susceptibility to, 10	Pathogenic; Likely pathogenic	rs1659014112, rs2525640747	RCV002470247 RCV005870078
GABRD-Related Disorders	Likely pathogenic	rs2525640747	RCV006269801
Idiopathic generalized epilepsy	Likely pathogenic	rs2525644185	RCV002979282

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Adrenocortical carcinoma, hereditary	Benign	rs28398772	RCV005901338
Autism spectrum disorder	Likely benign	rs2525628997	RCV003127338
Cervical cancer	Benign	rs28398772	RCV005901339
Cholangiocarcinoma	Benign	rs28398772	RCV005901342
Colon adenocarcinoma	Benign	rs28398772	RCV005901337
EEG abnormality	Conflicting classifications of pathogenicity	rs148908731	RCV000678793
Epileptic encephalopathy	Uncertain significance	rs1057519556	RCV000417018
Familial pancreatic carcinoma	Uncertain significance	rs763656458	RCV005932115
GABRD-related disorder	Likely benign; Uncertain significance; Conflicting classifications of pathogenicity; Benign	rs375374936, rs747305505, rs376701444, rs777148022, rs148908731, rs41307846, rs576082385, rs1659017768, rs77892827, rs79386457, rs139300921, rs143115257, rs79685811, rs77557135, rs759009305, rs374718450, rs377536787, rs937477150, rs76809996, rs369490217, rs773818258	RCV003930943 RCV003963328 RCV004756435 RCV003404162 RCV003955290 RCV003974836 RCV003977116 RCV003941682 RCV003925609 RCV003960277 RCV004755995 RCV004756016 RCV003925852 RCV003972956 RCV003957990 RCV003930746 RCV003978033 RCV003903128 RCV003978137 RCV003953585 RCV004756208
Generalized epilepsy with febrile seizures plus type 5	risk factor; Benign; Likely benign	rs121434580, rs41307846	RCV000017598 RCV000017599
Intellectual disability	Likely benign	rs79386457	RCV001251987
Lung cancer	Benign; Likely benign	rs28398772, rs76809996	RCV005901343 RCV005903232
Ovarian serous cystadenocarcinoma	Benign	rs28398772	RCV005901341
Sarcoma	Benign	rs28398772	RCV005901340
See cases	Conflicting classifications of pathogenicity	rs200019257	RCV002252214
Thymoma	Likely benign	rs76809996	RCV005903231
Uterine corpus endometrial carcinoma	Likely benign	rs76809996	RCV005903233

Associations from Text Mining
Disease Name	Relationship Type	References
Adrenocortical Carcinoma	Associate	33187258
Autistic Disorder	Associate	25124326
Bipolar Disorder	Associate	31279243
Breast Neoplasms	Associate	34194536
Cleft Palate	Associate	34382870
Colonic Neoplasms	Stimulate	37181811
Colorectal Neoplasms	Associate	32396280
Colorectal Neoplasms	Stimulate	34194536
Developmental Disabilities	Associate	34633442
Epilepsy	Associate	31056551, 34633442, 38458029
Epilepsy Absence	Associate	34633442
Epilepsy Complex Partial	Associate	16452673
Epilepsy Generalized	Associate	16452673, 34633442
Epilepsy Idiopathic Generalized	Associate	16452673
Epileptic Encephalopathy Early Infantile 3	Associate	38458029
Glioma	Associate	31545245, 33969375
Intellectual Disability	Associate	34633442
Lymphoma Non Hodgkin	Associate	31545245
Mood Disorders	Associate	20561060
Myoclonic Epilepsy Juvenile	Associate	16452673
Neoplasms	Associate	26555223, 31545245, 37181811, 37543674
Nervous System Diseases	Associate	25124326
Seizures	Stimulate	33969375
Seizures Febrile	Associate	16452673