GABRD

gamma-aminobutyric acid type A receptor subunit delta, the group of Gamma-aminobutyric acid type A receptor subunits

Basic information

Region (hg38): 1:2019328-2030758

Links

ENSG00000187730 ∙ NCBI:2563 ∙ OMIM:137163 ∙ HGNC:4084 ∙ Uniprot:O14764 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• epilepsy, idiopathic generalized, susceptibility to, 10 (Limited), mode of inheritance: AD
• epilepsy, idiopathic generalized, susceptibility to, 10 (Limited), mode of inheritance: AD
• complex neurodevelopmental disorder (Moderate), mode of inheritance: AD
• epilepsy (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GABRD gene.

• Idiopathic generalized epilepsy (292 variants)
• not provided (42 variants)
• Epilepsy, idiopathic generalized, susceptibility to, 10 (23 variants)
• Inborn genetic diseases (12 variants)
• not specified (9 variants)
• Epileptic encephalopathy (1 variants)
• GABRD-related condition (1 variants)
• Epilepsy, juvenile myoclonic 7 (1 variants)
• See cases (1 variants)
• Autism spectrum disorder (1 variants)
• Intellectual disability (1 variants)
• Generalized epilepsy with febrile seizures plus type 5 (1 variants)
• EEG abnormality (1 variants)
• Seizure (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GABRD gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			6	98	11	115
missense	1	1	127	9		138
nonsense			2			2
start loss						0
frameshift			4			4
inframe indel			3			3
splice donor/acceptor (+/-2bp)						0
splice region			7	16	1	24
non coding			6	32	8	46
Total	1	1	148	139	19

Variants in GABRD

This is a list of pathogenic ClinVar variants found in the GABRD region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-2019420-G-A			Uncertain significance (Oct 07, 2019)
1-2019430-G-T		Idiopathic generalized epilepsy • Inborn genetic diseases	Uncertain significance (Nov 19, 2023)
1-2019437-C-G		Idiopathic generalized epilepsy	Uncertain significance (Nov 29, 2022)
1-2019437-C-T		Idiopathic generalized epilepsy	Uncertain significance (May 30, 2022)
1-2019438-C-T		Idiopathic generalized epilepsy	Likely benign (Nov 07, 2023)
1-2019439-C-G		Idiopathic generalized epilepsy	Uncertain significance (Aug 22, 2022)
1-2019444-G-T		Idiopathic generalized epilepsy	Likely benign (Dec 07, 2023)
1-2019453-G-A		Idiopathic generalized epilepsy	Likely benign (Sep 03, 2023)
1-2019472-C-A		Idiopathic generalized epilepsy	Uncertain significance (Jan 15, 2023)
1-2019477-G-T		Inborn genetic diseases	Uncertain significance (Oct 17, 2023)
1-2019479-T-G		Idiopathic generalized epilepsy	Uncertain significance (Oct 09, 2023)
1-2019482-G-A		Idiopathic generalized epilepsy	Uncertain significance (Mar 12, 2022)
1-2019483-C-G		Idiopathic generalized epilepsy	Likely benign (Nov 22, 2023)
1-2019483-C-T		Idiopathic generalized epilepsy	Likely benign (Feb 16, 2023)
1-2019484-G-A		Idiopathic generalized epilepsy	Uncertain significance (Jul 20, 2019)
1-2019487-A-G		Idiopathic generalized epilepsy	Uncertain significance (Jun 22, 2023)
1-2019488-C-T		Idiopathic generalized epilepsy	Uncertain significance (Apr 04, 2019)
1-2019489-C-G		Idiopathic generalized epilepsy	Likely benign (Nov 27, 2023)
1-2019490-A-G		Idiopathic generalized epilepsy	Uncertain significance (Feb 04, 2023)
1-2019496-G-C		Idiopathic generalized epilepsy	Uncertain significance (Sep 01, 2022)
1-2019498-G-T		Idiopathic generalized epilepsy	Likely benign (Aug 31, 2022)
1-2019501-C-T		Idiopathic generalized epilepsy	Likely benign (Nov 24, 2023)
1-2019508-C-G		Idiopathic generalized epilepsy	Likely benign (Dec 19, 2023)
1-2019509-G-A		Idiopathic generalized epilepsy	Benign (Jan 15, 2024)
1-2019511-G-A		Idiopathic generalized epilepsy	Likely benign (Jul 09, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GABRD	protein_coding	protein_coding	ENST00000378585	9	11413

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.993	0.00655	125155	0	6	125161	0.0000240

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.17	189	293	0.644	0.0000208	2901
Missense in Polyphen		94	163.27	0.57573		1613
Synonymous	-2.23	172	139	1.24	0.0000115	928
Loss of Function	3.87	1	19.4	0.0516	9.16e-7	215

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000918	0.0000910
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000276	0.0000266
Middle Eastern	0.00	0.00
South Asian	0.0000378	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
• Disease: DISEASE: Generalized epilepsy with febrile seizures plus 5 (GEFS+5) [MIM:613060]: A rare autosomal dominant, familial condition with incomplete penetrance and large intrafamilial variability. Patients display febrile seizures persisting sometimes beyond the age of 6 years and/or a variety of afebrile seizure types. This disease combines febrile seizures, generalized seizures often precipitated by fever at age 6 years or more, and partial seizures, with a variable degree of severity. {ECO:0000269|PubMed:15115768}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Epilepsy, idiopathic generalized 10 (EIG10) [MIM:613060]: A disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Juvenile myoclonic epilepsy 7 (EJM7) [MIM:613060]: A subtype of idiopathic generalized epilepsy. Patients have afebrile seizures only, with onset in adolescence (rather than in childhood) and myoclonic jerks which usually occur after awakening and are triggered by sleep deprivation and fatigue. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: Retrograde endocannabinoid signaling - Homo sapiens (human);GABAergic synapse - Homo sapiens (human);Nicotine addiction - Homo sapiens (human);Neuroactive ligand-receptor interaction - Homo sapiens (human);Morphine addiction - Homo sapiens (human);Prader-Willi and Angelman Syndrome;GABA receptor Signaling (Consensus)

Recessive Scores

• pRec: 0.170

Intolerance Scores

• loftool: 0.0118
• rvis_EVS: -0.51
• rvis_percentile_EVS: 21.65

Haploinsufficiency Scores

• pHI: 0.148
• hipred: Y
• hipred_score: 0.837
• ghis: 0.546

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.896

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Gabrd
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: signal transduction;chemical synaptic transmission;ion transmembrane transport;regulation of membrane potential;nervous system process;regulation of postsynaptic membrane potential;chloride transmembrane transport
• Cellular component: integral component of plasma membrane;cell junction;chloride channel complex;neuron projection;synapse;glutamatergic synapse;GABA-ergic synapse;integral component of postsynaptic membrane;GABA-A receptor complex
• Molecular function: GABA-A receptor activity;extracellular ligand-gated ion channel activity;chloride channel activity;protein binding;transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential