GNAL

G protein subunit alpha L, the group of G protein subunits alpha, group s

Basic information

Region (hg38): 18:11689263-11885685

Links

ENSG00000141404 ∙ NCBI:2774 ∙ OMIM:139312 ∙ HGNC:4388 ∙ Uniprot:P38405 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• dystonia 25 (Strong), mode of inheritance: AD
• dystonia 25 (Strong), mode of inheritance: AD
• dystonia 25 (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Dystonia 25	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	23222958

ClinVar

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

• not provided (107 variants)
• Dystonic disorder (90 variants)
• Inborn genetic diseases (23 variants)
• Dystonia 25 (9 variants)
• not specified (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GNAL 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			4	19	8	31
missense	2	2	38	1	1	44
nonsense	2	1				3
start loss	1					1
frameshift	2	1				3
inframe indel			2	1	3	6
splice donor/acceptor (+/-2bp)		1				1
splice region			6	8	2	16
non coding			18	34	54	106
Total	7	5	62	55	66

Variants in GNAL

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

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

Position	Type	Phenotype	Significance	ClinVar
18-11689453-C-T			Benign (Jul 05, 2018)
18-11689523-T-C		Dystonia 25	Benign (Aug 10, 2021)
18-11689572-G-C		Dystonic disorder	Likely benign (Jul 27, 2023)
18-11689600-G-T			Uncertain significance (Jun 01, 2019)
18-11689609-G-C		Dystonic disorder	Uncertain significance (Aug 26, 2021)
18-11689611-G-A		Dystonic disorder	Likely benign (Dec 20, 2018)
18-11689626-G-T			Uncertain significance (Jul 01, 2017)
18-11689632-G-A		Dystonic disorder	Uncertain significance (Sep 06, 2017)
18-11689634-A-G			Uncertain significance (Jul 01, 2022)
18-11689670-C-T			Likely benign (Jul 17, 2018)
18-11689670-CGGCCCT-C		GNAL-related disorder	Benign (May 07, 2019)
18-11689670-C-CGGCCCT		Dystonic disorder	Benign (Jan 22, 2024)
18-11689700-G-A		Dystonic disorder	Benign (Jan 22, 2024)
18-11689714-A-C		Inborn genetic diseases	Uncertain significance (Sep 16, 2021)
18-11689756-C-T		not specified	Uncertain significance (Oct 06, 2023)
18-11689757-G-A		Dystonic disorder	Uncertain significance (Jul 24, 2018)
18-11689809-T-TGCCGAGGAGCGCGAGGCG			Uncertain significance (Feb 01, 2024)
18-11689812-C-G		not specified	Uncertain significance (Nov 22, 2023)
18-11689813-G-GAGGAGCGCGAGGCGGCCA			Likely benign (Jan 01, 2023)
18-11689815-G-A		Dystonic disorder • GNAL-related disorder	Benign/Likely benign (Jan 30, 2024)
18-11689824-G-A		Dystonic disorder • GNAL-related disorder	Benign (Jan 07, 2020)
18-11689828-G-A			Uncertain significance (Feb 01, 2017)
18-11689831-A-G		Dystonic disorder	Uncertain significance (Aug 29, 2018)
18-11689834-G-A		Dystonic disorder	Uncertain significance (Dec 20, 2018)
18-11689874-G-A		Dystonia 25	Uncertain significance (May 08, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GNAL	protein_coding	protein_coding	ENST00000334049	12	196730

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.998	0.00171	125048	0	1	125049	0.00000400

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.34	87	229	0.380	0.0000127	2995
Missense in Polyphen		23	123.55	0.18616		1430
Synonymous	0.466	83	88.6	0.937	0.00000541	861
Loss of Function	4.25	1	23.0	0.0435	0.00000121	276

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. G(olf) alpha mediates signal transduction within the olfactory neuroepithelium and the basal ganglia. May be involved in some aspect of visual transduction, and in mediating the effect of one or more hormones/neurotransmitters.
• Pathway: Dopaminergic synapse - Homo sapiens (human);Amoebiasis - Homo sapiens (human);Chagas disease (American trypanosomiasis) - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);Parkinson,s disease - Homo sapiens (human);Olfactory transduction - Homo sapiens (human);G Protein Signaling Pathways;Signaling by GPCR;Signal Transduction;Olfactory Signaling Pathway;G alpha (s) signalling events;Neuronal System;Adenylate cyclase inhibitory pathway;Inhibition of adenylate cyclase pathway;Activation of GABAB receptors;GABA B receptor activation;Rapid glucocorticoid signaling;GABA receptor activation;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses;Adenylate cyclase activating pathway;G-protein mediated events;Opioid Signalling;G alpha (i) signalling events;GPCR downstream signalling;LPA4-mediated signaling events;Plasma membrane estrogen receptor signaling;Endothelins (Consensus)

Recessive Scores

• pRec: 0.189

Intolerance Scores

• loftool: 0.0256
• rvis_EVS: -0.3
• rvis_percentile_EVS: 32.62

Haploinsufficiency Scores

• pHI: 0.370
• hipred: Y
• hipred_score: 0.792
• ghis: 0.572

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.743

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gnal
• Phenotype: taste/olfaction phenotype; growth/size/body region phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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)

Gene ontology

• Biological process: signal transduction;adenylate cyclase-modulating G protein-coupled receptor signaling pathway;adenylate cyclase-activating G protein-coupled receptor signaling pathway;adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway;sensory perception of smell
• Cellular component: heterotrimeric G-protein complex;plasma membrane;extracellular exosome
• Molecular function: G protein-coupled receptor binding;GTPase activity;GTP binding;G-protein beta/gamma-subunit complex binding;metal ion binding