GNAT2

G protein subunit alpha transducin 2, the group of G protein subunits alpha, group i

Basic information

Region (hg38): 1:109603090-109619929

Links

ENSG00000134183 ∙ NCBI:2780 ∙ OMIM:139340 ∙ HGNC:4394 ∙ Uniprot:P19087 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• achromatopsia 4 (Strong), mode of inheritance: AR
• achromatopsia 4 (Moderate), mode of inheritance: AR
• achromatopsia 4 (Strong), mode of inheritance: AR
• cone dystrophy (Supportive), mode of inheritance: AD
• achromatopsia (Supportive), mode of inheritance: AR
• achromatopsia 4 (Definitive), mode of inheritance: AR
• GNAT2-related retinopathy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Achromatopsia 4	AR	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	Ophthalmologic	12205108; 12077706; 15557429; 21107338

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GNAT2 gene.

• not provided (177 variants)
• Achromatopsia 4 (41 variants)
• Inborn genetic diseases (8 variants)
• not specified (6 variants)
• Achromatopsia (2 variants)
• Retinal dystrophy (2 variants)
• Cone dystrophy (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GNAT2 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			1	31	1	33
missense	2		80	3	1	86
nonsense	4					4
start loss						0
frameshift	5	1				6
inframe indel			2			2
splice donor/acceptor (+/-2bp)	2	4				6
splice region		1	9	8		18
non coding			6	17	2	25
Total	13	5	89	51	4

Highest pathogenic variant AF is 0.0000329

Variants in GNAT2

This is a list of pathogenic ClinVar variants found in the GNAT2 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-109603252-G-T		Achromatopsia 4	Uncertain significance (Jan 13, 2018)
1-109603304-C-G		Achromatopsia 4	Uncertain significance (Apr 27, 2017)
1-109603361-A-G			Uncertain significance (Mar 19, 2022)
1-109603362-G-A		Inborn genetic diseases • Achromatopsia 4	Uncertain significance (Jan 22, 2024)
1-109603366-G-A			Likely benign (Jan 06, 2022)
1-109603384-T-G			Uncertain significance (Feb 22, 2020)
1-109603388-A-G		Inborn genetic diseases • Achromatopsia 4	Uncertain significance (Apr 11, 2023)
1-109603394-A-G			Uncertain significance (Feb 11, 2022)
1-109603421-T-A			Uncertain significance (Jun 01, 2019)
1-109603449-T-C			Uncertain significance (Mar 20, 2022)
1-109603452-T-C		Inborn genetic diseases	Uncertain significance (Dec 04, 2023)
1-109603453-G-C			Uncertain significance (Nov 28, 2023)
1-109603463-AT-A		Achromatopsia 4	Pathogenic (Jun 12, 2018)
1-109603470-T-C			Uncertain significance (Jan 16, 2021)
1-109603476-C-T		Achromatopsia 4	Uncertain significance (Jun 12, 2018)
1-109603481-C-T			Uncertain significance (Sep 13, 2022)
1-109603482-G-A		Achromatopsia 4	Pathogenic (Nov 08, 2023)
1-109603486-A-G		not specified • Achromatopsia 4	Conflicting classifications of pathogenicity (Jan 24, 2024)
1-109603487-T-C			Uncertain significance (Jan 19, 2021)
1-109603488-T-C			Uncertain significance (Dec 14, 2023)
1-109603491-G-A		Achromatopsia 4	Conflicting classifications of pathogenicity (Dec 06, 2023)
1-109603497-G-C			Uncertain significance (Jul 30, 2022)
1-109603510-T-C			Uncertain significance (Aug 23, 2022)
1-109603513-G-T		Abnormality of the eye	Likely pathogenic (Jan 01, 2015)
1-109603519-C-G			Likely benign (Nov 08, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GNAT2	protein_coding	protein_coding	ENST00000351050	8	9791

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000695	0.910	125718	0	30	125748	0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.663	161	186	0.863	0.0000102	2372
Missense in Polyphen		71	82.227	0.86347		1099
Synonymous	0.0217	71	71.2	0.997	0.00000418	636
Loss of Function	1.62	11	18.6	0.593	0.00000118	215

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000304	0.000304
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000163	0.000163
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000106	0.000105
Middle Eastern	0.000163	0.000163
South Asian	0.000196	0.000196
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. Transducin is an amplifier and one of the transducers of a visual impulse that performs the coupling between rhodopsin and cGMP-phosphodiesterase.
• Pathway: Phototransduction - Homo sapiens (human);Signaling by GPCR;Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding;Signaling by WNT;Signal Transduction;Metabolism of proteins;Chaperonin-mediated protein folding;Ca2+ pathway;Beta-catenin independent WNT signaling;Protein folding;G-protein activation;PLC beta mediated events;G-protein mediated events;Opioid Signalling;G alpha (i) signalling events;GPCR downstream signalling;Visual signal transduction: Cones (Consensus)

Recessive Scores

• pRec: 0.168

Intolerance Scores

• loftool: 0.303
• rvis_EVS: 0.02
• rvis_percentile_EVS: 55.22

Haploinsufficiency Scores

• pHI: 0.442
• hipred: Y
• hipred_score: 0.567
• ghis: 0.413

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0545

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gnat2
• Phenotype: 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); vision/eye phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: gnat2
• Affected structure: melanocyte
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: detection of chemical stimulus involved in sensory perception of bitter taste;protein folding;G protein-coupled receptor signaling pathway;adenylate cyclase-modulating G protein-coupled receptor signaling pathway;positive regulation of cytosolic calcium ion concentration;Wnt signaling pathway, calcium modulating pathway;visual perception;phototransduction;response to light intensity;retinal cone cell development;detection of light stimulus involved in visual perception
• Cellular component: photoreceptor outer segment;photoreceptor inner segment;heterotrimeric G-protein complex;plasma membrane;photoreceptor outer segment membrane
• Molecular function: G protein-coupled receptor binding;GTPase activity;GTP binding;G protein-coupled photoreceptor activity;G-protein beta/gamma-subunit complex binding;metal ion binding