CACNG2

calcium voltage-gated channel auxiliary subunit gamma 2, the group of Calcium channel auxiliary gamma subunits

Basic information

Region (hg38): 22:36560856-36703752

Links

ENSG00000166862 ∙ NCBI:10369 ∙ OMIM:602911 ∙ HGNC:1406 ∙ Uniprot:Q9Y698 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal dominant 10 (Limited), mode of inheritance: AD
• autosomal dominant non-syndromic intellectual disability (Supportive), mode of inheritance: AD
• intellectual disability, autosomal dominant 10 (Limited), mode of inheritance: Unknown
• complex neurodevelopmental disorder (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal dominant 10	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	21376300

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CACNG2 gene.

• Inborn genetic diseases (10 variants)
• not provided (9 variants)
• Intellectual disability, autosomal dominant 10 (5 variants)
• not specified (4 variants)
• Seizure (1 variants)
• Neurodevelopmental disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CACNG2 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	7		8
missense			17			17
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region				1		1
non coding				1		1
Total	0	0	19	8	0

Variants in CACNG2

This is a list of pathogenic ClinVar variants found in the CACNG2 region.

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

Position	Type	Phenotype	Significance	ClinVar
22-36564367-C-G		Intellectual disability, autosomal dominant 10	Uncertain significance (Mar 09, 2023)
22-36564379-G-C		Intellectual disability, autosomal dominant 10	Uncertain significance (Aug 01, 2021)
22-36564458-T-C		not specified	Uncertain significance (Apr 18, 2023)
22-36564464-T-A		Seizure	Uncertain significance (Aug 18, 2019)
22-36564508-G-A		not specified	Uncertain significance (Mar 04, 2020)
22-36564564-G-T			Likely benign (Jul 13, 2018)
22-36564640-C-G		not specified	Uncertain significance (Mar 31, 2023)
22-36564654-G-C		Intellectual disability, autosomal dominant 10	Uncertain significance (Sep 17, 2021)
22-36564663-G-A		not specified	Likely benign (Sep 28, 2020)
22-36564665-C-T		not specified	Uncertain significance (Dec 01, 2022)
22-36564683-C-T		not specified • CACNG2-related disorder	Conflicting classifications of pathogenicity (Feb 18, 2019)
22-36564694-G-A		not specified	Uncertain significance (May 11, 2022)
22-36564734-C-T		Intellectual disability, autosomal dominant 10	Uncertain significance (Dec 09, 2022)
22-36564744-G-A		CACNG2-related disorder	Likely benign (Jul 01, 2023)
22-36564747-C-A		not specified	Uncertain significance (Mar 21, 2022)
22-36564774-C-A			Likely benign (Apr 01, 2022)
22-36564782-A-G		Ependymoma	Uncertain significance (Dec 29, 2017)
22-36564823-C-T		not specified	Uncertain significance (Oct 30, 2023)
22-36564840-G-A			Likely benign (Apr 01, 2023)
22-36564875-T-C		not specified	Uncertain significance (Dec 02, 2022)
22-36564893-G-T		not specified	Likely benign (Feb 09, 2015)
22-36566352-C-T		Neurodevelopmental disorder	Uncertain significance (May 16, 2022)
22-36566362-C-G		Intellectual disability, autosomal dominant 10	Pathogenic (Mar 11, 2011)
22-36566413-C-T		not specified	Uncertain significance (Apr 05, 2023)
22-36566437-C-A		not specified	Uncertain significance (Dec 08, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CACNG2	protein_coding	protein_coding	ENST00000300105	4	139636

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.923	0.0768	125735	0	1	125736	0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.09	119	203	0.587	0.0000144	2125
Missense in Polyphen		52	97.444	0.53364		968
Synonymous	-0.0718	87	86.2	1.01	0.00000685	655
Loss of Function	3.03	1	12.6	0.0793	7.81e-7	129

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000615	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
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: Regulates the trafficking and gating properties of AMPA- selective glutamate receptors (AMPARs). Promotes their targeting to the cell membrane and synapses and modulates their gating properties by slowing their rates of activation, deactivation and desensitization. Does not show subunit-specific AMPA receptor regulation and regulates all AMPAR subunits. Thought to stabilize the calcium channel in an inactivated (closed) state. {ECO:0000269|PubMed:20805473}.
• Disease: DISEASE: Mental retardation, autosomal dominant 10 (MRD10) [MIM:614256]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. {ECO:0000269|PubMed:21376300}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Oxytocin signaling pathway - Homo sapiens (human);Cardiac muscle contraction - Homo sapiens (human);Dilated cardiomyopathy (DCM) - Homo sapiens (human);Arrhythmogenic right ventricular cardiomyopathy (ARVC) - Homo sapiens (human);Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Arrhythmogenic Right Ventricular Cardiomyopathy;MAPK Signaling Pathway;Developmental Biology;GPCR Dopamine D1like receptor;Neuronal System;Phase 0 - rapid depolarisation;Phase 2 - plateau phase;Cardiac conduction;Muscle contraction;Presynaptic depolarization and calcium channel opening;Trafficking of AMPA receptors;Glutamate binding, activation of AMPA receptors and synaptic plasticity;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses;LGI-ADAM interactions (Consensus)

Recessive Scores

• pRec: 0.172

Intolerance Scores

• rvis_EVS: -0.16
• rvis_percentile_EVS: 41.25

Haploinsufficiency Scores

• pHI: 0.630
• hipred: Y
• hipred_score: 0.783
• ghis: 0.677

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.539

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cacng2
• Phenotype: 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); hearing/vestibular/ear phenotype; growth/size/body region phenotype; cellular phenotype

Zebrafish Information Network

• Gene name: cacng2b
• Affected structure: Mauthner neuron
• Phenotype tag: abnormal
• Phenotype quality: increased rate

Gene ontology

• Biological process: protein targeting to membrane;neuromuscular junction development;transmission of nerve impulse;response to calcium ion;membrane depolarization;positive regulation of synaptic transmission, glutamatergic;membrane hyperpolarization;eye blink reflex;calcium ion transmembrane transport;neurotransmitter receptor transport, postsynaptic endosome to lysosome;postsynaptic neurotransmitter receptor diffusion trapping;neurotransmitter receptor internalization;positive regulation of protein localization to basolateral plasma membrane;regulation of AMPA receptor activity;positive regulation of AMPA receptor activity
• Cellular component: cytosol;plasma membrane;voltage-gated calcium channel complex;cell surface;cell junction;endocytic vesicle membrane;AMPA glutamate receptor complex;somatodendritic compartment;cerebellar mossy fiber;Schaffer collateral - CA1 synapse;hippocampal mossy fiber to CA3 synapse;postsynaptic density membrane;glutamatergic synapse;integral component of postsynaptic density membrane
• Molecular function: voltage-gated calcium channel activity;calcium channel activity;protein binding;channel regulator activity;ionotropic glutamate receptor binding