CACNA2D3

calcium voltage-gated channel auxiliary subunit alpha2delta 3, the group of Calcium voltage-gated channel auxiliary alpha2delta subunits

Basic information

Region (hg38): 3:54122546-55074557

Links

ENSG00000157445 ∙ NCBI:55799 ∙ OMIM:606399 ∙ HGNC:15460 ∙ Uniprot:Q8IZS8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CACNA2D3 gene.

• Inborn genetic diseases (53 variants)
• not provided (13 variants)
• CACNA2D3-related condition (6 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CACNA2D3 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	2	3
missense			46	1	1	48
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding			10	3	5	18
Total	0	0	57	5	8

Variants in CACNA2D3

This is a list of pathogenic ClinVar variants found in the CACNA2D3 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-54122720-G-C		not specified	Uncertain significance (Dec 08, 2023)
3-54122727-G-T		not specified	Uncertain significance (Oct 25, 2023)
3-54122729-TCGCCG-T			not provided (-)
3-54122748-G-A		not specified	Uncertain significance (Dec 08, 2023)
3-54122753-G-A		not specified	Uncertain significance (Aug 26, 2022)
3-54122790-C-T		not specified	Uncertain significance (Nov 08, 2022)
3-54123535-T-C		not specified	Uncertain significance (Aug 15, 2023)
3-54123552-A-C		not specified	Uncertain significance (Oct 04, 2023)
3-54123560-C-T		not specified	Uncertain significance (Dec 20, 2021)
3-54123563-C-T		not specified	Uncertain significance (Nov 10, 2022)
3-54123582-G-C		not specified	Uncertain significance (Aug 02, 2021)
3-54123583-C-G		not specified	Uncertain significance (Sep 20, 2023)
3-54320459-G-GA		CACNA2D3-related disorder	Uncertain significance (Jul 27, 2023)
3-54320483-T-T			Benign (Dec 17, 2018)
3-54320553-G-A		not specified	Uncertain significance (Feb 06, 2023)
3-54386694-G-GTTTTT		CACNA2D3-related disorder	Likely benign (Jan 21, 2020)
3-54386721-G-A		not specified	Uncertain significance (May 27, 2022)
3-54562834-A-C		not specified	Uncertain significance (Jan 23, 2023)
3-54562853-G-A		not specified	Uncertain significance (Oct 26, 2022)
3-54562904-G-A		not specified	Uncertain significance (Nov 10, 2022)
3-54562940-A-C			Benign (Apr 30, 2021)
3-54569796-G-T		CACNA2D3-related disorder	Likely benign (May 27, 2022)
3-54569847-C-A		not specified	Uncertain significance (Jun 10, 2022)
3-54581822-A-C		not specified	Uncertain significance (Aug 01, 2022)
3-54581847-T-G		CACNA2D3-related disorder	Benign (Jan 13, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CACNA2D3	protein_coding	protein_coding	ENST00000474759	38	952011

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.578	0.422	124649	0	23	124672	0.0000922

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.86	451	577	0.782	0.0000314	7200
Missense in Polyphen		181	255.5	0.7084		3024
Synonymous	-0.0763	218	217	1.01	0.0000132	1964
Loss of Function	5.99	15	68.5	0.219	0.00000367	812

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000117	0.000117
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000557	0.0000556
Finnish	0.000195	0.000186
European (Non-Finnish)	0.000107	0.000106
Middle Eastern	0.0000557	0.0000556
South Asian	0.0000659	0.0000654
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Acts as a regulatory subunit for P/Q-type calcium channel (CACNA1A), N-type (CACNA1B), L-type (CACNA1C OR CACNA1D) but not T-type (CACNA1G) (By similarity). {ECO:0000250}.
• 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);Celecoxib Pathway, Pharmacodynamics;Arrhythmogenic Right Ventricular Cardiomyopathy;MAPK Signaling Pathway;Neuronal System;Phase 0 - rapid depolarisation;Phase 2 - plateau phase;Cardiac conduction;Muscle contraction;Presynaptic depolarization and calcium channel opening;Transmission across Chemical Synapses (Consensus)

Intolerance Scores

• rvis_EVS: -0.84
• rvis_percentile_EVS: 11.45

Haploinsufficiency Scores

• pHI: 0.661
• hipred: Y
• hipred_score: 0.614
• ghis: 0.546

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.178

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cacna2d3
• Phenotype: 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); homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Gene ontology

• Biological process: regulation of ion transmembrane transport;calcium ion transmembrane transport
• Cellular component: plasma membrane;voltage-gated calcium channel complex
• Molecular function: voltage-gated calcium channel activity;metal ion binding