CACNA1F

calcium voltage-gated channel subunit alpha1 F, the group of Calcium voltage-gated channel alpha1 subunits

Basic information

Region (hg38): X:49205062-49233371

Previous symbols: [ "CSNB2", "AIED" ]

Links

ENSG00000102001 ∙ NCBI:778 ∙ OMIM:300110 ∙ HGNC:1393 ∙ Uniprot:O60840 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital stationary night blindness (Supportive), mode of inheritance: AD
• cone-rod dystrophy (Supportive), mode of inheritance: AD
• Aland island eye disease (Supportive), mode of inheritance: XL
• Aland island eye disease (Definitive), mode of inheritance: XL
• congenital stationary night blindness 2A (Strong), mode of inheritance: XL
• X-linked cone-rod dystrophy 3 (Strong), mode of inheritance: XL
• Aland island eye disease (Strong), mode of inheritance: XL
• inherited retinal dystrophy (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Aland Island eye disease; Cone-rod dystrophy, X-linked, 3; Night blindness, congenital stationary, X-linked, type 2A	XL	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	14230113; 14213931; 9662400; 9662399; 11381068; 12111638; 12807962; 16505158; 17525176; 20001510; 20301423; 22194652; 22744390

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CACNA1F gene.

• not provided (1016 variants)
• Congenital stationary night blindness 2A (30 variants)
• Inborn genetic diseases (30 variants)
• not specified (23 variants)
• Retinal dystrophy (22 variants)
• Ocular albinism, type II (14 variants)
• X-linked cone-rod dystrophy 3 (13 variants)
• Congenital stationary night blindness (8 variants)
• Cone-rod dystrophy (5 variants)
• CACNA1F-related condition (4 variants)
• Retinitis pigmentosa (2 variants)
• X-linked cone-rod dystrophy 3;Ocular albinism, type II;Congenital stationary night blindness 2A (1 variants)
• Congenital stationary night blindness, type 2A, severe (1 variants)
• Abnormality of neuronal migration (1 variants)
• Myopia;Amblyopia (1 variants)
• See cases (1 variants)
• Abnormality of the eye (1 variants)
• Ocular albinism, type II;X-linked cone-rod dystrophy 3;Congenital stationary night blindness 2A (1 variants)
• Macular dystrophy (1 variants)
• Ocular albinism, type II;Congenital stationary night blindness 2A;X-linked cone-rod dystrophy 3 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CACNA1F 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			10	190	11	211
missense	2	4	455	28	13	502
nonsense	36	5				41
start loss			1			1
frameshift	27	6	2			35
inframe indel		1	10	1	1	13
splice donor/acceptor (+/-2bp)	6	28	1			35
splice region		1	26	30	4	61
non coding	1		8	101	29	139
Total	72	44	487	320	54

Highest pathogenic variant AF is 0.0000271

Variants in CACNA1F

This is a list of pathogenic ClinVar variants found in the CACNA1F region.

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

Position	Type	Phenotype	Significance	ClinVar
X-49205141-A-C			Uncertain significance (Sep 13, 2022)
X-49205145-C-T			Uncertain significance (Jan 27, 2022)
X-49205146-G-A			Likely benign (Jan 14, 2024)
X-49205151-C-T			Uncertain significance (Jul 03, 2023)
X-49205152-G-A			Likely benign (Sep 23, 2022)
X-49205164-G-A			Likely benign (Sep 04, 2021)
X-49205164-G-C			Uncertain significance (Nov 27, 2023)
X-49205175-C-T		Congenital stationary night blindness 2A	Uncertain significance (Jan 04, 2024)
X-49205184-C-G			Uncertain significance (Nov 28, 2022)
X-49205184-C-T			Uncertain significance (Jul 12, 2022)
X-49205189-C-A			Uncertain significance (Apr 20, 2022)
X-49205189-C-T			Uncertain significance (Aug 13, 2022)
X-49205190-G-A			Uncertain significance (Dec 01, 2023)
X-49205191-G-A			Likely benign (Aug 10, 2022)
X-49205192-G-A			Benign (Jun 13, 2023)
X-49205202-A-C			Uncertain significance (Feb 05, 2022)
X-49205208-C-T			Uncertain significance (May 29, 2022)
X-49205209-G-A		not specified	Benign (Jan 29, 2024)
X-49205211-C-G			Uncertain significance (Dec 11, 2023)
X-49205211-C-T			Conflicting classifications of pathogenicity (Dec 22, 2023)
X-49205212-G-A			Likely benign (Jan 18, 2023)
X-49205216-T-G			Uncertain significance (Apr 24, 2021)
X-49205228-G-A			Uncertain significance (Jan 12, 2022)
X-49205231-C-T			Uncertain significance (Dec 15, 2021)
X-49205263-C-A			Uncertain significance (Jun 25, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CACNA1F	protein_coding	protein_coding	ENST00000376265	48	28311

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000123	1.00	125712	13	22	125747	0.000139

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.60	632	845	0.748	0.0000704	12869
Missense in Polyphen		128	198.73	0.64408		3093
Synonymous	1.60	301	338	0.889	0.0000285	3980
Loss of Function	5.40	23	72.7	0.316	0.00000574	1114

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000662	0.000528
Ashkenazi Jewish	0.000140	0.0000992
East Asian	0.000435	0.000326
Finnish	0.0000644	0.0000462
European (Non-Finnish)	0.000130	0.0000879
Middle Eastern	0.000435	0.000326
South Asian	0.000272	0.000163
Other	0.000221	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Isoform 1: Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1F gives rise to L-type calcium currents. Long- lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, and by benzothiazepines. Activates at more negative voltages and does not undergo calcium-dependent inactivation (CDI), due to incoming calcium ions, during depolarization. {ECO:0000269|PubMed:27226626}.; FUNCTION: Isoform 6: Voltage-dependent L-type calcium channel activates at more hyperpolarized voltages and exibits a robust calcium-dependent inactivation (CDI), due to incoming calcium ions, during depolarizations. {ECO:0000269|PubMed:27226626}.
• Disease: DISEASE: Night blindness, congenital stationary, 2A (CSNB2A) [MIM:300071]: A non-progressive retinal disorder characterized by impaired night vision, often associated with nystagmus and myopia. {ECO:0000269|PubMed:11281458, ECO:0000269|PubMed:12111638, ECO:0000269|PubMed:12187427, ECO:0000269|PubMed:15897456, ECO:0000269|PubMed:22194652, ECO:0000269|PubMed:9662399, ECO:0000269|PubMed:9662400}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cone-rod dystrophy, X-linked 3 (CORDX3) [MIM:300476]: An inherited retinal dystrophy characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa, due to cone photoreceptors degenerating at a higher rate than rod photoreceptors. {ECO:0000269|PubMed:16505158}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Aaland island eye disease (AIED) [MIM:300600]: A retinal disease characterized by a combination of fundus hypopigmentation, decreased visual acuity due to foveal hypoplasia, nystagmus, astigmatism, protan color vision defect, myopia, and defective dark adaptation. Except for progression of axial myopia, the disease can be considered to be a stationary condition. Electroretinography reveals abnormalities in both photopic and scotopic functions. {ECO:0000269|PubMed:17525176, ECO:0000269|PubMed:22194652}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Cortisol synthesis and secretion - Homo sapiens (human);Aldosterone synthesis and secretion - Homo sapiens (human);Oxytocin signaling pathway - Homo sapiens (human);Retrograde endocannabinoid signaling - Homo sapiens (human);GABAergic synapse - Homo sapiens (human);Serotonergic synapse - Homo sapiens (human);Cardiac muscle contraction - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Dilated cardiomyopathy (DCM) - Homo sapiens (human);Arrhythmogenic right ventricular cardiomyopathy (ARVC) - Homo sapiens (human);GnRH signaling pathway - Homo sapiens (human);Alzheimer,s disease - Homo sapiens (human);Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Vascular smooth muscle contraction - Homo sapiens (human);Renin secretion - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Cholinergic synapse - Homo sapiens (human);Insulin secretion - Homo sapiens (human);Celecoxib Pathway, Pharmacodynamics;Valproic Acid Pathway, Pharmacodynamics;Pathway_PA165964473;Alzheimers Disease;Arrhythmogenic Right Ventricular Cardiomyopathy;MAPK Signaling Pathway;GPCR Dopamine D1like receptor;Phase 0 - rapid depolarisation;Phase 2 - plateau phase;Cardiac conduction;Muscle contraction (Consensus)

Recessive Scores

• pRec: 0.198

Intolerance Scores

• loftool: 0.0573
• rvis_EVS: -0.83
• rvis_percentile_EVS: 11.53

Haploinsufficiency Scores

• pHI: 0.259
• hipred: N
• hipred_score: 0.432

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.690

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cacna1f
• Phenotype: cellular 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

Zebrafish Information Network

• Gene name: cacna1fa
• Affected structure: retinal cone cell
• Phenotype tag: abnormal
• Phenotype quality: quality

Gene ontology

• Biological process: calcium ion transport;visual perception;regulation of ion transmembrane transport;T cell homeostasis;regulation of T cell receptor signaling pathway;detection of light stimulus involved in visual perception;calcium ion import;calcium ion transmembrane transport
• Cellular component: photoreceptor outer segment;plasma membrane;voltage-gated calcium channel complex;integral component of membrane;perikaryon
• Molecular function: voltage-gated calcium channel activity;high voltage-gated calcium channel activity;metal ion binding