Details for: CACNA1F

Gene ID: 778

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: CACNA1F

Ensembl ID: ENSG00000102001

Description: calcium voltage-gated channel subunit alpha1 F

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • ON-bipolar cell CL0000749
    CSI 4.37
    rCSI 6.49%
    PRS 95.75
  • OFF-bipolar cell CL0000750
    CSI 2.75
    rCSI 3.77%
    PRS 95.47
  • retinal rod cell CL0000604
    CSI 2.67
    rCSI 4.71%
    PRS 94.44
  • retinal bipolar neuron CL0000748
    CSI 2.39
    rCSI 4.48%
    PRS 92.77
  • rod bipolar cell CL0000751
    CSI 2.28
    rCSI 4.1%
    PRS 94.25
  • retinal cone cell CL0000573
    CSI 1.97
    rCSI 3.18%
    PRS 92.45
  • S cone cell CL0003050
    CSI 1.43
    rCSI 6.28%
    PRS 94.01

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [CACNA1F](/details-gene/778) encodes the alpha-1F subunit of the L-type voltage-gated calcium channel, also known as Cav1.4. This gene is integral to the function of the central nervous system, with its expression being highly specialized to the retina. Functionally, it is crucial for calcium ion influx at the synaptic terminals of photoreceptors and bipolar cells, a key step in the transmission of visual signals. Mutations in [CACNA1F](/details-gene/778) are well-established causes of several X-linked hereditary retinal disorders, most notably incomplete congenital stationary night blindness (CSNB2) ([153245](https://omim.org/entry/153245), [Link](https://doi.org/10.1038/940)), Aland Island eye disease ([300600](https://omim.org/entry/300600), [Link](https://doi.org/10.1167/iovs.06-1103)), and cone-rod dystrophy ([300476](https://omim.org/entry/300476), [Link](https://doi.org/10.1136/jmg.2006.040741)), highlighting its indispensable role in visual perception. ## Cellular Roles and Expression Landscape The expression profile of [CACNA1F](/details-gene/778) demonstrates remarkable specificity for neuronal cell types within the retina, underscoring its specialized function in the visual system. **Overall**, the gene exhibits its highest significance in cells responsible for phototransduction and downstream signal processing. It is most prominently expressed in [ON-bipolar cell](/details-cell/CL0000749) (CSI: 4.37) and [OFF-bipolar cell](/details-cell/CL0000750) (CSI: 2.75), which are critical for relaying signals from photoreceptors to ganglion cells. High significance is also observed directly in photoreceptor cells, including the [retinal rod cell](/details-cell/CL0000604) (CSI: 2.67) and [retinal cone cell](/details-cell/CL0000573) (CSI: 1.97). This distinct expression pattern establishes [CACNA1F](/details-gene/778) as a key component of the synaptic machinery at the photoreceptor-bipolar cell synapse, where it regulates neurotransmitter release in response to light stimuli. The collective high significance in [retinal bipolar neuron](/details-cell/CL0000748) and various photoreceptor subtypes confirms its central role in the primary visual signal transduction pathway. ## Pathways and Molecular Function The functional annotations for [CACNA1F](/details-gene/778) are highly consistent with its cellular expression pattern and established role in retinal physiology. As a core component of the '[Voltage-gated calcium channel complex](/details-go/GO:0005891)', its primary molecular function is '[High voltage-gated calcium channel activity](/details-go/GO:0008331)'. This activity facilitates the biological process of '[Calcium ion import across plasma membrane](/details-go/GO:0098703)', which is essential for synaptic transmission. These functions are executed within specific cellular compartments, such as the '[Photoreceptor outer segment](/details-go/GO:0001750)' and the '[Perikaryon](/details-go/GO:0043204)' of retinal neurons. Ultimately, these molecular events are integral to the high-level biological process of '[Detection of light stimulus involved in visual perception](/details-go/GO:0050908)' and overall '[Visual perception](/details-go/GO:0007601)'. The gene's involvement in '[Protein binding](/details-go/GO:0005515)' suggests it functions within a larger protein complex that modulates its activity, a notion supported by studies on splice variants and interacting proteins ([Link](https://doi.org/10.1074/jbc.m116.731737)). ## Research Directions The well-defined role of [CACNA1F](/details-gene/778) in monogenic retinal disorders provides a clear basis for further investigation into disease mechanisms and potential therapeutics. The spectrum of diseases associated with [CACNA1F](/details-gene/778) mutations, ranging from stationary night blindness to progressive cone-rod dystrophy, suggests that the functional consequences of different mutations are not uniform. This allelic heterogeneity likely translates to distinct electrophysiological defects in specific retinal cell types. Based on the available data, several testable hypotheses can be proposed: 1. The phenotypic variability observed in patients (e.g., CSNB2 vs. cone-rod dystrophy) is caused by specific mutations in [CACNA1F](/details-gene/778) that differentially alter channel kinetics (e.g., voltage-dependence of activation, inactivation rates) in [retinal rod cell](/details-cell/CL0000604) versus [retinal cone cell](/details-cell/CL0000573) pathways. 2. The expression of distinct C-terminal splice variants of [CACNA1F](/details-gene/778) ([Link](https://doi.org/10.1074/jbc.m116.731737)) in [ON-bipolar cell](/details-cell/CL0000749) versus [OFF-bipolar cell](/details-cell/CL0000750) leads to the formation of different channel complexes, enabling unique signal processing properties in the ON and OFF visual pathways. To test the first hypothesis, one could generate patient-specific induced pluripotent stem cells (iPSCs) from individuals with different [CACNA1F](/details-gene/778)-related disorders and differentiate them into retinal organoids. Patch-clamp electrophysiology could then be performed on identified photoreceptors and bipolar cells within these organoids to directly measure and compare the aberrant Cav1.4 channel properties conferred by each mutation, correlating biophysical defects with clinical phenotype. **Therapeutic Potential** Given that [CACNA1F](/details-gene/778)-linked diseases are caused by loss-of-function mutations, the primary therapeutic strategy would be **restoration** of function rather than inhibition. The high specificity of its expression to the retina makes it an excellent candidate for gene therapy. An adeno-associated virus (AAV)-based vector carrying a functional copy of the [CACNA1F](/details-gene/778) coding sequence could be delivered via subretinal injection to transduce photoreceptors and bipolar cells. This approach aims to restore normal calcium channel activity and rescue the visual signaling deficits, representing a promising avenue for treating these inherited forms of blindness.

Genular Protein ID: 3856544691

Symbol: CAC1F_HUMAN

Name: Voltage-gated calcium channel subunit alpha Cav1.4

UniProtKB Accession Codes:

O60840 A6NI29 F5CIQ9 O43901 O95226 Q9UHB1

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CTD 1 ChEBI 3 ChEMBL 1 ChiTaRS 1 DNASU 1 DisGeNET 1 DrugBank 33 DrugCentral 1 EMBL 8 Ensembl 3 ExpressionAtlas 1 GO 11 Gene3D 4 GeneCards 1 GeneReviews 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 GuidetoPHARMACOLOGY 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 8 KEGG 1 MANE-Select 1 MIM 7 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 3 OrthoDB 1 PANTHER 2 PRINTS 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 4 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 RNAct 1 RefSeq 3 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9662399

Title: An L-type calcium-channel gene mutated in incomplete X-linked congenital stationary night blindness.

PubMed ID: 9662399

DOI: 10.1038/940

PubMed ID: 9662400

Title: Loss-of-function mutations in a calcium-channel alpha1-subunit gene in Xp11.23 cause incomplete X-linked congenital stationary night blindness.

PubMed ID: 9662400

DOI: 10.1038/947

PubMed ID: 10873387

Title: Isolation and characterization of a calcium channel gene, cacna1f, the murine orthologue of the gene for incomplete X-linked congenital stationary night blindness.

PubMed ID: 10873387

DOI: 10.1006/geno.2000.6204

PubMed ID: 19029287

Title: Expression and 1,4-dihydropyridine-binding properties of brain L-type calcium channel isoforms.

PubMed ID: 19029287

DOI: 10.1124/mol.108.049981

PubMed ID: 15772651

Title: The DNA sequence of the human X chromosome.

PubMed ID: 15772651

DOI: 10.1038/nature03440

PubMed ID: 9344658

Title: Sequence-based exon prediction around the synaptophysin locus reveals a gene-rich area containing novel genes in human proximal Xp.

PubMed ID: 9344658

DOI: 10.1006/geno.1997.4941

PubMed ID: 27226626

Title: Characterization of C-terminal Splice Variants of Cav1.4 Ca2+ Channels in Human Retina.

PubMed ID: 27226626

DOI: 10.1074/jbc.m116.731737

PubMed ID: 11281458

Title: A summary of 20 CACNA1F mutations identified in 36 families with incomplete X-linked congenital stationary night blindness, and characterization of splice variants.

PubMed ID: 11281458

DOI: 10.1007/s004390100461

PubMed ID: 12111638

Title: Thirty distinct CACNA1F mutations in 33 families with incomplete type of XLCSNB and Cacna1f expression profiling in mouse retina.

PubMed ID: 12111638

DOI: 10.1038/sj.ejhg.5200828

PubMed ID: 12187427

Title: Infantile and childhood retinal blindness: a molecular perspective (The Franceschetti Lecture).

PubMed ID: 12187427

DOI: 10.1076/opge.23.2.71.2214

PubMed ID: 15897456

Title: A CACNA1F mutation identified in an X-linked retinal disorder shifts the voltage dependence of Cav1.4 channel activation.

PubMed ID: 15897456

DOI: 10.1073/pnas.0501907102

PubMed ID: 16960802

Title: Mutations in CABP4, the gene encoding the Ca2+-binding protein 4, cause autosomal recessive night blindness.

PubMed ID: 16960802

DOI: 10.1086/508067

PubMed ID: 16505158

Title: X linked cone-rod dystrophy, CORDX3, is caused by a mutation in the CACNA1F gene.

PubMed ID: 16505158

DOI: 10.1136/jmg.2006.040741

PubMed ID: 17525176

Title: A novel CACNA1F gene mutation causes Aland Island eye disease.

PubMed ID: 17525176

DOI: 10.1167/iovs.06-1103

PubMed ID: 22194652

Title: A novel p.Gly603Arg mutation in CACNA1F causes Aland island eye disease and incomplete congenital stationary night blindness phenotypes in a family.

PubMed ID: 22194652

Sequence Information:

  • Length: 1977
  • Mass: 220678
  • Checksum: 354336550C6D8E73
  • Sequence:
    • MSESEGGKDT TPEPSPANGA GPGPEWGLCP GPPAVEGESS GASGLGTPKR RNQHSKHKTV 
AVASAQRSPR ALFCLTLANP LRRSCISIVE WKPFDILILL TIFANCVALG VYIPFPEDDS 
NTANHNLEQV EYVFLVIFTV ETVLKIVAYG LVLHPSAYIR NGWNLLDFII VVVGLFSVLL 
EQGPGRPGDA PHTGGKPGGF DVKALRAFRV LRPLRLVSGV PSLHIVLNSI MKALVPLLHI 
ALLVLFVIII YAIIGLELFL GRMHKTCYFL GSDMEAEEDP SPCASSGSGR ACTLNQTECR 
GRWPGPNGGI TNFDNFFFAM LTVFQCVTME GWTDVLYWMQ DAMGYELPWV YFVSLVIFGS 
FFVLNLVLGV LSGEFSKERE KAKARGDFQK QREKQQMEED LRGYLDWITQ AEELDMEDPS 
ADDNLGSMAE EGRAGHRPQL AELTNRRRGR LRWFSHSTRS THSTSSHASL PASDTGSMTE 
TQGDEDEEEG ALASCTRCLN KIMKTRVCRR LRRANRVLRA RCRRAVKSNA CYWAVLLLVF 
LNTLTIASEH HGQPVWLTQI QEYANKVLLC LFTVEMLLKL YGLGPSAYVS SFFNRFDCFV 
VCGGILETTL VEVGAMQPLG ISVLRCVRLL RIFKVTRHWA SLSNLVASLL NSMKSIASLL 
LLLFLFIIIF SLLGMQLFGG KFNFDQTHTK RSTFDTFPQA LLTVFQILTG EDWNVVMYDG 
IMAYGGPFFP GMLVCIYFII LFICGNYILL NVFLAIAVDN LASGDAGTAK DKGGEKSNEK 
DLPQENEGLV PGVEKEEEEG ARREGADMEE EEEEEEEEEE EEEEEGAGGV ELLQEVVPKE 
KVVPIPEGSA FFCLSQTNPL RKGCHTLIHH HVFTNLILVF IILSSVSLAA EDPIRAHSFR 
NHILGYFDYA FTSIFTVEIL LKMTVFGAFL HRGSFCRSWF NMLDLLVVSV SLISFGIHSS 
AISVVKILRV LRVLRPLRAI NRAKGLKHVV QCVFVAIRTI GNIMIVTTLL QFMFACIGVQ 
LFKGKFYTCT DEAKHTPQEC KGSFLVYPDG DVSRPLVRER LWVNSDFNFD NVLSAMMALF 
TVSTFEGWPA LLYKAIDAYA EDHGPIYNYR VEISVFFIVY IIIIAFFMMN IFVGFVIITF 
RAQGEQEYQN CELDKNQRQC VEYALKAQPL RRYIPKNPHQ YRVWATVNSA AFEYLMFLLI 
LLNTVALAMQ HYEQTAPFNY AMDILNMVFT GLFTIEMVLK IIAFKPKHYF TDAWNTFDAL 
IVVGSIVDIA VTEVNNGGHL GESSEDSSRI SITFFRLFRV MRLVKLLSKG EGIRTLLWTF 
IKSFQALPYV ALLIAMIFFI YAVIGMQMFG KVALQDGTQI NRNNNFQTFP QAVLLLFRCA 
TGEAWQEIML ASLPGNRCDP ESDFGPGEEF TCGSNFAIAY FISFFMLCAF LIINLFVAVI 
MDNFDYLTRD WSILGPHHLD EFKRIWSEYD PGAKGRIKHL DVVALLRRIQ PPLGFGKLCP 
HRVACKRLVA MNMPLNSDGT VTFNATLFAL VRTSLKIKTE GNLEQANQEL RIVIKKIWKR 
MKQKLLDEVI PPPDEEEVTV GKFYATFLIQ DYFRKFRRRK EKGLLGNDAA PSTSSALQAG 
LRSLQDLGPE MRQALTCDTE EEEEEGQEGV EEEDEKDLET NKATMVSQPS ARRGSGISVS 
LPVGDRLPDS LSFGPSDDDR GTPTSSQPSV PQAGSNTHRR GSGALIFTIP EEGNSQPKGT 
KGQNKQDEDE EVPDRLSYLD EQAGTPPCSV LLPPHRAQRY MDGHLVPRRR LLPPTPAGRK 
PSFTIQCLQR QGSCEDLPIP GTYHRGRNSG PNRAQGSWAT PPQRGRLLYA PLLLVEEGAA 
GEGYLGRSSG PLRTFTCLHV PGTHSDPSHG KRGSADSLVE AVLISEGLGL FARDPRFVAL 
AKQEIADACR LTLDEMDNAA SDLLAQGTSS LYSDEESILS RFDEEDLGDE MACVHAL