CAMK2D
calcium/calmodulin dependent protein kinase II delta, the group of Calmodulin dependent protein kinases
Basic information
Region (hg38): 4:113418054-113761927
Previous symbols: [ "CAMKD" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- See cases (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CAMK2D 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 | |||||
| missense | 8 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 1 | 1 | ||||
| non coding | 1 | |||||
| Total | 1 | 0 | 6 | 0 | 3 |
Variants in CAMK2D
This is a list of pathogenic ClinVar variants found in the CAMK2D region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 4-113457433-C-G | not specified | Uncertain significance (Apr 09, 2024) | ||
| 4-113465556-A-G | not specified | Uncertain significance (Aug 08, 2023) | ||
| 4-113509643-C-T | not specified | Uncertain significance (Aug 16, 2021) | ||
| 4-113513360-A-G | not specified | Uncertain significance (Jun 27, 2019) | ||
| 4-113513852-A-G | Neurodevelopmental disorder | Pathogenic (Mar 07, 2022) | ||
| 4-113513860-C-G | Neurodevelopmental disorder | Pathogenic (Mar 07, 2022) | ||
| 4-113513909-C-T | Neurodevelopmental disorder | Pathogenic (Mar 07, 2022) | ||
| 4-113513912-T-G | Neurodevelopmental disorder | Pathogenic (Mar 07, 2022) | ||
| 4-113515139-T-C | not specified | Uncertain significance (Dec 17, 2021) | ||
| 4-113515168-C-T | Benign (May 30, 2018) | |||
| 4-113515201-T-C | Benign (May 29, 2018) | |||
| 4-113517631-C-T | See cases | Pathogenic (Feb 08, 2023) | ||
| 4-113517662-A-G | Benign (Dec 31, 2019) | |||
| 4-113537357-G-T | Benign (Jul 19, 2018) | |||
| 4-113537442-G-A | Neurodevelopmental disorder | Pathogenic (Mar 07, 2022) | ||
| 4-113609151-C-A | Neurodevelopmental disorder | Pathogenic (Mar 07, 2022) | ||
| 4-113609162-C-T | not specified | Uncertain significance (Dec 15, 2023) | ||
| 4-113609191-C-T | Neurodevelopmental disorder | Pathogenic (Mar 07, 2022) | ||
| 4-113661737-G-A | not specified | Uncertain significance (May 27, 2022) | ||
| 4-113759386-T-C | not specified | Uncertain significance (Apr 26, 2024) | ||
| 4-113761032-C-T | not specified | Uncertain significance (May 30, 2024) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| CAMK2D | protein_coding | protein_coding | ENST00000342666 | 18 | 310896 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.00229 | 0.998 | 125730 | 0 | 15 | 125745 | 0.0000596 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.11 | 124 | 267 | 0.465 | 0.0000133 | 3286 |
| Missense in Polyphen | 56 | 160.78 | 0.34829 | 2031 | ||
| Synonymous | 1.65 | 68 | 87.7 | 0.775 | 0.00000422 | 904 |
| Loss of Function | 3.63 | 11 | 33.8 | 0.325 | 0.00000170 | 416 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000582 | 0.0000582 |
| Ashkenazi Jewish | 0.0000994 | 0.0000992 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.0000465 | 0.0000462 |
| European (Non-Finnish) | 0.0000619 | 0.0000615 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.0000655 | 0.0000653 |
| Other | 0.000164 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Calcium/calmodulin-dependent protein kinase involved in the regulation of Ca(2+) homeostatis and excitation-contraction coupling (ECC) in heart by targeting ion channels, transporters and accessory proteins involved in Ca(2+) influx into the myocyte, Ca(2+) release from the sarcoplasmic reticulum (SR), SR Ca(2+) uptake and Na(+) and K(+) channel transport. Targets also transcription factors and signaling molecules to regulate heart function. In its activated form, is involved in the pathogenesis of dilated cardiomyopathy and heart failure. Contributes to cardiac decompensation and heart failure by regulating SR Ca(2+) release via direct phosphorylation of RYR2 Ca(2+) channel on 'Ser- 2808'. In the nucleus, phosphorylates the MEF2 repressor HDAC4, promoting its nuclear export and binding to 14-3-3 protein, and expression of MEF2 and genes involved in the hypertrophic program. Is essential for left ventricular remodeling responses to myocardial infarction. In pathological myocardial remodeling acts downstream of the beta adrenergic receptor signaling cascade to regulate key proteins involved in ECC. Regulates Ca(2+) influx to myocytes by binding and phosphorylating the L-type Ca(2+) channel subunit beta-2 CACNB2. In addition to Ca(2+) channels, can target and regulate the cardiac sarcolemmal Na(+) channel Nav1.5/SCN5A and the K+ channel Kv4.3/KCND3, which contribute to arrhythmogenesis in heart failure. Phosphorylates phospholamban (PLN/PLB), an endogenous inhibitor of SERCA2A/ATP2A2, contributing to the enhancement of SR Ca(2+) uptake that may be important in frequency-dependent acceleration of relaxation (FDAR) and maintenance of contractile function during acidosis. May participate in the modulation of skeletal muscle function in response to exercise, by regulating SR Ca(2+) transport through phosphorylation of PLN/PLB and triadin, a ryanodine receptor- coupling factor. {ECO:0000269|PubMed:16690701, ECO:0000269|PubMed:17179159}.;
- Pathway
- Inflammatory mediator regulation of TRP channels - Homo sapiens (human);Aldosterone synthesis and secretion - Homo sapiens (human);Oxytocin signaling pathway - Homo sapiens (human);Long-term potentiation - Homo sapiens (human);Neurotrophin signaling pathway - Homo sapiens (human);Dopaminergic synapse - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Oocyte meiosis - Homo sapiens (human);HIF-1 signaling pathway - Homo sapiens (human);GnRH signaling pathway - Homo sapiens (human);ErbB signaling pathway - Homo sapiens (human);Gastric acid secretion - Homo sapiens (human);Circadian entrainment - Homo sapiens (human);Axon guidance - Homo sapiens (human);Glucagon signaling pathway - Homo sapiens (human);Glioma - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);Necroptosis - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Tuberculosis - Homo sapiens (human);Amphetamine addiction - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Wnt signaling pathway - Homo sapiens (human);Cholinergic synapse - Homo sapiens (human);Olfactory transduction - Homo sapiens (human);Insulin secretion - Homo sapiens (human);Melanogenesis - Homo sapiens (human);EGFR Inhibitor Pathway, Pharmacodynamics;Physiological and Pathological Hypertrophy of the Heart;MicroRNAs in cardiomyocyte hypertrophy;SRF and miRs in Smooth Muscle Differentiation and Proliferation;Cardiac Hypertrophic Response;Myometrial Relaxation and Contraction Pathways;NO-cGMP-PKG mediated Neuroprotection;Wnt Signaling Pathway;Calcium Regulation in the Cardiac Cell;Signal Transduction;HSF1-dependent transactivation;bioactive peptide induced signaling pathway;regulation of pgc-1a;transcription factor creb and its extracellular signals;stathmin and breast cancer resistance to antimicrotubule agents;Ion channel transport;Cytokine Signaling in Immune system;Cellular responses to stress;Immune System;Ion homeostasis;Transport of small molecules;Neuronal System;Phase 0 - rapid depolarisation;Cardiac conduction;Muscle contraction;Cellular responses to external stimuli;IL-7 signaling;Ion transport by P-type ATPases;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;JAK STAT pathway and regulation;Cellular response to heat stress;EPO signaling;Trafficking of AMPA receptors;Interferon gamma signaling;IFN-gamma pathway;Glutamate binding, activation of AMPA receptors and synaptic plasticity;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses;Ras activation upon Ca2+ influx through NMDA receptor;CREB phosphorylation through the activation of Ras;Unblocking of NMDA receptor, glutamate binding and activation;CREB phosphorylation through the activation of CaMKII;Post NMDA receptor activation events;Activation of NMDA receptor and postsynaptic events;VEGF;ca-calmodulin-dependent protein kinase activation;Notch-mediated HES/HEY network;Interferon Signaling
(Consensus)
Recessive Scores
- pRec
- 0.240
Intolerance Scores
- loftool
- 0.921
- rvis_EVS
- 0.02
- rvis_percentile_EVS
- 55.22
Haploinsufficiency Scores
- pHI
- 0.116
- hipred
- Y
- hipred_score
- 0.756
- ghis
- 0.578
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.991
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Camk2d
- 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); 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); cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype;
Gene ontology
- Biological process
- MAPK cascade;regulation of cell growth;regulation of the force of heart contraction;regulation of membrane depolarization;regulation of transcription by RNA polymerase II;protein phosphorylation;regulation of heart contraction;positive regulation of cardiac muscle hypertrophy;regulation of cell communication by electrical coupling;positive regulation of cardiac muscle cell apoptotic process;regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum;regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion;peptidyl-serine phosphorylation;peptidyl-threonine phosphorylation;endoplasmic reticulum calcium ion homeostasis;protein autophosphorylation;protein complex oligomerization;relaxation of cardiac muscle;regulation of ryanodine-sensitive calcium-release channel activity;interferon-gamma-mediated signaling pathway;regulation of cellular localization;cellular response to calcium ion;cardiac muscle cell contraction;regulation of heart rate by cardiac conduction;regulation of cardiac muscle cell action potential;regulation of cardiac muscle cell action potential involved in regulation of contraction;regulation of histone deacetylase activity;regulation of cell communication by electrical coupling involved in cardiac conduction;regulation of relaxation of cardiac muscle;negative regulation of sodium ion transmembrane transport;regulation of calcium ion transmembrane transport via high voltage-gated calcium channel;negative regulation of sodium ion transmembrane transporter activity
- Cellular component
- nucleus;nucleoplasm;cytoplasm;cytosol;plasma membrane;membrane;endocytic vesicle membrane;sarcoplasmic reticulum membrane;sarcolemma;neuron projection
- Molecular function
- protein serine/threonine kinase activity;calmodulin-dependent protein kinase activity;Ras guanyl-nucleotide exchange factor activity;protein binding;calmodulin binding;ATP binding;sodium channel inhibitor activity;titin binding;identical protein binding;protein homodimerization activity;ion channel binding