ISL1
ISL LIM homeobox 1, the group of LIM class homeoboxes
Basic information
Region (hg38): 5:51383447-51394730
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the ISL1 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 | 14 | ||||
| missense | 19 | 20 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 1 | 2 | 3 | |||
| non coding | 1 | |||||
| Total | 0 | 0 | 19 | 12 | 4 |
Variants in ISL1
This is a list of pathogenic ClinVar variants found in the ISL1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 5-51384550-T-A | ISL1-related disorder | Uncertain significance (Jan 17, 2024) | ||
| 5-51384560-A-G | ISL1-related disorder | Likely benign (Nov 24, 2020) | ||
| 5-51384649-C-G | Bladder exstrophy-epispadias-cloacal extrophy complex | Uncertain significance (Sep 30, 2016) | ||
| 5-51387486-A-G | ISL1-related disorder | Likely benign (Oct 18, 2022) | ||
| 5-51387487-C-T | ISL1-related disorder | Likely benign (Jul 12, 2019) | ||
| 5-51387547-G-A | ISL1-related disorder | Likely benign (Jan 13, 2022) | ||
| 5-51387608-C-G | not specified | Uncertain significance (Mar 16, 2022) | ||
| 5-51387615-T-C | not specified | Uncertain significance (May 24, 2024) | ||
| 5-51387616-C-T | ISL1-related disorder | Likely benign (Aug 07, 2019) | ||
| 5-51387638-C-T | not specified | Uncertain significance (May 28, 2023) | ||
| 5-51387665-G-C | not specified | Uncertain significance (Mar 18, 2024) | ||
| 5-51387668-C-T | not specified | Uncertain significance (May 02, 2024) | ||
| 5-51387679-G-T | ISL1-related disorder | Likely benign (Jan 30, 2024) | ||
| 5-51387699-C-G | ISL1-related disorder | Uncertain significance (Jan 25, 2023) | ||
| 5-51387707-C-A | ISL1-related disorder | Likely benign (Jan 28, 2022) | ||
| 5-51387716-C-G | not specified | Uncertain significance (Sep 16, 2021) | ||
| 5-51387730-G-T | ISL1-related disorder | Likely benign (May 18, 2023) | ||
| 5-51389642-G-A | Bladder exstrophy-epispadias-cloacal extrophy complex | Uncertain significance (Sep 30, 2016) | ||
| 5-51389671-A-G | ISL1-related disorder | Benign (Oct 17, 2019) | ||
| 5-51389680-G-A | Benign (Dec 31, 2019) | |||
| 5-51389693-A-G | ISL1-related disorder | Uncertain significance (Aug 23, 2023) | ||
| 5-51389708-A-T | ISL1-related disorder | Uncertain significance (Dec 31, 2023) | ||
| 5-51389734-C-T | Benign (Dec 31, 2019) | |||
| 5-51389749-C-T | ISL1-related disorder | Likely benign (Dec 12, 2022) | ||
| 5-51389789-G-T | ISL1-related disorder • not specified | Uncertain significance (Dec 19, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| ISL1 | protein_coding | protein_coding | ENST00000230658 | 6 | 11644 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.869 | 0.131 | 124752 | 0 | 2 | 124754 | 0.00000802 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.87 | 124 | 198 | 0.625 | 0.00000922 | 2310 |
| Missense in Polyphen | 17 | 63.045 | 0.26965 | 750 | ||
| Synonymous | -1.47 | 89 | 73.0 | 1.22 | 0.00000361 | 656 |
| Loss of Function | 3.17 | 2 | 15.4 | 0.130 | 6.65e-7 | 179 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000646 | 0.0000646 |
| Ashkenazi Jewish | 0.0000993 | 0.0000993 |
| 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:
- Function
- FUNCTION: DNA-binding transcriptional activator. Recognizes and binds to the consensus octamer binding site 5'-ATAATTAA-3' in promoter of target genes. Plays a fundamental role in the gene regulatory network essential for retinal ganglion cell (RGC) differentiation. Cooperates with the transcription factor POU4F2 to achieve maximal levels of expression of RGC target genes and RGC fate specification in the developing retina. Involved in the specification of motor neurons in cooperation with LHX3 and LDB1. Binds to insulin gene enhancer sequences. Essential for heart development. Marker of one progenitor cell population that give rise to the outflow tract, right ventricle, a subset of left ventricular cells, and a large number of atrial cells as well, its function is required for these progenitors to contribute to the heart. Controls the expression of FGF and BMP growth factors in this cell population and is required for proliferation and survival of cells within pharyngeal foregut endoderm and adjacent splanchnic mesoderm as well as for migration of cardiac progenitors into the heart (By similarity). {ECO:0000250|UniProtKB:P61372, ECO:0000250|UniProtKB:P61374}.;
- Pathway
- Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human);Anti-diabetic Drug Potassium Channel Inhibitors Pathway, Pharmacodynamics;Heart Development;Neural Crest Differentiation;Cardiac Progenitor Differentiation;Developmental Biology;Regulation of expression of SLITs and ROBOs;Signaling by ROBO receptors;Axon guidance
(Consensus)
Intolerance Scores
- loftool
- 0.179
- rvis_EVS
- -0.36
- rvis_percentile_EVS
- 28.63
Haploinsufficiency Scores
- pHI
- 0.393
- hipred
- Y
- hipred_score
- 0.851
- ghis
- 0.457
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.987
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Isl1
- Phenotype
- endocrine/exocrine gland 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); growth/size/body region phenotype; craniofacial phenotype; muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; neoplasm; reproductive system phenotype; normal 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); vision/eye phenotype; limbs/digits/tail phenotype; hearing/vestibular/ear 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); digestive/alimentary phenotype; renal/urinary system phenotype; skeleton phenotype;
Zebrafish Information Network
- Gene name
- isl1
- Affected structure
- secondary motor neuron
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;neural crest cell migration;secondary heart field specification;outflow tract septum morphogenesis;outflow tract morphogenesis;endocardial cushion morphogenesis;cardiac right ventricle morphogenesis;regulation of secondary heart field cardioblast proliferation;heart development;positive regulation of cell population proliferation;positive regulation of vascular endothelial growth factor production;positive regulation of epithelial to mesenchymal transition;spinal cord motor neuron cell fate specification;spinal cord motor neuron differentiation;visceral motor neuron differentiation;trigeminal nerve development;pituitary gland development;pancreas development;axon regeneration;retinal ganglion cell axon guidance;positive regulation of insulin secretion;positive regulation of granulocyte macrophage colony-stimulating factor production;positive regulation of interferon-gamma production;positive regulation of interleukin-1 alpha production;positive regulation of interleukin-1 beta production;positive regulation of interleukin-12 production;positive regulation of interleukin-6 production;positive regulation of tumor necrosis factor production;negative regulation of intracellular estrogen receptor signaling pathway;positive regulation of histone acetylation;positive regulation of tyrosine phosphorylation of STAT protein;positive regulation of DNA binding;negative regulation of neuron apoptotic process;positive regulation of cell differentiation;negative regulation of neuron differentiation;positive regulation of angiogenesis;positive regulation of transcription by RNA polymerase II;neuron fate specification;mesenchymal cell differentiation;sensory system development;peripheral nervous system neuron axonogenesis;negative regulation of epithelial cell proliferation;negative regulation of inflammatory response;ventricular cardiac muscle tissue morphogenesis;pharyngeal system development;cardiac muscle cell myoblast differentiation;innervation;atrial septum morphogenesis;cardiac cell fate determination;cellular response to glucocorticoid stimulus;positive regulation of granulocyte colony-stimulating factor production;negative regulation of protein homodimerization activity;negative regulation of canonical Wnt signaling pathway;positive regulation of macrophage colony-stimulating factor production
- Cellular component
- nucleus;nucleoplasm;cytoplasm
- Molecular function
- RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;RNA polymerase II activating transcription factor binding;enhancer sequence-specific DNA binding;DNA-binding transcription activator activity, RNA polymerase II-specific;transcription coactivator activity;protein binding;nuclear receptor binding;estrogen receptor binding;bHLH transcription factor binding;metal ion binding;promoter-specific chromatin binding