ISCA1
Basic information
Region (hg38): 9:86264546-86283102
Previous symbols: [ "HBLD2" ]
Links
Phenotypes
GenCC
Source:
- multiple mitochondrial dysfunctions syndrome 5 (Strong), mode of inheritance: AR
- multiple mitochondrial dysfunctions syndrome 5 (Limited), mode of inheritance: AR
- multiple mitochondrial dysfunctions syndrome 5 (Strong), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Multiple mitochondrial dysfunctions syndrome 5 | AR | 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; Variants may additionally act as susceptibility factors (rather than being involved in Mendelian-inherited dominant disease) | Biochemical; Musculoskeletal; Neurologic; Ophthalmologic | 28356563; 29767723 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (27 variants)
- not_specified (4 variants)
- Multiple_mitochondrial_dysfunctions_syndrome_5 (3 variants)
- Fatal_multiple_mitochondrial_dysfunctions_syndrome (1 variants)
- ISCA1-related_disorder (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the ISCA1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000030940.4. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 8 | |||||
| missense | 14 | 16 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 1 | 1 | 14 | 8 | 0 |
Highest pathogenic variant AF is 0.00000995219
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| ISCA1 | protein_coding | protein_coding | ENST00000375991 | 4 | 18216 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.171 | 0.776 | 125645 | 0 | 3 | 125648 | 0.0000119 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.784 | 47 | 64.7 | 0.726 | 0.00000292 | 821 |
| Missense in Polyphen | 7 | 16.113 | 0.43444 | 235 | ||
| Synonymous | 0.462 | 21 | 23.9 | 0.880 | 0.00000109 | 254 |
| Loss of Function | 1.59 | 2 | 6.32 | 0.316 | 3.50e-7 | 80 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000266 | 0.0000264 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Involved in the maturation of mitochondrial 4Fe-4S proteins functioning late in the iron-sulfur cluster assembly pathway. Probably involved in the binding of an intermediate of Fe/S cluster assembly. {ECO:0000269|PubMed:15262227, ECO:0000269|PubMed:22323289}.;
- Pathway
- Mitochondrial iron-sulfur cluster biogenesis;Metabolism
(Consensus)
Recessive Scores
- pRec
- 0.113
Intolerance Scores
- loftool
- 0.517
- rvis_EVS
- 0.08
- rvis_percentile_EVS
- 59.43
Haploinsufficiency Scores
- pHI
- 0.281
- hipred
- N
- hipred_score
- 0.413
- ghis
- 0.648
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.539
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Isca1
- 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); embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; growth/size/body region phenotype;
Zebrafish Information Network
- Gene name
- isca1
- Affected structure
- nucleate erythrocyte
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- iron-sulfur cluster assembly;small molecule metabolic process;protein maturation by iron-sulfur cluster transfer
- Cellular component
- mitochondrion;mitochondrial matrix
- Molecular function
- structural molecule activity;metal ion binding;2 iron, 2 sulfur cluster binding