IQSEC2
Basic information
Region (hg38): X:53225827-53321350
Previous symbols: [ "MRX1", "MRX78", "MRX18" ]
Links
Phenotypes
GenCC
Source:
- intellectual disability, X-linked 1 (Definitive), mode of inheritance: XLD
- non-syndromic X-linked intellectual disability (Supportive), mode of inheritance: XL
- severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome (Supportive), mode of inheritance: XL
- intellectual disability, X-linked 1 (Strong), mode of inheritance: XL
- intellectual disability, X-linked 1 (Definitive), mode of inheritance: XL
- X-linked complex neurodevelopmental disorder (Definitive), mode of inheritance: XL
Clinical Genomic Database
Source:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Intellectual developmental disorder, X-linked 1 | 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 | Neurologic | 7943039; 3177466; 20473311 |
ClinVar
This is a list of variants' phenotypes submitted to
- Intellectual disability, X-linked 1 (756 variants)
- not provided (311 variants)
- Inborn genetic diseases (104 variants)
- not specified (81 variants)
- See cases (7 variants)
- Intellectual disability (6 variants)
- IQSEC2-related condition (4 variants)
- Tip-toe gait (2 variants)
- Neurodevelopmental disorder (2 variants)
- Seizure (2 variants)
- Abnormal brain morphology (1 variants)
- Neurodevelopmental delay (1 variants)
- Autism spectrum disorder (1 variants)
- Specific learning disability (1 variants)
- Undetermined early-onset epileptic encephalopathy (1 variants)
- Paraplegia-intellectual disability-hyperkeratosis syndrome (1 variants)
- Intellectual developmental disorder, X-linked 108 (1 variants)
- IQSEC2-related X-linked neurodevelopmental disorder (1 variants)
- Specific learning disability;Involuntary movements (1 variants)
- Severe intellectual deficiency (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the IQSEC2 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 | 237 | 27 | 275 | ||
missense | 12 | 314 | 47 | 16 | 394 | |
nonsense | 37 | 46 | ||||
start loss | 0 | |||||
frameshift | 69 | 11 | 81 | |||
inframe indel | 11 | |||||
splice donor/acceptor (+/-2bp) | 10 | 17 | ||||
splice region ? | 3 | 11 | 11 | 3 | 28 | |
non coding ? | 61 | 29 | 95 | |||
Total | 118 | 44 | 338 | 346 | 73 |
Highest pathogenic variant AF is 0.00000907
Variants in IQSEC2
This is a list of pathogenic ClinVar variants found in the IQSEC2 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-53227827-C-T | Likely benign (Jun 01, 2023) | |||
X-53234206-C-G | not specified | Likely benign (Mar 18, 2016) | ||
X-53234221-A-T | Uncertain significance (Dec 05, 2019) | |||
X-53234223-A-G | Likely pathogenic (Aug 23, 2019) | |||
X-53234227-C-T | Intellectual disability, X-linked 1 | Uncertain significance (Sep 15, 2021) | ||
X-53234228-G-A | Likely benign (Apr 09, 2018) | |||
X-53234229-G-A | Intellectual disability, X-linked 1 | Uncertain significance (Feb 04, 2022) | ||
X-53234231-G-A | Intellectual disability, X-linked 1 | Likely benign (Oct 26, 2022) | ||
X-53234238-C-T | Intellectual disability, X-linked 1 | Uncertain significance (Oct 04, 2023) | ||
X-53234240-G-A | Intellectual disability, X-linked 1 | Likely benign (May 15, 2023) | ||
X-53234247-T-TTGGCC | Intellectual disability, X-linked 1 | Pathogenic (Jul 31, 2017) | ||
X-53234252-CT-C | Uncertain significance (May 07, 2023) | |||
X-53234256-G-A | Intellectual disability, X-linked 1 | Uncertain significance (Aug 17, 2023) | ||
X-53234266-TG-T | Intellectual disability, X-linked 1 | Pathogenic (May 04, 2022) | ||
X-53234266-T-TG | Intellectual disability, X-linked 1 | Pathogenic (Jun 25, 2023) | ||
X-53234267-G-T | Intellectual disability, X-linked 1 | Likely benign (Nov 03, 2023) | ||
X-53234268-G-A | Intellectual disability, X-linked 1 | Conflicting classifications of pathogenicity (Jan 01, 2024) | ||
X-53234267-G-GGGGGGGTTGGCTGTGCC | Intellectual disability, X-linked 1 | Pathogenic (Jan 23, 2020) | ||
X-53234270-G-A | not specified | Uncertain significance (Aug 12, 2014) | ||
X-53234275-T-TG | Intellectual disability, X-linked 1 | Pathogenic (Nov 22, 2022) | ||
X-53234278-C-T | not specified • Intellectual disability, X-linked 1 • Inborn genetic diseases | Benign (Jan 29, 2024) | ||
X-53234279-T-C | Intellectual disability, X-linked 1 | Likely benign (Dec 18, 2021) | ||
X-53234295-G-C | Intellectual disability, X-linked 1 | Uncertain significance (May 16, 2022) | ||
X-53234296-A-G | Intellectual disability, X-linked 1 | Uncertain significance (Aug 23, 2022) | ||
X-53234299-C-T | Intellectual disability, X-linked 1 | Uncertain significance (Mar 25, 2024) |
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
IQSEC2 | protein_coding | protein_coding | ENST00000396435 | 15 | 88465 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
1.00 | 0.0000155 | 124418 | 0 | 1 | 124419 | 0.00000402 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 5.19 | 241 | 598 | 0.403 | 0.0000515 | 9587 |
Missense in Polyphen | 48 | 184.28 | 0.26047 | 2482 | ||
Synonymous | 1.91 | 210 | 248 | 0.845 | 0.0000204 | 3186 |
Loss of Function | 5.37 | 1 | 35.6 | 0.0281 | 0.00000282 | 577 |
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) | 0.0000123 | 0.00000888 |
Middle Eastern | 0.00 | 0.00 |
South Asian | 0.00 | 0.00 |
Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Is a guanine nucleotide exchange factor for the ARF GTP- binding proteins. {ECO:0000269|PubMed:26793055}.;
- Pathway
- Endocytosis - Homo sapiens (human)
(Consensus)
Recessive Scores
- pRec
- 0.0922
Intolerance Scores
- loftool
- 0.228
- rvis_EVS
- -0.52
- rvis_percentile_EVS
- 21.2
Haploinsufficiency Scores
- pHI
- 0.711
- hipred
- Y
- hipred_score
- 0.617
- ghis
- 0.551
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.328
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Iqsec2
- Phenotype
Gene ontology
- Biological process
- actin cytoskeleton organization;regulation of ARF protein signal transduction;modulation of chemical synaptic transmission;regulation of neurotransmitter receptor localization to postsynaptic specialization membrane
- Cellular component
- cytoplasm;Schaffer collateral - CA1 synapse
- Molecular function
- ARF guanyl-nucleotide exchange factor activity