ASPM
assembly factor for spindle microtubules
Basic information
Region (hg38): 1:197084120-197146694
Previous symbols: [ "MCPH5" ]
Links
Phenotypes
GenCC
Source:
- microcephaly 5, primary, autosomal recessive (Strong), mode of inheritance: AR
- microcephaly 5, primary, autosomal recessive (Definitive), mode of inheritance: AR
- autosomal recessive primary microcephaly (Supportive), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Microcephaly, primary autosomal recessive, 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 | Neurologic | 12355089; 14574646; 16673149; 18452193; 19353628; 19028728; 19770472 |
| Frequent infections have been described, but it is not clear if these are intrinsic to the disorder or secondary to neurologic manifestations |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (1076 variants)
- Microcephaly 5, primary, autosomal recessive (542 variants)
- not specified (203 variants)
- Inborn genetic diseases (147 variants)
- Intellectual disability (17 variants)
- Primary Microcephaly, Recessive (6 variants)
- Autosomal recessive primary microcephaly (6 variants)
- Microcephaly 1, primary, autosomal recessive (5 variants)
- Microcephaly (5 variants)
- Abnormality of the nervous system (4 variants)
- See cases (2 variants)
- Fetal akinesia deformation sequence 1;Arthrogryposis multiplex congenita (1 variants)
- Arthrogryposis multiplex congenita;Fetal akinesia deformation sequence 1 (1 variants)
- Diastrophic dysplasia (1 variants)
- - (1 variants)
- Microcephaly;Lissencephaly (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the ASPM gene is commonly pathogenic or not.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 43 | 191 | 16 | 250 | ||
| missense | 2 | 585 | 125 | 23 | 735 | |
| nonsense | 89 | 15 | 1 | 105 | ||
| start loss | 0 | |||||
| frameshift | 53 | 25 | 21 | 1 | 100 | |
| inframe indel | 34 | 5 | 1 | 40 | ||
| splice variant | 7 | 10 | 20 | 22 | 2 | 61 |
| non coding | 4 | 13 | 108 | 41 | 166 | |
| Total | 187 | 57 | 683 | 448 | 82 |
Highest pathogenic variant AF is 0.000178
Variants in ASPM
This is a list of pathogenic ClinVar variants found in the ASPM region.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 1-197084166-A-G | not specified • Microcephaly 5, primary, autosomal recessive | Conflicting interpretations of pathogenicity (Jul 15, 2018) | ||
| 1-197084179-A-C | Microcephaly 5, primary, autosomal recessive | Uncertain significance (Jan 12, 2018) | ||
| 1-197084242-C-T | Microcephaly 5, primary, autosomal recessive | Uncertain significance (Jan 12, 2018) | ||
| 1-197084243-G-A | Microcephaly 5, primary, autosomal recessive | Benign (Jul 14, 2021) | ||
| 1-197084246-G-C | not specified | Uncertain significance (Feb 08, 2013) | ||
| 1-197084263-C-T | Microcephaly 5, primary, autosomal recessive | Uncertain significance (Jan 13, 2018) | ||
| 1-197084264-G-A | not specified • Microcephaly 5, primary, autosomal recessive | Benign/Likely benign (Jun 26, 2018) | ||
| 1-197084342-C-T | Microcephaly 5, primary, autosomal recessive | Conflicting interpretations of pathogenicity (Sep 24, 2022) | ||
| 1-197084384-T-C | Likely benign (Aug 16, 2022) | |||
| 1-197084388-TC-T | Uncertain significance (Jan 12, 2022) | |||
| 1-197084394-T-A | Uncertain significance (Aug 30, 2022) | |||
| 1-197084420-CT-C | Likely pathogenic (Oct 04, 2017) | |||
| 1-197084423-A-C | Likely benign (Aug 21, 2022) | |||
| 1-197084431-TA-T | Likely benign (Aug 10, 2019) | |||
| 1-197084431-T-TA | Benign (Aug 10, 2019) | |||
| 1-197084439-A-G | Likely benign (Aug 22, 2021) | |||
| 1-197084463-GTTC-G | Likely benign (May 28, 2019) | |||
| 1-197086652-T-C | Benign (Jun 19, 2018) | |||
| 1-197086785-C-T | not specified | Benign/Likely benign (Sep 27, 2022) | ||
| 1-197086795-T-C | not specified • Microcephaly 5, primary, autosomal recessive | Benign (Nov 04, 2022) | ||
| 1-197086798-C-A | Uncertain significance (Oct 23, 2019) | |||
| 1-197086798-C-T | Microcephaly 5, primary, autosomal recessive | Conflicting interpretations of pathogenicity (Oct 15, 2022) | ||
| 1-197086804-T-G | Uncertain significance (Aug 13, 2021) | |||
| 1-197086839-A-T | Uncertain significance (Jan 27, 2022) | |||
| 1-197086846-G-A | Inborn genetic diseases | Uncertain significance (Jun 16, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| ASPM | protein_coding | protein_coding | ENST00000367409 | 28 | 62567 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 3.35e-49 | 1.00 | 124805 | 5 | 938 | 125748 | 0.00376 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -0.736 | 1836 | 1.75e+3 | 1.05 | 0.0000910 | 22782 |
| Missense in Polyphen | 460 | 507.5 | 0.90641 | 6929 | ||
| Synonymous | -3.29 | 682 | 581 | 1.17 | 0.0000281 | 6448 |
| Loss of Function | 4.39 | 105 | 166 | 0.632 | 0.00000997 | 2088 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0349 | 0.0346 |
| Ashkenazi Jewish | 0.000799 | 0.000794 |
| East Asian | 0.00142 | 0.00141 |
| Finnish | 0.000888 | 0.000878 |
| European (Non-Finnish) | 0.00208 | 0.00206 |
| Middle Eastern | 0.00142 | 0.00141 |
| South Asian | 0.000915 | 0.000915 |
| Other | 0.00215 | 0.00212 |
dbNSFP
Source:
- Function
- FUNCTION: Involved in mitotic spindle regulation and coordination of mitotic processes. The function in regulating microtubule dynamics at spindle poles including spindle orientation, astral microtubule density and poleward microtubule flux seems to depend on the association with the katanin complex formed by KATNA1 and KATNB1. Enhances the microtubule lattice severing activity of KATNA1 by recruiting the katanin complex to microtubules. Can block microtubule minus-end growth and reversely this function can be enhanced by the katanin complex (PubMed:28436967). May have a preferential role in regulating neurogenesis. {ECO:0000269|PubMed:12355089, ECO:0000269|PubMed:15972725, ECO:0000269|PubMed:28436967}.;
- Disease
- DISEASE: Microcephaly 5, primary, autosomal recessive (MCPH5) [MIM:608716]: A disease defined as a head circumference more than 3 standard deviations below the age-related mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. Despite this marked reduction in size, the gyral pattern is relatively well preserved, with no major abnormality in cortical architecture. Affected individuals are mentally retarded. Primary microcephaly is further defined by the absence of other syndromic features or significant neurological deficits due to degenerative brain disorder. {ECO:0000269|PubMed:12355089, ECO:0000269|PubMed:14574646, ECO:0000269|PubMed:22989186}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.0867
Intolerance Scores
- loftool
- 0.984
- rvis_EVS
- 1.76
- rvis_percentile_EVS
- 96.74
Haploinsufficiency Scores
- pHI
- 0.344
- hipred
- N
- hipred_score
- 0.347
- ghis
- 0.637
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- H
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.650
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | Medium | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |
Mouse Genome Informatics
- Gene name
- Aspm
- Phenotype
- homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; immune system 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); hematopoietic system phenotype; reproductive system phenotype;
Zebrafish Information Network
- Gene name
- aspm
- Affected structure
- head
- Phenotype tag
- abnormal
- Phenotype quality
- decreased size
Gene ontology
- Biological process
- neuron migration;positive regulation of neuroblast proliferation;spindle organization;spermatogenesis;male gonad development;forebrain neuroblast division;cerebral cortex development;negative regulation of neuron differentiation;negative regulation of asymmetric cell division;oogenesis;developmental growth;regulation of meiotic cell cycle;spindle localization;maintenance of centrosome location;positive regulation of canonical Wnt signaling pathway;spindle assembly involved in meiosis;neuronal stem cell population maintenance
- Cellular component
- nucleus;cytoplasm;centrosome;apical plasma membrane;midbody;microtubule minus-end;meiotic spindle;mitotic spindle pole
- Molecular function
- calmodulin binding;protein kinase binding