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GeneBe

ASPM

assembly factor for spindle microtubules

Basic information

Region (hg38): 1:197084120-197146694

Previous symbols: [ "MCPH5" ]

Links

ENSG00000066279NCBI:259266OMIM:605481HGNC:19048Uniprot:Q8IZT6AlphaFoldGenCCjaxSfariGnomADPubmed

Phenotypes

GenCC

Source: genCC

  • 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: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Microcephaly, primary autosomal recessive, 5ARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingNeurologic12355089; 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 ClinVar and linked to the ASPM gene.

  • 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)link
1-197084179-A-C Microcephaly 5, primary, autosomal recessive Uncertain significance (Jan 12, 2018)link
1-197084242-C-T Microcephaly 5, primary, autosomal recessive Uncertain significance (Jan 12, 2018)link
1-197084243-G-A Microcephaly 5, primary, autosomal recessive Benign (Jul 14, 2021)link
1-197084246-G-C not specified Uncertain significance (Feb 08, 2013)link
1-197084263-C-T Microcephaly 5, primary, autosomal recessive Uncertain significance (Jan 13, 2018)link
1-197084264-G-A not specified • Microcephaly 5, primary, autosomal recessive Benign/Likely benign (Jun 26, 2018)link
1-197084342-C-T Microcephaly 5, primary, autosomal recessive Conflicting interpretations of pathogenicity (Sep 24, 2022)link
1-197084384-T-C Likely benign (Aug 16, 2022)link
1-197084388-TC-T Uncertain significance (Jan 12, 2022)link
1-197084394-T-A Uncertain significance (Aug 30, 2022)link
1-197084420-CT-C Likely pathogenic (Oct 04, 2017)link
1-197084423-A-C Likely benign (Aug 21, 2022)link
1-197084431-TA-T Likely benign (Aug 10, 2019)link
1-197084431-T-TA Benign (Aug 10, 2019)link
1-197084439-A-G Likely benign (Aug 22, 2021)link
1-197084463-GTTC-G Likely benign (May 28, 2019)link
1-197086652-T-C Benign (Jun 19, 2018)link
1-197086785-C-T not specified Benign/Likely benign (Sep 27, 2022)link
1-197086795-T-C not specified • Microcephaly 5, primary, autosomal recessive Benign (Nov 04, 2022)link
1-197086798-C-A Uncertain significance (Oct 23, 2019)link
1-197086798-C-T Microcephaly 5, primary, autosomal recessive Conflicting interpretations of pathogenicity (Oct 15, 2022)link
1-197086804-T-G Uncertain significance (Aug 13, 2021)link
1-197086839-A-T Uncertain significance (Jan 27, 2022)link
1-197086846-G-A Inborn genetic diseases Uncertain significance (Jun 16, 2023)link

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
ASPMprotein_codingprotein_codingENST00000367409 2862567
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
3.35e-491.0012480559381257480.00376
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.73618361.75e+31.050.000091022782
Missense in Polyphen460507.50.906416929
Synonymous-3.296825811.170.00002816448
Loss of Function4.391051660.6320.000009972088

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.03490.0346
Ashkenazi Jewish0.0007990.000794
East Asian0.001420.00141
Finnish0.0008880.000878
European (Non-Finnish)0.002080.00206
Middle Eastern0.001420.00141
South Asian0.0009150.000915
Other0.002150.00212

dbNSFP

Source: dbNSFP

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

AllRecessiveDominant
MendelianHighMediumHigh
Primary ImmunodeficiencyHighHighHigh
CancerHighHighHigh

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