ASPM

assembly factor for spindle microtubules

Basic information

Region (hg38): 1:197084121-197146694

Previous symbols: [ "MCPH5" ]

Links

ENSG00000066279 ∙ NCBI:259266 ∙ OMIM:605481 ∙ HGNC:19048 ∙ Uniprot:Q8IZT6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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
• autosomal recessive primary microcephaly (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the ASPM gene.

• not provided (121 variants)
• Microcephaly 5, primary, autosomal recessive (111 variants)
• Inborn genetic diseases (13 variants)
• Microcephaly 1, primary, autosomal recessive (5 variants)
• Autosomal recessive primary microcephaly (4 variants)
• Abnormality of the nervous system (4 variants)
• ASPM-related disorder (3 variants)
• Microcephaly (2 variants)
• Fetal akinesia deformation sequence 1;Arthrogryposis multiplex congenita (1 variants)
• See cases (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.

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			36	213	14	263
missense		1	689	65	13	768
nonsense	86	18		1		105
start loss		1	1			2
frameshift	104	30	3			137
inframe indel			19			19
splice donor/acceptor (+/-2bp)	5	10	1			16
splice region	1	3	17	18	3	42
non coding			14	113	41	168
Total	195	60	763	392	68

Highest pathogenic variant AF is 0.000178

Variants in ASPM

This is a list of pathogenic ClinVar variants found in the ASPM region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-197084166-A-G		not specified • Microcephaly 5, primary, autosomal recessive	Conflicting classifications of pathogenicity (Jul 01, 2023)
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 (Apr 11, 2023)
1-197084342-C-T		Microcephaly 5, primary, autosomal recessive	Conflicting classifications of pathogenicity (Feb 13, 2023)
1-197084343-G-A			Uncertain significance (Jan 08, 2024)
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)
1-197084412-C-A			Uncertain significance (Jul 27, 2023)
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 • Microcephaly 5, primary, autosomal recessive	Benign/Likely benign (Dec 01, 2023)
1-197086795-T-C		not specified • Microcephaly 5, primary, autosomal recessive	Benign (Feb 01, 2024)
1-197086798-C-A			Uncertain significance (Oct 23, 2019)
1-197086798-C-T		Microcephaly 5, primary, autosomal recessive	Conflicting classifications of pathogenicity (Jan 29, 2024)
1-197086804-T-G			Uncertain significance (Apr 18, 2021)

GnomAD

Source: gnomAD

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: 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

	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