ASPM

Chr 1

assembly factor for spindle microtubules

Also known as: ASP, Calmbp1, MCPH5

NCBI Gene: 259266 ENSG00000066279 UniProt: Q8IZT6

ASPM encodes a protein essential for normal mitotic spindle function in neuroblasts, with a preferential role in regulating neurogenesis during brain development. Mutations cause primary microcephaly type 5, an autosomal recessive disorder characterized by severely reduced brain size. The pathogenic mechanism involves gain-of-function effects that disrupt normal spindle regulation during neuronal cell division.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene is the human ortholog of the Drosophila melanogaster 'abnormal spindle' gene (asp), which is essential for normal mitotic spindle function in embryonic neuroblasts. Studies in mouse also suggest a role of this gene in mitotic spindle regulation, with a preferential role in regulating neurogenesis. Mutations in this gene are associated with microcephaly primary type 5. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2011]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtMicrocephaly 5, primary, autosomal recessive

Clinical highlights

Gene-disease validity (ClinGen)

autosomal recessive primary microcephaly · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.74

LOEUF

LOF

Mechanism· G2P

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GeneReview available — ASPM