ASPM

Chr 1AR

assembly factor for spindle microtubules

NCBI Gene: 259266ENSG00000066279UniProt: Q8IZT6

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

Primary Disease Associations & Inheritance

Microcephaly 5, primary, autosomal recessiveMIM #608716
AR
563
ClinVar variants
81
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ASPM
🧬
Gene-Disease Validity (ClinGen)
autosomal recessive primary microcephaly · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
81 Pathogenic / Likely Pathogenic· 311 VUS of 563 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.74LOEUF
pLI 0.000
Z-score 4.39
OE 0.63 (0.54–0.74)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.74Z-score
OE missense 1.05 (1.01–1.09)
1836 obs / 1749.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.63 (0.54–0.74)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.05 (1.01–1.09)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.17
0≤1.21.6
LoF obs/exp: 105 / 166.1Missense obs/exp: 1836 / 1749.3Syn Z: -3.29

ClinVar Variant Classifications

563 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic63
Likely Pathogenic18
VUS311
Likely Benign169
Benign1
Conflicting1
63
Pathogenic
18
Likely Pathogenic
311
VUS
169
Likely Benign
1
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
47
0
16
0
63
Likely Pathogenic
13
0
5
0
18
VUS
1
305
4
1
311
Likely Benign
0
27
42
100
169
Benign
0
0
1
0
1
Conflicting
—1
Total6133268101563

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ASPM · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

ASPM-related pirmary microcephaly

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Microcephaly 5, primary, autosomal recessive

MIM #608716

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — ASPM
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Predicting potential therapeutic targets and small molecule drugs for early-stage lung adenocarcinoma.
Yu Y et al.·Biomed Pharmacother
2024
High-grade B-cell lymphoma not otherwise specified, with diffuse large B-cell lymphoma gene expression signatures: Genomic analysis and potential therapeutics.
Lone W et al.·Am J Hematol
2025
[Genetic diagnosis of microcephaly].
Liao XF et al.·Zhonghua Fu Chan Ke Za Zhi
2023
ASPM overexpression enhances cellular proliferation and migration and predicts worse prognosis for papillary renal cell carcinoma.
Li N et al.·J Biosci
2023
[Genetic analysis of a child with autosomal recessive primary microcephaly due to variant of ASPM gene and a literature review].
Wang J et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2024Review
RBM10 C761Y mutation induced oncogenic ASPM isoforms and regulated β-catenin signaling in cholangiocarcinoma.
Chang J et al.·J Exp Clin Cancer Res
2024
Detection of genomic variants by genome sequencing in foetuses with central nervous system abnormalities.
Wang Y et al.·Ann Med
2024
What the fruit fly can tell us about autosomal recessive primary microcephaly.
Chakraborty S et al.·Fly (Austin)
2025Review
Discovering potential therapeutic targets in glioblastoma multiforme using a multi-omics approach.
Saeed MU et al.·Pathol Res Pract
2025
ASPM Predicts Poor Clinical Outcome and Promotes Tumorigenesis for Diffuse Large B-cell Lymphoma.
Wu J et al.·Curr Cancer Drug Targets
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Prosta-omics: machine learning-driven TPSA prediction and molecular modeling of ASPM-inhibitors for prostate cancer treatment.
Sahibzada KI et al.·Mol Divers
2026Functional
Mutation screening of the ASPM gene in multiple Pashtun origin MCPH families revealed the recurrent nonsense mutation p.Trp1326*: A step towards the development of a genetic diagnostic test.
Hashmi HB et al.·Neurogenetics
2025
A core stemness-associated module reveals PLK1, NUF2, KIF23, CDCA8, TOP2A, CENPF, AURKA, and ASPM as key genes in rectal cancer.
Yao B et al.·Eur J Med Res
2025🔓 Open Access
RhoA Enhances Schwann Cell Microtubule Dynamics and Myelination via a YAP1/TEAD3/CDK2/ASPM/p60-Katanin Axis.
Ma X et al.·Glia
2026
Comprehensive Analysis Identifies Tumor Mutation Burden-associated Genes ASPM and KIF11 as Novel Biomarkers for Adrenocortical Carcinoma.
Chen JY et al.·Curr Cancer Drug Targets
2025
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools