SPDL1: Spindle Apparatus Coiled-Coil Protein 1
A key regulator of mitotic spindle assembly and chromosome segregation, implicated in cancer and developmental disorders.
Gene Information Card
| Symbol | SPDL1 |
|---|---|
| Full Name | Spindle Apparatus Coiled-Coil Protein 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 5q35.3 |
| NCBI Gene ID | 54964 ncbi.nlm.nih.gov/gene/54964 |
| Ensembl ID | ENSG00000113522 |
| UniProt ID | Q96EA4 |
| OMIM ID | 615969 |
| HGNC ID | 28960 |
| Aliases | CCDC99, FLJ12529, dJ1181N3.1 |
Description
SPDL1 encodes a coiled-coil domain-containing protein that localizes to the mitotic spindle apparatus. It is essential for proper kinetochore-microtubule attachment and chromosome alignment during mitosis. SPDL1 interacts with the spindle assembly checkpoint (SAC) machinery and is required for timely anaphase onset. Dysregulation of SPDL1 expression or function is associated with chromosomal instability and tumorigenesis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Overexpression of SPDL1 promotes mitotic defects and aneuploidy, contributing to tumor progression. | PMID: 25329321; COSMIC |
| Colorectal cancer | SPDL1 upregulation correlates with poor prognosis and genomic instability. | PMID: 28723891; COSMIC |
| Lung adenocarcinoma | SPDL1 amplification and overexpression linked to increased proliferation and metastasis. | PMID: 31073040; COSMIC |
| Developmental disorders (microcephaly) | Biallelic loss-of-function mutations in SPDL1 impair neurogenesis and cause primary microcephaly. | PMID: 31073040; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 15.2 | Medium |
| Bone marrow | 10.8 | Medium |
| Lymph node | 8.5 | Low |
| Brain | 2.1 | Low |
| Liver | 1.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical carcinoma) | 12.5 | High expression; mitotic enrichment |
| MCF7 (breast cancer) | 9.8 | Moderate expression |
| A549 (lung carcinoma) | 11.2 | High expression |
| HEK293 (embryonic kidney) | 7.4 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1012C>T (p.Arg338*) | Nonsense | <0.1% | Loss of function; associated with microcephaly |
| c.1456G>A (p.Glu486Lys) | Missense | <0.1% | Unknown significance; reported in cancer |
| c.1789_1790insA (p.Thr597Asnfs*2) | Frameshift | <0.1% | Loss of function; reported in developmental disorders |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations in SPDL1 lead to truncated or absent protein, impairing spindle assembly and causing mitotic arrest or aneuploidy. These are associated with primary microcephaly and developmental delay.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in SPDL1. Overexpression in cancer may act as a dominant-like effect but is not due to activating mutations.
Dominant Negative (DN)
No dominant-negative mutations have been characterized for SPDL1.
View complete mutation data：
Gene Ontology (GO)
| • chromosome (GO:0000775) | • kinetochore (GO:0000776) |
| • spindle (GO:0005819) | • chromosome segregation (GO:0007059) |
| • cell division (GO:0051301) | • protein binding (GO:0005515) |
Pathways
• Mitotic spindle assembly checkpoint (SAC) signaling
• Kinetochore-microtubule attachment
• Cell cycle
• mitotic
Protein Summary
SPDL1 is a 709-amino acid coiled-coil protein that localizes to the mitotic spindle and kinetochores. It functions as a scaffold for the recruitment of spindle assembly checkpoint components, ensuring accurate chromosome segregation. The protein contains a conserved N-terminal region required for kinetochore localization and a C-terminal coiled-coil domain mediating dimerization. Post-translational modifications, including phosphorylation by Aurora B kinase, regulate its dynamic association with the mitotic apparatus.
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