SPAG5

Summary

SPAG5 (sperm associated antigen 5, HGNC:13452) is a protein-coding gene on chromosome 17q11.2, encoding Sperm-associated antigen 5 (Q96R06). Essential component of the mitotic spindle required for normal chromosome segregation and progression into anaphase. It is a selective cancer dependency (DepMap: 33.7% of cell lines).

This gene encodes a protein associated with the mitotic spindle apparatus. The encoded protein may be involved in the functional and dynamic regulation of mitotic spindles.

Source: NCBI Gene 10615 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 182 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 33.7% of screened cell lines
• MANE Select transcript: NM_006461

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13452
Approved symbol	SPAG5
Name	sperm associated antigen 5
Location	17q11.2
Locus type	gene with protein product
Status	Approved
Aliases	DEEPEST, MAP126, hMAP126
Ensembl gene	ENSG00000076382
Ensembl biotype	protein_coding
OMIM	615562
Entrez	10615

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 11 protein_coding, 7 retained_intron, 5 nonsense_mediated_decay

ENST00000321765, ENST00000378976, ENST00000536674, ENST00000577259, ENST00000578230, ENST00000578479, ENST00000580083, ENST00000580377, ENST00000580406, ENST00000580567, ENST00000580676, ENST00000580682, ENST00000581133, ENST00000582076, ENST00000582175, ENST00000584206, ENST00000910606, ENST00000910607, ENST00000915050, ENST00000915051, ENST00000915052, ENST00000915053, ENST00000915054

RefSeq mRNA: 1 — MANE Select: NM_006461 NM_006461

CCDS: CCDS32594

Canonical transcript exons

ENST00000321765 — 24 exons

Exon	Start	End
ENSE00000866316	28585534	28585653
ENSE00001671047	28598896	28599025
ENSE00002342450	28598510	28598635
ENSE00002427960	28591982	28593066
ENSE00002697057	28577574	28577770
ENSE00003472506	28579751	28579837
ENSE00003491774	28591698	28591872
ENSE00003528277	28584150	28584252
ENSE00003599990	28584333	28584480
ENSE00003621103	28580009	28580120
ENSE00003647375	28583853	28583986
ENSE00003660503	28579365	28579485
ENSE00003690055	28583511	28583649
ENSE00003702881	28586425	28586499
ENSE00003703065	28585102	28585215
ENSE00003704580	28586090	28586182
ENSE00003704997	28578010	28578090
ENSE00003705480	28578373	28578528
ENSE00003709063	28578218	28578292
ENSE00003709090	28579141	28579252
ENSE00003709268	28584652	28584745
ENSE00003709381	28585864	28585998
ENSE00003709397	28585319	28585411
ENSE00003711256	28578672	28578752

Expression profiles

Bgee: expression breadth ubiquitous, 208 present calls, max score 97.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.0160 / max 452.2007, expressed in 1528 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165039	20.9147	1468
165040	0.9286	165
165038	0.1398	55
165037	0.0176	3
165036	0.0109	2
208109	0.0045	1

Top tissues by expression

284 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	97.79	gold quality
right testis	UBERON:0004534	97.67	gold quality
ventricular zone	UBERON:0003053	97.00	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.88	gold quality
ganglionic eminence	UBERON:0004023	95.61	gold quality
testis	UBERON:0000473	95.50	gold quality
mucosa of transverse colon	UBERON:0004991	92.86	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.70	gold quality
embryo	UBERON:0000922	91.22	gold quality
lower esophagus mucosa	UBERON:0035834	91.06	gold quality
right lobe of liver	UBERON:0001114	90.77	gold quality
right lobe of thyroid gland	UBERON:0001119	89.07	gold quality
adult mammalian kidney	UBERON:0000082	88.73	gold quality
right frontal lobe	UBERON:0002810	88.50	gold quality
left lobe of thyroid gland	UBERON:0001120	87.34	gold quality
rectum	UBERON:0001052	87.16	gold quality
sural nerve	UBERON:0015488	86.47	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.07	gold quality
stromal cell of endometrium	CL:0002255	85.98	gold quality
bone marrow	UBERON:0002371	85.98	gold quality
thyroid gland	UBERON:0002046	85.88	gold quality
small intestine Peyer’s patch	UBERON:0003454	85.73	gold quality
cerebellar hemisphere	UBERON:0002245	85.04	gold quality
sperm	CL:0000019	85.00	gold quality
adrenal tissue	UBERON:0018303	84.90	gold quality
trabecular bone tissue	UBERON:0002483	84.82	gold quality
cerebellar cortex	UBERON:0002129	84.73	gold quality
cingulate cortex	UBERON:0003027	84.63	gold quality
anterior cingulate cortex	UBERON:0009835	84.45	gold quality
metanephros cortex	UBERON:0010533	84.41	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ENAD-17	yes	727.49
E-ANND-3	yes	5.22

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PAX6

miRNA regulators (miRDB)

13 targeting SPAG5, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-657	99.48	66.02	848
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-583	98.71	67.44	1791
HSA-MIR-5572	98.55	65.84	970
HSA-MIR-6881-5P	98.16	67.38	665
HSA-MIR-6511B-5P	97.98	65.64	823
HSA-MIR-6811-5P	97.98	64.96	848
HSA-MIR-3665	97.73	65.08	975
HSA-MIR-8057	97.64	66.54	897
HSA-MIR-6855-5P	97.51	66.03	830
HSA-MIR-6835-5P	95.81	64.27	500
HSA-MIR-5681B	94.82	69.30	514
HSA-MIR-6732-5P	93.97	64.65	422

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 33.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• hMap126 is abundantly expressed in testis and localized in mitotic spindle and may be involved in the functional and dynamic regulation of mitotic spindles. (PMID:11549262)
• These findings suggest that the silencing of astrin induce a p53-dependent apoptosis and has an additive effect on paclitaxel treatment. (PMID:16546135)
• a model is proposed wherein hNinein regulates the dynamic movement of Astrin throughout the cell cycle and this interaction, in turn, is required for maintenance of centrosome/spindle pole integrity. (PMID:17383637)
• Results report that depletion of the microtubule and kinetochore protein astrin results in checkpoint-arrested cells with multipolar spindles and separated sister chromatids, which is consistent with untimely separase activation. (PMID:17664331)
• GSK3beta interacts with and phosphorylates the spindle-associated protein Astrin, resulting in targeting Astrin to the spindle microtubules and kinetochores. (PMID:18055457)
• Astrin acts upstream of Aurora-A to regulate its mitotic spindle localization. (PMID:18361916)
• Results suggest that SNM1B/Apollo and Astrin function together to enforce the prophase checkpoint in response to spindle stress. (PMID:19197158)
• Data show that CLASP1-astrin-Kif2b complex acts as a central switch at kinetochores that defines mitotic progression and promotes fidelity by temporally regulating kinetochore-microtuble attachments. (PMID:20852589)
• The rsults of this study the increased expression of this gene may play a pathogenic role durin testicular development in subjects with DS and cryptorchidism. (PMID:22773063)
• Study identifies astrin as an essential negative mTORC1 regulator in the cellular stress response. Upon stress, astrin inhibits mTORC1 association and recruits the mTORC1 component raptor to stress granules, thereby preventing mTORC1-hyperactivation-induced apoptosis. (PMID:23953116)
• SPAG5 upregulation relates to poor prognosis in cervical cancer patients, and SPAG5 is a regulator of mTOR activity during taxol treatment in cervical cancer. (PMID:24853425)
• Astrin acts as a mitotic phosphoprotein during the regulation of mitosis. (PMID:25009111)
• Results showed a progression-driving role of SPAG5 in prostate cancer which can be regulated by miR-539. (PMID:27037000)
• Molecular requirements for the inter-subunit interaction and kinetochore recruitment of SKAP and Astrin have been reported. (PMID:27095104)
• Low SPAG5 expression is associated with low chemotherapy sensitivity in breast cancer. (PMID:27312051)
• Mechanistically, Plk1 acts as an upstream kinase for Astrin phosphorylation by Cdk1 and targeting phospho-Astrin to KTs, leading to the recruitment of outer KT components, such as Cenp-E, and the stable attachment of spindles to KTs. (PMID:27325694)
• findings reveal a direct physical link between two important regulators of mitotic progression and demonstrate the critical role of the NuMA-Astrin interaction for accurate cell division. (PMID:27462074)
• Data show that aurora-B regulates end-on conversion in human cells and indicate a late role for SPAG5 protein (Astrin)-SKAP complex in the end-on conversion process. (PMID:28751710)
• The authors show that the Astrin-SKAP complex binds synergistically to microtubules with the Ndc80 complex to form an integrated interface. (PMID:28841134)
• MSI2 expression is increased in epithelial cells adjacent to breast carcinoma, and increases with increasing proximity. (PMID:29093438)
• The importance of the SPAG5/AKT-mTOR/Wnt3 axis identified in BUC cell models. (PMID:29662193)
• Data show that increased expression of SPAG5 in hepatocellular carcinoma (HCC) was closely correlated with poor outcomes, indicating that SPAG5 serves a promising prognostic factor in HCC, and functions as an oncogene via CEP55-mediated PI3K/AKT pathway. (PMID:30089483)
• we report the differential SPAG5 expression at both the protein and mRNA levels in Hepatocellular Carcinoma. SPAG5 may be considered a new prognostic marker for Hepatocellular Carcinoma patients, and targeting SPAG5 could provide new treatment strategies for Hepatocellular Carcinoma. (PMID:30157168)
• miR-1179 inhibits the growth and invasion of non-small cell lung cancer cells by targeting SPAG5 and inhibiting Akt (PMID:30180955)
• our data provide a novel evidence for the biological and clinical significance of SPAG5 as a potential biomarker, and we demonstrate that SPAG5-b-catenin-SCARA5 might be a novel pathway involved in hepatocellular carcinoma progression. (PMID:30249289)
• SPAG5 was upregulated in triple-negative breast cancer tissues and that high SPAG5 expression was associated with high risk of local recurrence and poorer outcomes in triple-negative breast cancer patients. SPAG5 functioned as an oncogenic gene in triple-negative breast cancer by interacting with MYCBP and increasing c-MYC transcriptional activity. (PMID:30736840)
• High expression of SPAG5 sustains the malignant growth and invasion of breast cancer cells through the activation of Wnt/beta-catenin signalling (PMID:30854682)
• SPAG5 promotes the progression of GC via enhancing the Wnt/beta-catenin/Survivin axis. (PMID:30904482)
• SPAG5 is upregulated in lung adenocarcinoma. SPAG5 knockdown suppresses proliferation, colony forming, and migration. SPAG5 is regulated in a p53-and p21-dependent manner. (PMID:30955859)
• SPAG5 could be used as an independent prognostic and predictive biomarker that might have clinical utility, especially in ER+ breast cancer patients who received hormonal therapy (PMID:31690268)
• MicroRNA-367-3p overexpression represses the proliferation and invasion of cervical cancer cells through downregulation of SPAG5-mediated Wnt/beta-catenin signalling. (PMID:31792998)
• Expression, immune infiltration and clinical significance of SPAG5 in hepatocellular carcinoma: A gene expression-based study. (PMID:31860771)
• SPAG5-AS1 inhibited autophagy and aggravated apoptosis of podocytes via SPAG5/AKT/mTOR pathway. (PMID:31957155)
• High expression of sperm-associated antigen 5 correlates with poor survival in ovarian cancer. (PMID:31985007)
• SPAG5: An Emerging Oncogene. (PMID:32291236)
• Micro RNA-363 inhibits esophageal squamous cell carcinoma progression by directly targeting sperm-associated antigen 5. (PMID:32586155)
• SPAG5 promotes osteosarcoma metastasis via activation of FOXM1/MMP2 axis. (PMID:32668328)
• Investigation of the SPAG5 gene expression and amplification related to the NuMA mRNA levels in breast ductal carcinoma. (PMID:32838814)
• MiR-133a-3p attenuates resistance of non-small cell lung cancer cells to gefitinib by targeting SPAG5. (PMID:34057242)
• CircFOXM1 promotes proliferation and metastasis of hepatocellular carcinoma via regulating miR-1179/SPAG5 axis. (PMID:34903799)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Spag5	ENSMUSG00000002055
rattus_norvegicus	Spag5	ENSRNOG00000011777

Protein

Protein identifiers

Sperm-associated antigen 5 — Q96R06 (reviewed: Q96R06)

Alternative names: Astrin, Deepest, Mitotic spindle-associated protein p126

All UniProt accessions (9): Q96R06, F5GZT2, J3KSV2, J3KTQ0, J3QRL6, J3QRV8, J3QS12, K7ELC8, K7ELG0

UniProt curated annotations — full annotation on UniProt →

Function. Essential component of the mitotic spindle required for normal chromosome segregation and progression into anaphase. Required for chromosome alignment, normal timing of sister chromatid segregation, and maintenance of spindle pole architecture. In complex with SKAP, promotes stable microtubule-kinetochore attachments. May contribute to the regulation of separase activity. May regulate AURKA localization to mitotic spindle, but not to centrosomes and CCNB1 localization to both mitotic spindle and centrosomes. Involved in centriole duplication. Required for CDK5RAP2, CEP152, WDR62 and CEP63 centrosomal localization and promotes the centrosomal localization of CDK2. In non-mitotic cells, upon stress induction, inhibits mammalian target of rapamycin complex 1 (mTORC1) association and recruits the mTORC1 component RPTOR to stress granules (SGs), thereby preventing mTORC1 hyperactivation-induced apoptosis. May enhance GSK3B-mediated phosphorylation of other substrates, such as MAPT/TAU.

Subunit / interactions. Homodimer, with a globular head domain and a long stalk. Homooligomer; the globular head domains associate, resulting in aster-like structures. Binds to microtubules in the mitotic spindle. Interacts with DCLRE1B/Apollo. Part of an astrin (SPAG5)-kinastrin (SKAP) complex containing KNSTRN, SPAG5, PLK1, DYNLL1 and SGO2. Interacts with KNSTRN. Interacts with RPTOR; this interaction competes with RPTOR binding to MTOR, resulting in decreased mTORC1 formation. Interacts with G3BP1. The complex formed with G3BP1 AND RPTOR is increased by oxidative stress. Interacts with OSBPL8, PCM1 and CDK5RAP2. Interacts (via C-terminus) with NUMA1 (via C-terminus); this interaction promotes the recruitment of SPAG5 to the microtubules at spindle poles in a dynein-dynactin-dependent manner. Interacts with DYNLL1.

Subcellular location. Cytoplasm. Cytoskeleton. Spindle. Spindle pole. Chromosome. Centromere. Kinetochore. Midbody. Microtubule organizing center. Centrosome. Cytoplasmic granule. Centriolar satellite.

Tissue specificity. Highly expressed in testis. Detected at low levels in placenta, liver, pancreas, thymus and colon.

Post-translational modifications. Phosphorylated by AURKA.

Induction. Expression is cell cycle-regulated, with an increase from prophase to cytokinesis and return to basal levels at the next G1 phase.

RefSeq proteins (1): NP_006452* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028728	Astrin	Family

UniProt features (36 total): modified residue 16, sequence conflict 6, region of interest 4, mutagenesis site 4, coiled-coil region 3, compositionally biased region 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96R06-F1	63.81	0.34

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (16): 12, 14, 43, 62, 66, 111, 135, 159, 334, 336, 341, 353, 362, 937, 974, 978

Mutagenesis-validated functional residues (4):

Position	Phenotype
111	decreased phosphorylation by gsk3-beta. partial loss of spindle association; when associated with a-937, a974 and a-978.
937	decreased phosphorylation by gsk3-beta. partial loss of spindle association; when associated with a-111, a974 and a-978.
974	decreased phosphorylation by gsk3-beta; when associated with a-978. partial loss of spindle association; when associated
978	decreased phosphorylation by gsk3-beta; when associated with a-97a. partial loss of spindle association; when associated

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 349 (showing top): GOBP_CHROMOSOME_ORGANIZATION, GOBP_ESTABLISHMENT_OF_SPINDLE_ORIENTATION, MORF_DNMT1, GOBP_ATTACHMENT_OF_SPINDLE_MICROTUBULES_TO_KINETOCHORE, GOBP_PROTEIN_LOCALIZATION_TO_CYTOSKELETON, HORIUCHI_WTAP_TARGETS_DN, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, SEMBA_FHIT_TARGETS_DN, MORF_BUB1, CROONQUIST_NRAS_SIGNALING_DN, GOBP_SPINDLE_LOCALIZATION, GOBP_CHROMOSOME_LOCALIZATION, MORF_RRM1, DARWICHE_SKIN_TUMOR_PROMOTER_DN

GO Biological Process (10): mitotic sister chromatid segregation (GO:0000070), spindle organization (GO:0007051), chromosome segregation (GO:0007059), positive regulation of intracellular transport (GO:0032388), establishment of spindle orientation (GO:0051294), cell division (GO:0051301), regulation of attachment of spindle microtubules to kinetochore (GO:0051988), protein localization to centrosome (GO:0071539), regulation of metaphase plate congression (GO:0090235), positive regulation of spindle assembly (GO:1905832)

GO Molecular Function (2): microtubule binding (GO:0008017), protein binding (GO:0005515)

GO Cellular Component (18): kinetochore (GO:0000776), cytoplasm (GO:0005737), cytosol (GO:0005829), nuclear body (GO:0016604), midbody (GO:0030496), centriolar satellite (GO:0034451), ciliary rootlet (GO:0035253), microtubule plus-end (GO:0035371), ciliary basal body (GO:0036064), mitotic spindle (GO:0072686), mitotic spindle pole (GO:0097431), chromosome, centromeric region (GO:0000775), spindle pole (GO:0000922), chromosome (GO:0005694), centrosome (GO:0005813), spindle (GO:0005819), cytoskeleton (GO:0005856), microtubule (GO:0005874)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
intracellular membraneless organelle	5
cell cycle process	2
cilium	2
microtubule organizing center	2
spindle	2
microtubule cytoskeleton	2
sister chromatid segregation	1
mitotic nuclear division	1
mitotic cell cycle process	1
microtubule cytoskeleton organization	1
regulation of intracellular transport	1
intracellular transport	1
positive regulation of cellular process	1
positive regulation of transport	1
establishment of cell polarity	1
establishment of spindle localization	1
cellular process	1
attachment of spindle microtubules to kinetochore	1
regulation of cell cycle process	1
protein localization to microtubule organizing center	1
regulation of localization	1
metaphase chromosome alignment	1
spindle assembly	1
positive regulation of cytoskeleton organization	1
positive regulation of cell cycle process	1
regulation of spindle assembly	1
positive regulation of organelle assembly	1
tubulin binding	1
binding	1
condensed chromosome, centromeric region	1
supramolecular complex	1
intracellular anatomical structure	1
cytoplasm	1
nucleoplasm	1
centrosome	1
cytoskeleton	1
microtubule end	1
spindle pole	1
mitotic spindle	1

Protein interactions and networks

STRING

3183 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPAG5	KNSTRN	Q9Y448	934
SPAG5	RPTOR	Q8N122	764
SPAG5	CLASP1	Q7Z460	740
SPAG5	SPAG4	Q9NPE6	737
SPAG5	ODF1	Q14990	712
SPAG5	DYNLL1	P63167	708
SPAG5	PLK1	P53350	660
SPAG5	TOP2A	P11388	649
SPAG5	ASPM	Q8IZT6	641
SPAG5	KIF11	P52732	614
SPAG5	GSK3B	P49841	586
SPAG5	HJURP	Q8NCD3	574
SPAG5	CLASRP	Q8N2M8	571
SPAG5	CDK1	P06493	566
SPAG5	MAD2L1	Q13257	563

IntAct

344 interactions, top by confidence:

A	B	Type	Score
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
SPAG5	LGALS14	psi-mi:“MI:0915”(physical association)	0.720
CCHCR1	SPAG5	psi-mi:“MI:0915”(physical association)	0.720
SPAG5	CCHCR1	psi-mi:“MI:0915”(physical association)	0.720
LGALS14	SPAG5	psi-mi:“MI:0915”(physical association)	0.720
ORC6	SPAG5	psi-mi:“MI:0915”(physical association)	0.670
SPAG5	ORC6	psi-mi:“MI:0915”(physical association)	0.670
SPAG5	CENPH	psi-mi:“MI:0915”(physical association)	0.670
PCM1	KIAA0753	psi-mi:“MI:0914”(association)	0.650
IFT57	IFT56	psi-mi:“MI:0914”(association)	0.640
FAM234B	ABCD4	psi-mi:“MI:0914”(association)	0.620
OSBPL8	SPAG5	psi-mi:“MI:0915”(physical association)	0.600
SPAG5	OSBPL8	psi-mi:“MI:0403”(colocalization)	0.600
BARD1	SPAG5	psi-mi:“MI:0915”(physical association)	0.560
SPAG5	TSHZ3	psi-mi:“MI:0915”(physical association)	0.560
ZFC3H1	SPAG5	psi-mi:“MI:0915”(physical association)	0.560
KANSL1	SPAG5	psi-mi:“MI:0915”(physical association)	0.560
DCX	SPAG5	psi-mi:“MI:0915”(physical association)	0.560
SPAG5	EIF4E2	psi-mi:“MI:0915”(physical association)	0.560
SPAG5	POLR2L	psi-mi:“MI:0915”(physical association)	0.560
SPAG5	GOLGA8F	psi-mi:“MI:0915”(physical association)	0.560
GOLGA8DP	SPAG5	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (260): SPAG5 (Two-hybrid), SPAG5 (Two-hybrid), SPAG5 (Two-hybrid), SPAG5 (Two-hybrid), SPAG5 (Two-hybrid), FBXO28 (Two-hybrid), ORC6 (Two-hybrid), AMOTL2 (Two-hybrid), CCHCR1 (Two-hybrid), CHCHD3 (Two-hybrid), C1orf109 (Two-hybrid), RBM41 (Two-hybrid), LGALS14 (Two-hybrid), TSHZ3 (Two-hybrid), SH2D4A (Two-hybrid)

ESM2 similar proteins: A2AM05, A6NC78, A6NCC3, A6NDK9, A6NDN3, A6NJZ7, A6NMD2, A6NN73, A6NNM3, A7E2F4, A8MQT2, D6RF30, F8WBI6, H3BPF8, H3BQL2, H3BSY2, H3BV12, I6L899, P0CG33, P0CJ92, P0DO97, P0DX52, P0DX53, P54257, Q0D2H9, Q0KK56, Q2M243, Q3T1I3, Q3TCJ8, Q3V0F0, Q5BK57, Q5XHZ2, Q6AW69, Q6AXN6, Q6PHN1, Q7TME2, Q8BG89, Q8BGY3, Q8C0G2, Q8K389

Diamond homologs: Q7TME2, Q96R06

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
GSK3B	up-regulates	SPAG5	phosphorylation
SPAG5	“up-regulates activity”	CENPE
SPAG5	“up-regulates activity”	CENPF
SPAG5	“up-regulates activity”	CDK5RAP2	relocalization
AURKA	“up-regulates activity”	SPAG5	phosphorylation
CDC14A	“down-regulates activity”	SPAG5	dephosphorylation
MID2	“down-regulates quantity by destabilization”	SPAG5	ubiquitination
PLK1	“up-regulates activity”	SPAG5	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 135 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
AURKA Activation by TPX2	13	24.1×	2e-12
Loss of Nlp from mitotic centrosomes	12	23.2×	1e-11
Loss of proteins required for interphase microtubule organization from the centrosome	12	23.2×	1e-11
Regulation of PLK1 Activity at G2/M Transition	13	20.1×	1e-11
Recruitment of mitotic centrosome proteins and complexes	12	19.9×	5e-11
Recruitment of NuMA to mitotic centrosomes	13	18.5×	2e-11
Anchoring of the basal body to the plasma membrane	13	17.9×	2e-11
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	8	11.4×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
centriole replication	7	45.4×	1e-07
protein localization to centrosome	5	29.8×	2e-04
non-motile cilium assembly	7	18.0×	5e-05
centrosome cycle	5	14.9×	2e-03
mitotic spindle organization	6	14.4×	6e-04
positive regulation of transcription elongation by RNA polymerase II	5	13.3×	3e-03
cilium assembly	10	6.5×	6e-04
cell division	12	4.9×	8e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

182 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	139
Likely benign	24
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3461 predictions. Top by Δscore:

Variant	Effect	Δscore
17:28578216:A:AC	donor_gain	1.0000
17:28578217:C:CC	donor_gain	1.0000
17:28578217:CATGG:C	donor_gain	1.0000
17:28578374:T:TA	donor_gain	1.0000
17:28578609:A:AC	donor_gain	1.0000
17:28578610:C:CC	donor_gain	1.0000
17:28578670:A:AC	donor_gain	1.0000
17:28578671:C:CC	donor_gain	1.0000
17:28579248:CACAA:C	acceptor_gain	1.0000
17:28579250:CAA:C	acceptor_gain	1.0000
17:28579253:C:CC	acceptor_gain	1.0000
17:28579361:TCACA:T	donor_loss	1.0000
17:28579362:CA:C	donor_loss	1.0000
17:28579363:A:AC	donor_gain	1.0000
17:28579363:A:T	donor_loss	1.0000
17:28579364:C:CC	donor_gain	1.0000
17:28579364:CA:C	donor_gain	1.0000
17:28579364:CAT:C	donor_gain	1.0000
17:28579364:CATT:C	donor_gain	1.0000
17:28579483:TCTC:T	acceptor_loss	1.0000
17:28579484:CT:C	acceptor_gain	1.0000
17:28579485:TCTG:T	acceptor_loss	1.0000
17:28579486:C:CC	acceptor_gain	1.0000
17:28579487:T:G	acceptor_loss	1.0000
17:28580037:T:TA	donor_gain	1.0000
17:28580038:C:A	donor_gain	1.0000
17:28583507:CTACC:C	donor_loss	1.0000
17:28583509:A:C	donor_loss	1.0000
17:28583510:C:A	donor_loss	1.0000
17:28583510:CCTT:C	donor_gain	1.0000

AlphaMissense

7824 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:28578282:A:G	L1122P	0.993
17:28578503:A:G	L1075P	0.992
17:28578483:C:G	A1082P	0.991
17:28578068:A:G	L1151P	0.987
17:28583984:A:C	F805L	0.987
17:28583984:A:T	F805L	0.987
17:28583986:A:G	F805L	0.987
17:28578383:A:G	L1115P	0.983
17:28578491:A:G	L1079P	0.982
17:28578739:A:G	L1044P	0.982
17:28578524:A:G	L1068P	0.978
17:28579788:G:C	F949L	0.975
17:28579788:G:T	F949L	0.975
17:28579790:A:G	F949L	0.975
17:28578060:A:G	S1154P	0.974
17:28584166:A:G	L799P	0.974
17:28577766:A:G	L1172P	0.973
17:28578461:A:G	L1089P	0.971
17:28578038:A:G	L1161P	0.969
17:28583898:C:G	R834P	0.969
17:28578718:T:G	Q1051P	0.966
17:28583949:A:G	L817P	0.963
17:28578495:A:G	S1078P	0.962
17:28583877:A:G	L841P	0.962
17:28583907:A:G	L831P	0.962
17:28585610:C:G	R595P	0.962
17:28577727:A:G	L1185P	0.961
17:28578488:C:G	R1080P	0.960
17:28591822:A:G	L438P	0.959
17:28578080:A:G	L1147P	0.958

dbSNP variants (sampled 300 via entrez): RS1000006500 (17:28597416 T>A), RS1000182859 (17:28587007 G>A), RS1000204971 (17:28597192 G>A), RS1000519733 (17:28595292 T>A,C), RS1000531152 (17:28595577 G>A), RS1000639669 (17:28587990 G>A,C), RS1000709293 (17:28589699 C>T), RS1000795098 (17:28580646 C>A), RS1001032274 (17:28583935 A>C,G), RS1001137020 (17:28588221 G>A), RS1001239418 (17:28584852 G>A), RS1001293858 (17:28577162 T>TA), RS1001335601 (17:28591673 C>A), RS1001513537 (17:28590468 G>A), RS1001605505 (17:28584443 G>A)

Disease associations

OMIM: gene MIM:615562 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067370 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.74	Kd	1.826	nM	CHEMBL5653589
8.74	ED50	1.826	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149469: Binding affinity to human SPAG5 incubated for 45 mins by Kinobead based pull down assay	kd	0.0018	uM

CTD chemical–gene interactions

92 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, affects expression, decreases expression, increases abundance	5
bisphenol A	affects expression, decreases expression	4
Valproic Acid	affects expression, decreases expression, decreases methylation	4
Cyclosporine	decreases expression	3
trichostatin A	affects cotreatment, decreases expression	2
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	2
(+)-JQ1 compound	decreases expression	2
Resveratrol	increases expression, affects cotreatment	2
Acetaminophen	decreases expression, increases expression	2
Hydrogen Peroxide	affects expression	2
Nickel	increases expression	2
Rotenone	decreases expression, increases expression	2
Aflatoxin B1	affects expression, increases methylation	2
Vitamin K 3	affects expression	2
FR900359	increases phosphorylation	1
2,4,6-tribromophenol	decreases expression	1
propionaldehyde	decreases expression	1
deoxynivalenol	increases expression	1
glycidyl methacrylate	decreases expression	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
tetrabromobisphenol A	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
manganese chloride	decreases expression, increases abundance	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
coumarin	increases phosphorylation	1
diallyl trisulfide	decreases expression	1
2,3-dimethoxy-1,4-naphthoquinone	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652511	Binding	Binding affinity to human SPAG5 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3HY	Abcam HEK293T SPAG5 KO	Transformed cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.