SKA2

Summary

SKA2 (spindle and kinetochore associated complex subunit 2, HGNC:28006) is a protein-coding gene on chromosome 17q23.2, encoding Spindle and kinetochore-associated protein 2 (Q8WVK7). Component of the SKA1 complex, a microtubule-binding subcomplex of the outer kinetochore that is essential for proper chromosome segregation. It is a selective cancer dependency (DepMap: 74.5% of cell lines).

Enables microtubule binding activity. Involved in attachment of mitotic spindle microtubules to kinetochore and regulation of microtubule polymerization or depolymerization. Located in kinetochore and spindle microtubule. Part of SKA complex.

Source: NCBI Gene 348235 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 25 total
• Cancer dependency (DepMap): dependent in 74.5% of screened cell lines
• MANE Select transcript: NM_182620

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28006
Approved symbol	SKA2
Name	spindle and kinetochore associated complex subunit 2
Location	17q23.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ12758
Ensembl gene	ENSG00000182628
Ensembl biotype	protein_coding
OMIM	616674
Entrez	348235

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000330137, ENST00000437036, ENST00000578105, ENST00000578519, ENST00000580541, ENST00000581068, ENST00000583380, ENST00000583927, ENST00000583976, ENST00000584089, ENST00000916133

RefSeq mRNA: 3 — MANE Select: NM_182620 NM_001100595, NM_001330399, NM_182620

CCDS: CCDS45747, CCDS45748, CCDS82175

Canonical transcript exons

ENST00000330137 — 4 exons

Exon	Start	End
ENSE00001324111	59155131	59155186
ENSE00002734637	59109857	59112345
ENSE00003478713	59119319	59119495
ENSE00003636954	59131281	59131367

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 98.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 54.1182 / max 3944.4436, expressed in 1795 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
167325	51.4165	1792
167326	2.6384	1121
167323	0.0634	31

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	98.83	gold quality
ganglionic eminence	UBERON:0004023	98.75	gold quality
endothelial cell	CL:0000115	97.79	gold quality
cortical plate	UBERON:0005343	97.58	gold quality
cerebellar vermis	UBERON:0004720	96.77	gold quality
oviduct epithelium	UBERON:0004804	96.32	gold quality
corpus callosum	UBERON:0002336	95.07	gold quality
calcaneal tendon	UBERON:0003701	95.05	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.65	gold quality
spinal cord	UBERON:0002240	94.63	gold quality
cerebellum	UBERON:0002037	94.27	gold quality
cerebellar cortex	UBERON:0002129	94.15	gold quality
cerebellar hemisphere	UBERON:0002245	94.05	gold quality
medulla oblongata	UBERON:0001896	94.04	gold quality
pons	UBERON:0000988	93.95	gold quality
ventral tegmental area	UBERON:0002691	93.69	gold quality
subthalamic nucleus	UBERON:0001906	93.67	gold quality
inferior vagus X ganglion	UBERON:0005363	93.57	gold quality
hypothalamus	UBERON:0001898	93.48	gold quality
esophagus squamous epithelium	UBERON:0006920	93.48	gold quality
superior vestibular nucleus	UBERON:0007227	93.47	gold quality
amygdala	UBERON:0001876	93.43	gold quality
ileal mucosa	UBERON:0000331	93.28	gold quality
substantia nigra	UBERON:0002038	93.23	gold quality
midbrain	UBERON:0001891	93.17	gold quality
medial globus pallidus	UBERON:0002477	93.16	gold quality
dorsal plus ventral thalamus	UBERON:0001897	92.80	gold quality
secondary oocyte	CL:0000655	92.66	gold quality
globus pallidus	UBERON:0001875	92.63	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.63	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-10	yes	34.93
E-CURD-122	yes	22.49
E-HCAD-1	yes	17.50
E-MTAB-4850	no	206.15
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4

miRNA regulators (miRDB)

74 targeting SKA2, 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-7110-3P	100.00	73.18	2486
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-3913-3P	99.74	66.53	938
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-3177-5P	99.65	70.38	1174
HSA-MIR-6516-3P	99.65	68.57	1238
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-378A-5P	99.65	66.33	1311
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-12123	99.52	71.79	2990

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 74.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 32)

• These data suggest that the Ska1/Ska2 complex plays a critical role in the maintenance of the metaphase plate and/or spindle checkpoint silencing. (PMID:17093495)
• Study discovered that FAM33A is protein partners for GRs and is involved in cell proliferation and GC signalling. (PMID:18583474)
• blocking of miR-301 in A549 cells leads to a decrease in the expression of the host gene, ska2. (PMID:20470754)
• Data suggest that Aurora B phosphorylation antagonizes the interaction between the Ska1-3 complex and the KMN network, thereby controlling Ska recruitment to KTs and stabilization of KT-MT attachments. (PMID:22371557)
• The structure of the Ska core complex is a W-shaped dimer of coiled coils, formed by intertwined interactions between Ska1, Ska2, and Ska3. (PMID:22483620)
• SKA2 significantly interacted with anxiety and stress to explain about 80% of suicidal behavior and progression from suicidal ideation to suicide attempt.SKA2 is a novel genetic and epigenetic marker involved in the etiology of suicide, suicidal behaviors (PMID:25073599)
• PRR11-SKA2 bidirectional transcription unit, which is a novel direct target of NF-Y, is essential for the accelerated proliferation and motility of lung cancer cells (PMID:26162986)
• SKA2 is hypothesized to reduce the ability to suppress cortisol following stress. (PMID:26305478)
• Results suggest that DNA methylation(adj) of SKA2 in blood indexes stress-related psychiatric phenotypes and neurobiology, pointing to its potential value as a biomarker of stress exposure and susceptibility. (PMID:26324104)
• these data establish the importance of SKA2 for cortisol stress responsivity and the development of post-traumatic stress disorder and provide further evidence that SKA2 is a promising biomarker for stress-related disorders including PTSD. (PMID:26361058)
• The study adds evidence that CREB, a tumor oncogene, promotes renal cell carcinoma proliferation. It probably achieves this by increasing SKA2 expression (PMID:26824422)
• study shows that decreased gene and protein expression of SKA2 observed in the prefrontal cortex of suicide victims is specific to suicide, which was not observed in the brain of nonsuicidal patients. It also indicates reduced SKA2 expression in suicide is independent of psychiatric diagnosis, since it is observed in all diagnostic groups studied. (PMID:26902949)
• Possible association between SKA2 expression in prefrontal cortex and MDD. (PMID:27030168)
• DNA methylation of the SKA2 gene has been implicated as a biomarker of suicide risk and posttraumatic stress disorder. (PMID:27038412)
• Data show that HOTAIR might act as an endogenous ‘sponge’ of miR-141, thereby regulating the derepression of SKA2. (PMID:27121316)
• p53 negatively regulates the expression of the PRR11-SKA2 bidirectional transcription unit through NF-Y, suggesting that the inability to repress the PRR11-SKA2 bidirectional transcription unit after loss of p53 might contribute to tumorigenesis. (PMID:28257042)
• Kinetochores mature through Ska1/ska2/Ska3 complex recruitment and this is required for improved load-bearing capacity and silencing of the spindle assembly checkpoint. (PMID:28495837)
• decreased neuronal cell SKA complex genes’ expression levels affect neuronal cell viability and neurite development (PMID:29268205)
• We aimed to explore the biological activity of lncRNA SPRY4-IT1 in breast cancer cells and whether N-terminal polypeptide derived from viral macrophage inflammatory protein II (NT21MP) could exert its anti-tumor effect by regulating lncRNA SPRY4-IT1 and its target gene SKA2 (PMID:30104400)
• SKA2 may be associated with breast cancer metastasis. (PMID:30387823)
• Breast cancer patients with lower expression levels of either PRR11 or SKA2, along with wild type p53, exhibited better disease-free survival compared to others with p53 mutations and/or higher expression levels of either PRR11 or SKA2. Study indicates that the PRR11 and SKA2 transcription unit might be an oncogenic contributor. (PMID:30760381)
• The results of the current study suggest that prognosis of women with the AA genotype are more susceptible to be spontaneous preterm birth. (PMID:31035118)
• SKA2 promotes proliferation and invasion of hepatocellular carcinoma cells via activating the beta-catenin signaling pathway. (PMID:32241158)
• The Shift of HbF to HbA under Influence of SKA2 Gene; A Possible Link between Cortisol and Hematopoietic Maturation in Term and Preterm Newborns. (PMID:32364083)
• Spindle and kinetochore-associated protein 2 facilitates the proliferation and invasion of hepatocellular carcinoma via the regulation of Wnt/beta-catenin signaling. (PMID:32682011)
• Circ_0008039 supports breast cancer cell proliferation, migration, invasion, and glycolysis by regulating the miR-140-3p/SKA2 axis. (PMID:33244865)
• HEDGEHOG/GLI Modulates the PRR11-SKA2 Bidirectional Transcription Unit in Lung Squamous Cell Carcinomas. (PMID:33477943)
• Resting mononuclear cell NR3C1 and SKA2 expression levels predict blunted cortisol reactivity to combat training stress among elite army cadets exposed to childhood adversity. (PMID:33981010)
• Transcript levels of spindle and kinetochore-associated complex 1/3 as prognostic biomarkers correlated with immune infiltrates in hepatocellular carcinoma. (PMID:34045512)
• The rs7208505 Polymorphism and Differential Expression of the SKA2 Gene in the Prefrontal Cortex of Suicide Victims from the Mexican Population. (PMID:37204142)
• Decreased mononuclear cell NR3C1 SKA2 and FKPB5 expression levels among adult survivors of suicide bombing terror attacks in childhood are associated with the development of PTSD. (PMID:37845495)
• SKA2 regulated hyperactive secretory autophagy drives neuroinflammation-induced neurodegeneration. (PMID:38528004)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ska2	ENSDARG00000114038
mus_musculus	Ska2	ENSMUSG00000020492
rattus_norvegicus	Ska2l1	ENSRNOG00000020446
rattus_norvegicus	Ska2	ENSRNOG00000025981

Protein

Protein identifiers

Spindle and kinetochore-associated protein 2 — Q8WVK7 (reviewed: Q8WVK7)

Alternative names: Protein FAM33A

All UniProt accessions (8): Q8WVK7, J3KRW9, J3KRZ0, J3KSP0, J3KTC5, J3QKN8, J3QL03, J3QS74

UniProt curated annotations — full annotation on UniProt →

Function. Component of the SKA1 complex, a microtubule-binding subcomplex of the outer kinetochore that is essential for proper chromosome segregation. Required for timely anaphase onset during mitosis, when chromosomes undergo bipolar attachment on spindle microtubules leading to silencing of the spindle checkpoint. The SKA1 complex is a direct component of the kinetochore-microtubule interface and directly associates with microtubules as oligomeric assemblies. The complex facilitates the processive movement of microspheres along a microtubule in a depolymerization-coupled manner. In the complex, it is required for SKA1 localization. Affinity for microtubules is synergistically enhanced in the presence of the ndc-80 complex and may allow the ndc-80 complex to track depolymerizing microtubules.

Subunit / interactions. Component of the SKA1 complex, composed of SKA1, SKA2 and SKA3. Forms a heterodimer with SKA1; the heterodimer interacting with SKA3. The core SKA1 complex is composed of 2 SKA1-SKA2 heterodimers, each heterodimer interacting with a molecule of the SKA3 homodimer. The core SKA1 complex associates with microtubules and forms oligomeric assemblies. Interacts directly with SKA1. Binds directly to microtubules; but with a much lower affinity than SKA1. May interact with NR3C1; the relevance of such interaction remains unclear in vivo.

Subcellular location. Cytoplasm. Cytoskeleton. Spindle. Chromosome. Centromere. Kinetochore.

Similarity. Belongs to the SKA2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8WVK7-1	1	yes
Q8WVK7-2	2

RefSeq proteins (3): NP_001094065, NP_001317328, NP_872426* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026762	Ska2	Family
IPR042091	Ska2_N	Domain

Pfam: PF16740

UniProt features (7 total): helix 3, splice variant 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4AJ5	X-RAY DIFFRACTION	3.32

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WVK7-F1	88.53	0.52

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 (1): 101

Function

Pathways and Gene Ontology

Reactome pathways

18 pathways

ID	Pathway
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-68877	Mitotic Prometaphase
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation
R-HSA-141424	Amplification of signal from the kinetochores
R-HSA-162582	Signal Transduction
R-HSA-1640170	Cell Cycle
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-2555396	Mitotic Metaphase and Anaphase
R-HSA-68882	Mitotic Anaphase
R-HSA-68886	M Phase
R-HSA-69278	Cell Cycle, Mitotic
R-HSA-69618	Mitotic Spindle Checkpoint
R-HSA-69620	Cell Cycle Checkpoints
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 247 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, GOBP_CHROMOSOME_ORGANIZATION, GOBP_ESTABLISHMENT_OF_SPINDLE_ORIENTATION, GOBP_ATTACHMENT_OF_SPINDLE_MICROTUBULES_TO_KINETOCHORE, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_SPINDLE_LOCALIZATION, GOBP_CHROMOSOME_LOCALIZATION, WANG_RECURRENT_LIVER_CANCER_UP, CAGCTG_AP4_Q5, GOBP_ESTABLISHMENT_OF_CELL_POLARITY

GO Biological Process (9): mitotic sister chromatid segregation (GO:0000070), mitotic cell cycle (GO:0000278), spindle assembly involved in female meiosis (GO:0007056), chromosome segregation (GO:0007059), mitotic metaphase chromosome alignment (GO:0007080), regulation of microtubule polymerization or depolymerization (GO:0031110), establishment of meiotic spindle orientation (GO:0051296), cell division (GO:0051301), attachment of mitotic spindle microtubules to kinetochore (GO:0051315)

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

GO Cellular Component (12): kinetochore (GO:0000776), outer kinetochore (GO:0000940), cytosol (GO:0005829), spindle microtubule (GO:0005876), meiotic spindle (GO:0072687), SKA complex (GO:0170027), chromosome, centromeric region (GO:0000775), chromosome (GO:0005694), cytoplasm (GO:0005737), spindle (GO:0005819), cytoskeleton (GO:0005856), microtubule (GO:0005874)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Mitotic Prometaphase	2
M Phase	2
Cell Cycle	2
Amplification of signal from the kinetochores	1
Mitotic Anaphase	1
RHO GTPase Effectors	1
Mitotic Spindle Checkpoint	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Mitotic Metaphase and Anaphase	1
Cell Cycle, Mitotic	1
Cell Cycle Checkpoints	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membraneless organelle	4
mitotic cell cycle process	3
mitotic nuclear division	2
protein-containing complex	2
cellular anatomical structure	2
spindle	2
microtubule cytoskeleton	2
sister chromatid segregation	1
cell cycle	1
female meiotic nuclear division	1
meiotic spindle assembly	1
cell cycle process	1
mitotic sister chromatid segregation	1
mitotic cell cycle	1
metaphase chromosome alignment	1
microtubule polymerization or depolymerization	1
regulation of microtubule cytoskeleton organization	1
establishment of spindle orientation	1
establishment of meiotic spindle localization	1
meiotic cell cycle	1
cellular process	1
mitotic metaphase chromosome alignment	1
attachment of spindle microtubules to kinetochore	1
tubulin binding	1
binding	1
condensed chromosome, centromeric region	1
supramolecular complex	1
kinetochore	1
cytoplasm	1
microtubule	1
outer kinetochore	1
chromosomal region	1
intracellular anatomical structure	1
polymeric cytoskeletal fiber	1

Protein interactions and networks

STRING

718 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SKA2	SKA1	Q96BD8	996
SKA2	SKA3	Q8IX90	996
SKA2	NR3C1	P04150	615
SKA2	FKBP5	Q13451	605
SKA2	BUB1	O43683	593
SKA2	PRR11	Q96HE9	580
SKA2	KNL1	Q8NG31	571
SKA2	SGO1	Q5FBB7	555
SKA2	NDC80	O14777	551
SKA2	SPC24	Q8NBT2	548
SKA2	CENPS	Q8N2Z9	541
SKA2	ERCC6L	Q2NKX8	518
SKA2	CENPI	Q92674	514
SKA2	NUF2	Q9BZD4	502
SKA2	PPP2R2B	Q00005	485

IntAct

58 interactions, top by confidence:

A	B	Type	Score
SKA1	SKA3	psi-mi:“MI:0915”(physical association)	0.930
SKA2	SKA1	psi-mi:“MI:0403”(colocalization)	0.880
SKA1	SKA2	psi-mi:“MI:0915”(physical association)	0.880
SKA2	SKA1	psi-mi:“MI:0915”(physical association)	0.880
SKA2	SKA3	psi-mi:“MI:0914”(association)	0.830
SKA3	SKA2	psi-mi:“MI:0914”(association)	0.830
PPP2R2B	MYO9A	psi-mi:“MI:0914”(association)	0.640
PPP2R2C	TCP1	psi-mi:“MI:0914”(association)	0.640
SKA3	NOL4	psi-mi:“MI:0914”(association)	0.640
RALY	SKA2	psi-mi:“MI:0915”(physical association)	0.560
SKA2	IFT57	psi-mi:“MI:0915”(physical association)	0.560
SKA3	CCDC85C	psi-mi:“MI:0914”(association)	0.530
HAUS1	BET1	psi-mi:“MI:0914”(association)	0.530
RALYL	CDC40	psi-mi:“MI:0914”(association)	0.530
SKA2	VSIG8	psi-mi:“MI:0914”(association)	0.530
KIAA0753	OFD1	psi-mi:“MI:2364”(proximity)	0.480
HSPA8	ARHGEF10	psi-mi:“MI:2364”(proximity)	0.480
PPP2R2B	DDX3X	psi-mi:“MI:0914”(association)	0.460

BioGRID (53): SKA2 (Affinity Capture-MS), SKA2 (Proximity Label-MS), SKA2 (Proximity Label-MS), SKA2 (Proximity Label-MS), SKA2 (Affinity Capture-MS), SKA2 (Affinity Capture-MS), SKA2 (Affinity Capture-MS), SKA2 (Affinity Capture-MS), SKA2 (Affinity Capture-MS), SKA2 (Affinity Capture-MS), SKA2 (Proximity Label-MS), SKA2 (Proximity Label-MS), SKA2 (Two-hybrid), SKA2 (Two-hybrid), SKA2 (Positive Genetic)

ESM2 similar proteins: A0A0H2XIK2, A0RH02, A8FB03, B7I056, B7JI37, B9DMV6, B9IUC0, C1EN48, C3L9C5, C3P449, C5D5A9, O31893, O32265, O66410, O84672, P04537, P07533, P0C051, P13848, P15234, P25186, P39101, P52475, P64665, P64666, P68583, P68584, Q01050, Q04EL5, Q2L7C5, Q4R8E8, Q54ID4, Q57915, Q5HJ85, Q637L7, Q65MG3, Q6GCI4, Q6HFI9, Q6NWL1, Q6NX65

Diamond homologs: B5X5N3, Q0P426, Q2TBY0, Q4R8E8, Q5I0J4, Q8WVK7, Q9CR46

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SKA2	“form complex”	“SKA complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 52 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
RHOA GTPase cycle	5	14.3×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
cell division	7	7.7×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	13
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

725 predictions. Top by Δscore:

Variant	Effect	Δscore
17:59112343:CAG:C	acceptor_gain	1.0000
17:59112344:AG:A	acceptor_gain	0.9900
17:59112346:C:CC	acceptor_gain	0.9900
17:59119313:CATTA:C	donor_loss	0.9900
17:59119314:ATT:A	donor_loss	0.9900
17:59119315:TTACC:T	donor_loss	0.9900
17:59119316:TACC:T	donor_loss	0.9900
17:59119318:C:CT	donor_loss	0.9900
17:59119320:T:TA	donor_gain	0.9900
17:59119491:TTTTT:T	acceptor_gain	0.9900
17:59119492:TTTT:T	acceptor_gain	0.9900
17:59119496:C:CC	acceptor_gain	0.9900
17:59119498:A:AC	acceptor_gain	0.9900
17:59119498:A:C	acceptor_gain	0.9900
17:59119502:C:CT	acceptor_gain	0.9900
17:59119503:A:T	acceptor_gain	0.9900
17:59120636:A:C	donor_gain	0.9900
17:59131280:CCTCA:C	donor_gain	0.9900
17:59131285:CTTG:C	donor_gain	0.9900
17:59131368:C:CC	acceptor_gain	0.9900
17:59112216:T:TA	donor_gain	0.9800
17:59112347:T:C	acceptor_loss	0.9800
17:59119493:TTT:T	acceptor_gain	0.9800
17:59119494:TT:T	acceptor_gain	0.9800
17:59119494:TTCT:T	acceptor_loss	0.9800
17:59119495:TC:T	acceptor_loss	0.9800
17:59119496:C:CA	acceptor_loss	0.9800
17:59119497:T:G	acceptor_loss	0.9800
17:59131275:GATTA:G	donor_loss	0.9800
17:59131277:TTACC:T	donor_loss	0.9800

AlphaMissense

795 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:59131365:G:C	F12L	0.945
17:59131365:G:T	F12L	0.945
17:59131367:A:G	F12L	0.945
17:59131358:C:G	A15P	0.923
17:59131359:T:A	K14N	0.922
17:59131359:T:G	K14N	0.922
17:59131360:T:A	K14I	0.916
17:59131366:A:G	F12S	0.892
17:59131352:A:G	S17P	0.870
17:59131324:A:G	L26P	0.865
17:59155131:C:A	M11I	0.851
17:59155131:C:G	M11I	0.851
17:59155131:C:T	M11I	0.851
17:59131357:G:T	A15D	0.846
17:59155135:A:G	L10P	0.831
17:59131360:T:G	K14T	0.829
17:59131347:A:C	D18E	0.828
17:59131347:A:T	D18E	0.828
17:59131345:A:G	L19P	0.820
17:59131348:T:C	D18G	0.809
17:59131349:C:G	D18H	0.797
17:59119341:A:G	L92P	0.793
17:59155141:A:G	L8P	0.790
17:59119454:C:A	K54N	0.789
17:59119454:C:G	K54N	0.789
17:59131361:T:C	K14E	0.788
17:59131361:T:G	K14Q	0.776
17:59131348:T:G	D18A	0.772
17:59131336:A:G	I22T	0.765
17:59131348:T:A	D18V	0.760

dbSNP variants (sampled 300 via entrez): RS1000014474 (17:59123900 A>G), RS1000042368 (17:59115073 A>G,T), RS1000058127 (17:59132317 T>C), RS1000108990 (17:59113389 G>T), RS1000114973 (17:59120878 C>T), RS1000214780 (17:59112205 AC>A), RS1000307472 (17:59125716 A>G,T), RS1000459979 (17:59113584 G>T), RS1000649543 (17:59113439 C>T), RS1000654712 (17:59141119 C>T), RS1000715110 (17:59147722 C>G,T), RS1000753625 (17:59120001 C>T), RS1000888218 (17:59139319 C>G,T), RS1000943293 (17:59141329 G>A), RS1001005189 (17:59145272 G>A)

Disease associations

OMIM: gene MIM:616674 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002023_1	Testicular germ cell tumor	4.000000e-13
GCST002774_29	Cognitive function	3.000000e-07
GCST010002_126	Refractive error	7.000000e-42

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	3
Cyclosporine	decreases expression	3
Particulate Matter	decreases expression, increases abundance	3
Resveratrol	affects cotreatment, increases expression	2
Air Pollutants	decreases expression, increases abundance	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Cisplatin	affects cotreatment, decreases expression, increases expression	2
Methotrexate	decreases expression	2
Valproic Acid	decreases methylation, decreases expression	2
GSK-J4	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
arsenite	affects binding, increases reaction	1
methylparaben	decreases expression	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	increases expression, affects cotreatment	1
phenethyl isothiocyanate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
NSC 689534	affects binding, decreases expression	1
Sunitinib	decreases expression	1

Clinical trials (associated diseases)

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