SKA1

Summary

SKA1 (spindle and kinetochore associated complex subunit 1, HGNC:28109) is a protein-coding gene on chromosome 18q21.1, encoding SKA complex subunit 1 (Q96BD8). Component of the SKA complex, a microtubule plus end-binding complex of the outer kinetochore that stabilizes spindle microtubule-kinetochore attachments, promotes alignment of chromosomes at the mitotic spindle equator (chromosome congression) and assists suppression of the spi…. It is a selective cancer dependency (DepMap: 53.6% of cell lines).

Enables microtubule binding activity. Involved in attachment of mitotic spindle microtubules to kinetochore; negative regulation of mitotic spindle assembly checkpoint signaling; and positive regulation of microtubule polymerization. Located in several cellular components, including intercellular bridge; kinetochore; and microtubule cytoskeleton. Part of SKA complex.

Source: NCBI Gene 220134 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 31 total
• Cancer dependency (DepMap): dependent in 53.6% of screened cell lines
• MANE Select transcript: NM_145060

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28109
Approved symbol	SKA1
Name	spindle and kinetochore associated complex subunit 1
Location	18q21.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC10200
Ensembl gene	ENSG00000154839
Ensembl biotype	protein_coding
OMIM	616673
Entrez	220134

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000285116, ENST00000398452, ENST00000417656, ENST00000488454, ENST00000494518, ENST00000919864, ENST00000919865, ENST00000919866

RefSeq mRNA: 2 — MANE Select: NM_145060 NM_001039535, NM_145060

CCDS: CCDS11946

Canonical transcript exons

ENST00000285116 — 7 exons

Exon	Start	End
ENSE00001103323	50380126	50380250
ENSE00001880889	50375046	50375194
ENSE00001956031	50392099	50394168
ENSE00003495472	50382129	50382226
ENSE00003544284	50391124	50391293
ENSE00003565567	50385216	50385353
ENSE00003686642	50375820	50375918

Expression profiles

Bgee: expression breadth ubiquitous, 124 present calls, max score 85.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.7645 / max 440.3648, expressed in 1431 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
170251	7.2032	1217
170250	4.9995	1124
170249	3.3552	1036
170252	0.2066	115

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.82	gold quality
ventricular zone	UBERON:0003053	81.79	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.07	gold quality
ganglionic eminence	UBERON:0004023	78.33	gold quality
bone marrow	UBERON:0002371	78.04	gold quality
adrenal tissue	UBERON:0018303	77.55	gold quality
stromal cell of endometrium	CL:0002255	75.78	gold quality
lymph node	UBERON:0000029	73.16	gold quality
mucosa of transverse colon	UBERON:0004991	72.77	gold quality
bone marrow cell	CL:0002092	72.44	gold quality
rectum	UBERON:0001052	71.67	gold quality
vermiform appendix	UBERON:0001154	70.95	gold quality
placenta	UBERON:0001987	70.02	gold quality
endometrium	UBERON:0001295	69.47	gold quality
duodenum	UBERON:0002114	68.18	gold quality
testis	UBERON:0000473	67.79	gold quality
smooth muscle tissue	UBERON:0001135	67.45	gold quality
esophagus mucosa	UBERON:0002469	67.36	gold quality
right testis	UBERON:0004534	66.80	gold quality
lower esophagus mucosa	UBERON:0035834	66.71	gold quality
left testis	UBERON:0004533	65.80	gold quality
tonsil	UBERON:0002372	61.67	gold quality
colonic epithelium	UBERON:0000397	59.26	silver quality
islet of Langerhans	UBERON:0000006	59.23	gold quality
spleen	UBERON:0002106	58.61	gold quality
blood	UBERON:0000178	58.44	gold quality
right adrenal gland cortex	UBERON:0035827	57.23	gold quality
right adrenal gland	UBERON:0001233	57.02	gold quality
granulocyte	CL:0000094	56.12	gold quality
adrenal gland	UBERON:0002369	55.89	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	8.57
E-ANND-3	no	1.26

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

71 targeting SKA1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-6883-5P	99.69	68.05	3785

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 53.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 38)

• 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)
• The full Ska1 complex forms assemblies on microtubules that can facilitate the processive movement of microspheres along depolymerizing microtubules. (PMID:19289083)
• 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)
• the conserved kinetochore-localized Ska1 complex tracks with depolymerizing microtubule ends and associates with both the microtubule lattice and curved protofilaments (PMID:23085020)
• Data suggest that SKA1 plays an important role in the proliferation of hepatocellular carcinoma cells (PMID:24010405)
• the kinetochore-associated Ska complex interacts with tubulin monomers via the carboxy-terminal winged-helix domain of Ska1, providing the structural basis for the ability to bind both straight and curved microtubule structures. (PMID:24413531)
• SKA1 could be used for gastric cancer early diagnosis as a biomarker. (PMID:24627241)
• Ska1 over-expression promotes tumourigenesis (PMID:24827423)
• Results show that high SKA1 expression is predictive of poor prognosis of papillary thyroid carcinoma (PTC), implying it as a promising new target for PTC therapies. (PMID:26063960)
• knockdown of SKA1 could potently suppress bladder cancer cell proliferation in vitro and lentivirus-mediated silencing of SKA1 might serve as a novel strategy for gene therapy of bladder cancer. (PMID:26197237)
• Thus, our findings identified a definite regulatory mechanism of the search and capture process for stable spindle attachment through cross-talk between spindle dynamics and KT composition mediated by DDA3 and Ska1. (PMID:26797278)
• expression positively associated with tumor-node-metastasis stage and recurrence of salivary adenoid cystic carcinoma (PMID:26881872)
• Thus, the Ska complex, specifically the Ska1 C-terminal domain, recruits PP1 to kinetochores to oppose spindle checkpoint signaling kinases and promote anaphase onset. (PMID:26981768)
• SKA1 is required for metastasis and cisplatin resistance of non-small cell lung cancer. (PMID:26985856)
• End-binding protein 1 (EB1) depletion results in a significant reduction of spindle and kinetochore-associated protein 1 (Ska1) recruitment onto microtubules and defects in mitotic chromosome alignment. (PMID:27225956)
• Study indicated that hypoxia mediated downregulation of SKA1 expression increased the chemotherapy resistance in human osteosarcoma cells. (PMID:28278080)
• SKA1 might be a promising target for cancer gene therapy in human ACC. (PMID:28340379)
• 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)
• In conclusion, our findings suggest that spindle and kinetochore-associated protein 1 could serve as a potential therapeutic target in prostate cancer patients. (PMID:28651496)
• Results show that SKA1 expression is regulated by mir-10a. Its knockdown inhibits migration and invasion in renal cell carcinoma cells. (PMID:28746769)
• decreased neuronal cell SKA complex genes’ expression levels affect neuronal cell viability and neurite development (PMID:29268205)
• High SKA1 expression is associated with early recurrence and progression in patients with NMIBC, indicating SKA1 may serve as a promising prognostic biomarker for this disease. (PMID:29865039)
• ZFAS1 promotes growth and metastasis of ccRCC via targeting miR-10a/SKA1 pathway. (PMID:30841471)
• our study has established the de novo MTX-resistant cell line SF-86 and identified SKA1 as a novel regulator of FPGS, playing a key role in the development of de novo MTX-resistance in osteosarcoma (OS). (PMID:30851225)
• SKA1 was significantly overexpressed in ESCC cells. (PMID:31545481)
• This study demonstrated that SKA1 enhanced pancreatic cancer aggressiveness by inhibiting G2/M arrest and regulating actin cytoskeleton organization via activating Cdc42. (PMID:32232899)
• Prognostic value and functional bioinformatic analysis of spindle- and kinetochore-associated protein 1 in stage IIA esophageal squamous cell carcinoma. (PMID:33004764)
• miRNA-10a-5p inhibits cell metastasis in hepatocellular carcinoma via targeting SKA1. (PMID:34002462)
• Transcript levels of spindle and kinetochore-associated complex 1/3 as prognostic biomarkers correlated with immune infiltrates in hepatocellular carcinoma. (PMID:34045512)
• Circular RNA FAT atypical cadherin 1 (circFAT1)/microRNA-525-5p/spindle and kinetochore-associated complex subunit 1 (SKA1) axis regulates oxaliplatin resistance in breast cancer by activating the notch and Wnt signaling pathway. (PMID:34288822)
• ETV5 overexpression promotes progression of esophageal squamous cell carcinoma by upregulating SKA1 and TRPV2. (PMID:35813298)
• SKA1 is overexpressed in laryngocarcinoma and modulates cell growth via P53 signaling pathway. (PMID:36397719)
• SKA1 promotes tumor metastasis via SAFB-mediated transcription repression of DUSP6 in clear cell renal cell carcinoma. (PMID:36462498)
• Kinetochore-microtubule attachment in human cells is regulated by the interaction of a conserved motif of Ska1 with EB1. (PMID:36592928)
• Hypoxia-induced lncRNA MRVI1-AS1 accelerates hepatocellular carcinoma progression by recruiting RNA-binding protein CELF2 to stabilize SKA1 mRNA. (PMID:36973749)
• Integrated analysis of SKA1-related ceRNA network and SKA1 immunoassays in HCC: A study based on bioinformatic. (PMID:37746945)
• Preliminary exploration of SKA1 expression in lung adenocarcinoma and its clinical significance. (PMID:37814813)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ska1	ENSMUSG00000036223
rattus_norvegicus	Ska1	ENSRNOG00000015275

Protein

Protein identifiers

SKA complex subunit 1 — Q96BD8 (reviewed: Q96BD8)

Alternative names: Spindle and kinetochore-associated protein 1

All UniProt accessions (3): Q96BD8, K7EP61, K7EPW0

UniProt curated annotations — full annotation on UniProt →

Function. Component of the SKA complex, a microtubule plus end-binding complex of the outer kinetochore that stabilizes spindle microtubule-kinetochore attachments, promotes alignment of chromosomes at the mitotic spindle equator (chromosome congression) and assists suppression of the spindle assembly checkpoint. Kinetochores, consisting of a centromere-associated inner segment and a microtubule-contacting outer segment, play a crucial role in chromosome segregation by mediating the physical connection between centromeric DNA and spindle microtubules. The outer kinetochore is made up of the ten-subunit KMN network complex, comprising the MIS12, NDC80 and KNL1 complexes, and auxiliary microtubule-associated components such as the SKA complex; together they connect the outer kinetochore with the inner kinetochore, bind microtubules, and mediate interactions with mitotic checkpoint proteins that delay anaphase until chromosomes are bioriented on the spindle. The SKA complex is loaded onto bioriented kinetochores and it facilitates chromosome congression by stabilizing microtubules together with MAPRE1, and end-on attachment of the NDC80 complex to depolymerizing spindle microtubules, thereby assisting the poleward-moving kinetochore in withstanding microtubule pulling forces. The complex associates with dynamic microtubule plus-ends and can track both depolymerizing and elongating microtubules. The complex recruits protein phosphatase 1 (PP1) to the kinetochore in prometaphase and metaphase, to oppose spindle assembly checkpoint signaling and promote the onset of anaphase. In the complex, it mediates interactions with microtubules. It also stimulates AURKB/Aurora B catalytic activity. During meiosis the SKA complex stabilizes the meiotic spindle and is required for its migration to the cortex.

Subunit / interactions. Component of the SKA complex, composed of SKA1, SKA2 and SKA3. The SKA complex is a homodimer organized around a central W-shaped coiled-coil structure, formed by the interacting domains of SKA1, SKA2, and SKA3, each end of the ‘W’ is extended further by the C-terminal microtubule-binding domains of SKA1 and SKA3; the complex forms extended structures on microtubules. Interacts (via SXLP motif) with MAPRE1 (via C-terminus); the interaction is direct and stabilizes the kinetochore-microtubule attachment of the SKA1 complex. Interacts (via C-terminus) with protein phosphatase PP1 subunit PPP1CA; the interaction is direct and required for recruitment of PPP1CA to the kinetochore. Interacts with the NDC80 complex; the interaction is required to establish kinetochore-microtubule end-on attachments.

Subcellular location. Cytoplasm. Cytoskeleton. Spindle. Chromosome. Centromere. Kinetochore. Microtubule organizing center. Centrosome.

Post-translational modifications. Phosphorylated by AURKB at Thr-157 and Ser-242 which negatively regulates the association of the SKA complex with kinetochores to allow correction of aberrant kinetochore-microtubule interactions and promote mitotic sister chromatid biorientation.

Similarity. Belongs to the SKA1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96BD8-1	1	yes
Q96BD8-2	2

RefSeq proteins (2): NP_001034624, NP_659497* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009829	SKA1	Family
IPR042031	SKA1_MBD_sf	Homologous_superfamily

Pfam: PF07160

UniProt features (38 total): mutagenesis site 11, helix 10, modified residue 3, region of interest 3, strand 3, initiator methionine 1, chain 1, splice variant 1, sequence variant 1, turn 1, coiled-coil region 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4C9Y	X-RAY DIFFRACTION	2.01
4CA0	X-RAY DIFFRACTION	2.26
4AJ5	X-RAY DIFFRACTION	3.32

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96BD8-F1	85.95	0.74

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 (3): 242, 2, 157

Mutagenesis-validated functional residues (11):

Position	Phenotype
95–96	abolishes binding to mapre1.
155	decreases microtubule binding; when associated with a-236 and a-245.
183–184	decreases microtubule binding; when associated with 203-a–a-206.
185	phosphomimetic mutant which strongly reduces microtubule binding; when associated with d-205 or d-242.
203–206	decreases microtubule binding; when associated with 183-a–a-184.
205	phosphomimetic mutant which strongly reduces microtubule binding; when associated with d-185.
217	decreases microtubule binding; when associated with 223-a–a-227.
223–227	decreases microtubule binding; when associated with a-217.
236	decreases microtubule binding; when associated with a-155 and a-245.
242	phosphomimetic mutant which strongly reduces microtubule binding; when associated with d-185.
245	decreases microtubule binding; when associated with a-155 and a-236.

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: 276 (showing top): GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, GOBP_CHROMOSOME_ORGANIZATION, GOBP_ESTABLISHMENT_OF_SPINDLE_ORIENTATION, GOBP_POSITIVE_REGULATION_OF_MITOTIC_NUCLEAR_DIVISION, GOBP_ATTACHMENT_OF_SPINDLE_MICROTUBULES_TO_KINETOCHORE, GOBP_REGULATION_OF_CELL_CYCLE_CHECKPOINT, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_REGULATION_OF_NUCLEAR_DIVISION, GOBP_SPINDLE_LOCALIZATION, GOBP_CHROMOSOME_LOCALIZATION, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_POSITIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN

GO Biological Process (16): 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), positive regulation of microtubule polymerization (GO:0031116), establishment of meiotic spindle orientation (GO:0051296), cell division (GO:0051301), metaphase chromosome alignment (GO:0051310), attachment of mitotic spindle microtubules to kinetochore (GO:0051315), negative regulation of mitotic spindle assembly checkpoint signaling (GO:0140499), nuclear division (GO:0000280), establishment of localization in cell (GO:0051649), establishment of organelle localization (GO:0051656), nuclear chromosome segregation (GO:0098813)

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

GO Cellular Component (20): kinetochore (GO:0000776), outer kinetochore (GO:0000940), nucleoplasm (GO:0005654), centrosome (GO:0005813), cytosol (GO:0005829), spindle microtubule (GO:0005876), cilium (GO:0005929), microtubule cytoskeleton (GO:0015630), centriolar satellite (GO:0034451), ciliary basal body (GO:0036064), intercellular bridge (GO:0045171), mitotic spindle (GO:0072686), SKA complex (GO:0170027), mitotic spindle microtubule (GO:1990498), 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
cellular anatomical structure	5
intracellular membraneless organelle	4
mitotic cell cycle process	3
mitotic nuclear division	2
establishment of localization	2
protein-containing complex	2
microtubule organizing center	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
positive regulation of microtubule polymerization or depolymerization	1
regulation of microtubule polymerization	1
positive regulation of protein polymerization	1
microtubule polymerization	1
positive regulation of supramolecular fiber organization	1
establishment of spindle orientation	1
establishment of meiotic spindle localization	1
meiotic cell cycle	1
cellular process	1
chromosome localization	1
nuclear chromosome segregation	1
mitotic metaphase chromosome alignment	1
attachment of spindle microtubules to kinetochore	1
mitotic spindle assembly checkpoint signaling	1
negative regulation of cell cycle process	1
positive regulation of mitotic metaphase/anaphase transition	1
positive regulation of mitotic sister chromatid segregation	1
negative regulation of spindle checkpoint	1
regulation of mitotic cell cycle spindle assembly checkpoint	1
organelle fission	1
cellular localization	1

Protein interactions and networks

STRING

1434 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SKA1	SKA2	Q8WVK7	996
SKA1	SKA3	Q8IX90	995
SKA1	NUF2	Q9BZD4	741
SKA1	SPC24	Q8NBT2	730
SKA1	KIF2C	Q99661	714
SKA1	CENPE	Q02224	704
SKA1	NDC80	O14777	683
SKA1	CENPA	P49450	681
SKA1	AURKB	Q96GD4	675
SKA1	CENPI	Q92674	656
SKA1	KIF18A	Q8NI77	628
SKA1	KNL1	Q8NG31	623
SKA1	CENPM	Q9NSP4	620
SKA1	ZW10	O43264	618
SKA1	DLGAP5	Q15398	618

IntAct

109 interactions, top by confidence:

A	B	Type	Score
SKA1	SKA3	psi-mi:“MI:0915”(physical association)	0.930
SKA3	SKA1	psi-mi:“MI:0915”(physical association)	0.930
SKA3	SKA1	psi-mi:“MI:0403”(colocalization)	0.930
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
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
BLOC1S6	SKA1	psi-mi:“MI:0915”(physical association)	0.870
SKA1	BLOC1S6	psi-mi:“MI:0915”(physical association)	0.870
SKA2	SKA3	psi-mi:“MI:0914”(association)	0.830
SKA3	SKA2	psi-mi:“MI:0914”(association)	0.830
PSMC5	SKA1	psi-mi:“MI:0915”(physical association)	0.800
PSMC5	PSMD11	psi-mi:“MI:0914”(association)	0.730
PPP2R2C	PPP2R1A	psi-mi:“MI:0914”(association)	0.730
SKA1	FAM9C	psi-mi:“MI:0915”(physical association)	0.670
FAM9C	SKA1	psi-mi:“MI:0915”(physical association)	0.670
FAM9C	NDC80	psi-mi:“MI:0914”(association)	0.670

BioGRID (106): SKA1 (Two-hybrid), SKA1 (Two-hybrid), SKA1 (Affinity Capture-MS), SKA1 (Affinity Capture-MS), SKA1 (Affinity Capture-MS), SKA1 (Two-hybrid), SKA1 (Affinity Capture-MS), LINC00521 (Two-hybrid), SKA1 (Affinity Capture-MS), SKA1 (Affinity Capture-MS), SKA1 (Proximity Label-MS), SKA1 (Proximity Label-MS), SKA1 (Proximity Label-MS), SKA1 (Proximity Label-MS), DSC2 (Affinity Capture-MS)

ESM2 similar proteins: A2AU37, A5LFW4, A6QNM3, A6QPC8, A9SV60, A9SY64, B0BN28, C0SV12, C6KIE6, F4JET1, O15013, O60566, O65312, O82504, P43124, Q0V7M7, Q10SU5, Q24168, Q28GV1, Q2RBJ4, Q2TBI1, Q3V124, Q4V3E2, Q4V8G2, Q5H9L4, Q5RH01, Q60862, Q641G4, Q6AUQ7, Q75PQ8, Q86VD1, Q8C5W4, Q8H1E8, Q8N140, Q91628, Q96BD8, Q9C689, Q9CPV1, Q9FJX9, Q9LUR0

Diamond homologs: B0BM28, B0BN28, Q0V7M7, Q6DHG8, Q96BD8, Q9CPV1, Q9XWS0, B4FGS2, B8B624, Q7XAM0, Q9LZZ7, A8WS92

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
AURKB	“up-regulates activity”	SKA1	phosphorylation
SKA1	“form complex”	“SKA complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 73 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
RHOQ GTPase cycle	5	22.1×	4e-04
Loss of Nlp from mitotic centrosomes	5	19.3×	4e-04
Loss of proteins required for interphase microtubule organization from the centrosome	5	19.3×	4e-04
AURKA Activation by TPX2	5	18.6×	5e-04
Recruitment of mitotic centrosome proteins and complexes	5	16.6×	7e-04
Regulation of PLK1 Activity at G2/M Transition	5	15.5×	8e-04
Recruitment of NuMA to mitotic centrosomes	5	14.2×	9e-04
Anchoring of the basal body to the plasma membrane	5	13.8×	9e-04

GO biological processes:

GO term	Partners	Fold	FDR
chromosome segregation	6	18.6×	1e-04
mitotic cell cycle	6	14.3×	4e-04
cilium assembly	6	7.9×	4e-03
cell division	8	6.6×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	20
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

804 predictions. Top by Δscore:

Variant	Effect	Δscore
18:50375183:G:GT	donor_gain	1.0000
18:50375815:TTCA:T	acceptor_loss	1.0000
18:50375816:TCA:T	acceptor_loss	1.0000
18:50375817:CA:C	acceptor_loss	1.0000
18:50375818:A:AG	acceptor_gain	1.0000
18:50375818:AGAG:A	acceptor_gain	1.0000
18:50375819:G:GA	acceptor_loss	1.0000
18:50375819:G:GG	acceptor_gain	1.0000
18:50375819:GA:G	acceptor_gain	1.0000
18:50375819:GAGG:G	acceptor_gain	1.0000
18:50375819:GAGGC:G	acceptor_gain	1.0000
18:50375914:CTGTG:C	donor_gain	1.0000
18:50375916:GTG:G	donor_gain	1.0000
18:50375918:GGT:G	donor_loss	1.0000
18:50375919:G:GG	donor_gain	1.0000
18:50375920:TAA:T	donor_loss	1.0000
18:50382223:GCTG:G	donor_gain	1.0000
18:50385214:A:AG	acceptor_gain	1.0000
18:50385215:G:GA	acceptor_gain	1.0000
18:50385215:GT:G	acceptor_gain	1.0000
18:50385215:GTGTT:G	acceptor_gain	1.0000
18:50385299:G:GT	donor_gain	1.0000
18:50385310:G:GT	donor_gain	1.0000
18:50385354:G:GG	donor_gain	1.0000
18:50391118:TTACA:T	acceptor_loss	1.0000
18:50391119:TACA:T	acceptor_loss	1.0000
18:50391120:ACAG:A	acceptor_loss	1.0000
18:50391121:CAGGT:C	acceptor_loss	1.0000
18:50391123:G:GA	acceptor_loss	1.0000
18:50391123:GGTAC:G	acceptor_gain	1.0000

AlphaMissense

1682 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:50392107:T:C	F210L	0.994
18:50392109:T:A	F210L	0.994
18:50392109:T:G	F210L	0.994
18:50392186:G:C	R236P	0.994
18:50392231:G:C	R251P	0.994
18:50391199:A:C	K175N	0.993
18:50391199:A:T	K175N	0.993
18:50392230:C:A	R251S	0.993
18:50392111:T:A	I211K	0.991
18:50391198:A:T	K175I	0.990
18:50391137:C:A	R155S	0.989
18:50385347:T:A	V148D	0.986
18:50391197:A:G	K175E	0.986
18:50392199:G:C	R240S	0.986
18:50392199:G:T	R240S	0.986
18:50392201:T:C	L241P	0.985
18:50391138:G:C	R155P	0.984
18:50392108:T:C	F210S	0.982
18:50392188:C:G	H237D	0.981
18:50385323:T:A	I140K	0.980
18:50392122:G:C	D215H	0.980
18:50392213:G:C	R245P	0.979
18:50391185:G:C	A171P	0.977
18:50392111:T:G	I211R	0.977
18:50392183:T:C	L235S	0.977
18:50392185:C:G	R236G	0.976
18:50392201:T:G	L241R	0.976
18:50392230:C:G	R251G	0.976
18:50392233:T:G	Y252D	0.976
18:50392189:A:C	H237P	0.975

dbSNP variants (sampled 300 via entrez): RS1000159726 (18:50376177 T>A), RS1000680377 (18:50375805 T>C), RS1000906304 (18:50374778 C>T), RS1001043932 (18:50381316 G>C), RS1001285999 (18:50387316 C>G,T), RS1001666896 (18:50381804 C>T), RS1001739256 (18:50375341 C>G), RS1001773446 (18:50375090 G>C), RS1001950559 (18:50382056 C>T), RS1002071354 (18:50374081 A>G), RS1002103986 (18:50373875 C>A,G), RS1002159077 (18:50391352 G>A,C), RS1002222025 (18:50384531 T>C), RS1002228797 (18:50389597 A>G), RS1002387914 (18:50386943 G>T)

Disease associations

OMIM: gene MIM:616673 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST004862_115	Itch intensity from mosquito bite adjusted by bite size	5.000000e-06
GCST005497_15	Large HDL particle concentration	2.000000e-08
GCST005499_3	Phospholipid levels in large HDL	2.000000e-08
GCST005504_15	Phospholipid levels in medium HDL	4.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	2
Testosterone	affects cotreatment, decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Tretinoin	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	increases expression	1
propionaldehyde	decreases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, increases reaction	1
methylparaben	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	increases expression, affects cotreatment	1
polyhexamethyleneguanidine	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
deguelin	increases expression	1
2-palmitoylglycerol	increases expression	1
jinfukang	increases expression	1
incobotulinumtoxinA	decreases expression	1
Dasatinib	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects methylation	1
Azathioprine	decreases expression	1
Benzo(a)pyrene	increases expression	1
Calcitriol	decreases expression, affects cotreatment	1
Cisplatin	increases expression	1
Coumestrol	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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