SKIC2 (SKI2 subunit of superkiller complex)

Gene

• Entrez ID: 6499
• Gene name: SKI2 subunit of superkiller complex
• Gene symbol: SKIC2
• Synonyms (NCBI Gene): 170A, DDX13, HLP, SKI2, SKI2W, SKIV2, SKIV2L, SKIV2L1, THES2
• Chromosome: 6
• Chromosome location: 6p21.33

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs200818962	C>T	Uncertain-significance, pathogenic	Coding sequence variant, stop gained, non coding transcript variant
rs750250320	C>T	Likely-pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs751026211	G>A	Pathogenic	Stop gained, non coding transcript variant, coding sequence variant
rs766089213	G>-	Pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant
rs768503878	C>T	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, stop gained, non coding transcript variant
rs781544014	C>T	Likely-pathogenic	Non coding transcript variant, 3 prime UTR variant, stop gained, coding sequence variant
rs781763471	A>G	Pathogenic	Splice acceptor variant
rs1562659544	->A	Pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant
rs1582171003	G>-	Not-provided, pathogenic	Stop gained, coding sequence variant, non coding transcript variant
rs1582187890	->A	Likely-pathogenic	Coding sequence variant, frameshift variant, non coding transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT051423	hsa-let-7e-5p	CLASH	23622248
MIRT046701	hsa-miR-222-3p	CLASH	23622248
MIRT1351228	hsa-miR-3675-5p	CLIP-seq
MIRT1351229	hsa-miR-4307	CLIP-seq
MIRT1351230	hsa-miR-4666-5p	CLIP-seq
MIRT1351231	hsa-miR-4802-3p	CLIP-seq
MIRT1351232	hsa-miR-486-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0003676	Function	Nucleic acid binding	IEA
GO:0003723	Function	RNA binding	IEA
GO:0003724	Function	RNA helicase activity	IBA
GO:0003724	Function	RNA helicase activity	IEA
GO:0003724	Function	RNA helicase activity	TAS	7610041
GO:0004386	Function	Helicase activity	IEA
GO:0005515	Function	Protein binding	IPI	32296183
GO:0005524	Function	ATP binding	IEA
GO:0005634	Component	Nucleus	IEA
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	TAS
GO:0006401	Process	RNA catabolic process	IEA
GO:0016787	Function	Hydrolase activity	IEA
GO:0016887	Function	ATP hydrolysis activity	IEA
GO:0034458	Function	3'-5' RNA helicase activity	IDA	35120588
GO:0055087	Component	Ski complex	IBA
GO:0055087	Component	Ski complex	IDA	16024656, 32006463, 35120588
GO:0070478	Process	Nuclear-transcribed mRNA catabolic process, 3'-5' exonucleolytic nonsense-mediated decay	IBA
GO:0070478	Process	Nuclear-transcribed mRNA catabolic process, 3'-5' exonucleolytic nonsense-mediated decay	IDA	32006463, 35120588
GO:0072344	Process	Rescue of stalled ribosome	IDA	32006463

Other IDs

• MIM: 600478
• HGNC: 10898
• e!Ensembl: ENSG00000204351

Protein

• UniProt ID: Q15477
• Protein name: Superkiller complex protein 2 (Ski2) (EC 3.6.4.13) (Helicase-like protein) (HLP)
• Protein function: Helicase component of the SKI complex, a multiprotein complex that assists the RNA-degrading exosome during the mRNA decay and quality-control pathways (PubMed:16024656, PubMed:32006463, PubMed:35120588). The SKI complex catalyzes mRNA extractio
• PDB: 7QDR, 7QDS, 7QDY, 7QDZ, 7QE0, 9G8M, 9G8N, 9G8O, 9G8P, 9G8Q, 9G8R
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF17911	Ski2_N	74 → 203	Ski2 N-terminal region	Domain
  PF00270	DEAD	312 → 463	DEAD/DEAH box helicase	Domain
  PF00271	Helicase_C	563 → 708	Helicase conserved C-terminal domain	Family
  PF13234	rRNA_proc-arch	763 → 1046	rRNA-processing arch domain	Domain
  PF08148	DSHCT	1071 → 1240	DSHCT (NUC185) domain	Domain

• Sequence:

  MMETERLVLPPPDPLDLPLRAVELGCTGHWELLNLPGAPESSLPHGLPPCAPDLQQEAEQ
  LFLSSPAWLPLHGVEHSARKWQRKTDPWSLLAVLGAPVPSDLQAQRHPTTGQILGYKEVL
  LENTNLSATTSLSLRRPPGPASQSLWGNPTQYPFWPGGMDEPTITDLNTREEAEEEIDFE
  KDLLTIPPGFKKGMDFAPKDCPTPAPGLLSLSCMLEPLDLGGGDEDENEAVGQPGGPRGD
  TVSASPCSAPLARASSLEDLVLKEASTAVSTPEAPEPPSQEQWAIPVDATSPVGDFYRLI
  PQPAFQWAFEPDVFQKQAILHLERHDSVFVAAHTSAGKTVVAEYAIALAQKHMTRTIYTS
  PIKALSNQKFRDFRNTFGDVGLLTGDVQLHPEASCLIMTTEILRSMLYSGSDVIRDLEWV
  IFDEVHYINDVERGVVWEEVLIMLPDHVSIILLSATVPNALEFADWIGRLKRRQIYVIST
  VTRPVPLEHYLFTGNSSKTQGELFLLLDSRGAFHTKGYYAAVEAKKERMSKHAQTFGAKQ
  PTHQGGPAQDRGVYLSLLASLRTRAQLPVVVFTFSRGRCDEQASGLTSLDLTTSSEKSEI
  HLFLQRCLARLRGSDRQLPQVLHMSELLNRGLGVHHSGILPILKEIVEMLFSRGLVKVLF
  ATETFAMGVNMPARTVVFDSMRKHDGSTFRDLLPGEYVQMAGRAGRRGLDPTGTVILLCK
  GRVPEMADLHRMMMGKPSQLQSQFRLTYTMILNLLRVDALRVEDMMKRSFSEFPSRKDSK
  AHEQALAELTKRLGALEEPDMTGQLVDLPEYYSWGEELTETQHMIQRRIMESVNGLKSLS
  AGRVVVVKNQEHHNALGVILQVSSNSTSRVFTTLVLCDKPLSQDPQDRGPATAEVPYPDD
  LVGFKLFLPEGPCDHTVVKLQPGDMAAITTKVLRVNGEKILEDFSKRQQPKFKKDPPLAA
  VTTAVQELLRLAQAHPAGPPTLDPVNDLQLKDMSVVEGGLRARKLEELIQGAQCVHSPRF
  PAQYLKLRERMQIQKEMERLRFLLSDQSLLLLPEYHQRVEVLRTLGYVDEAGTVKLAGRV
  ACAMSSHELLLTELMFDNALSTLRPEEIAALLSGLVCQSPGDAGDQLPNTLKQGIERVRA
  VAKRIGEVQVACGLNQTVEEFVGELNFGLVEVVYEWARGMPFSELAGLSGTPEGLVVRCI
  QRLAEMCRSLRGAARLVGEPVLGAKMETAATLLRRDIVFAASLYTQ

• Sequence length: 1246

Pathways

KEGG:

RNA degradation

Reactome:

mRNA decay by 3' to 5' exoribonuclease

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Gastric cancer	Likely pathogenic	rs762751779	RCV005912589	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Immunodeficiency 57	Pathogenic	rs767084483	RCV004999788	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Ovarian serous cystadenocarcinoma	Likely pathogenic	rs1419680561, rs1375849231	RCV005934624 RCV005936616	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
SKIC2-related disorder	Pathogenic; Likely pathogenic	rs138923214, rs1353707093, rs200818962, rs2482913862, rs2482998760, rs751026211	RCV003956370 RCV003407950 RCV004752805 RCV003429065 RCV003911543 RCV003390696	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Trichohepatoenteric syndrome	Pathogenic; Likely pathogenic	rs138923214, rs759511516, rs200271795, rs1772636752, rs2483002672, rs1244156082, rs899709021, rs377014444, rs2482913862	RCV003155429 RCV003155397 RCV001844644 RCV002240109 RCV002470082 RCV003123466 RCV003155841 RCV003226784 RCV006269838	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Trichohepatoenteric syndrome 2	Pathogenic; Likely pathogenic	rs138923214, rs759511516, rs1772848223, rs750724648, rs1772679892, rs2482893792, rs1475859257, rs200818962, rs144714933, rs969421193, rs751026211, rs281875237, rs1562659544, rs781763471, rs768503878, rs1582187890, rs1582192007, rs751074844, rs770099418, rs1772611373, rs1772638226	RCV001784970 RCV001543362 RCV001733641 RCV001784971 RCV002290870 RCV002471515 RCV005356245 RCV000778788 RCV003387668 RCV005250319 RCV000022972 RCV000022973 RCV000022974 RCV000680097 RCV000778787 RCV000850156 RCV000985128 RCV001089505 RCV001089506 RCV001257082 RCV001257083	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Uterine corpus endometrial carcinoma	Pathogenic	rs144714933	RCV005931445	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ATROPHIC MACULAR DEGENERATION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CANDIDEMIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CORONARY ARTERY DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEGENERATION OF MACULA AND POSTERIOR POLE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GLAUCOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
IMMUNODEFICIENCY 57 WITH AUTOINFLAMMATION	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MACULAR DEGENERATION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MIGRAINE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MOUTH NEOPLASM	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NON-ALCOHOLIC FATTY LIVER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PSORIATIC ARTHRITIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Uncertain significance; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uveal melanoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
WET MACULAR DEGENERATION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Age related macular degeneration	Age-related macular degeneration	BEFREE	19556007, 20861866, 23260260, 24865191, 24995509, 26861912, 27484132, 28173125, 29346644		★☆☆☆☆ Found in Text Mining only
Age related macular degeneration	Age-related macular degeneration	GWASCAT_DG	20385819, 20861866, 23455636, 23577725, 26691988, 29346644		★☆☆☆☆ Found in Text Mining only
Age related macular degeneration	Age-related macular degeneration	GWASDB_DG	20385819, 20861866, 21909106, 22694956, 23455636, 23577725		★☆☆☆☆ Found in Text Mining only
Aortic Valve Insufficiency	Aortic Valve Insufficiency	HPO_DG			★☆☆☆☆ Found in Text Mining only
Arthritis, Psoriatic	Psoriatic Arthritis	GWASCAT_DG	30552173		★☆☆☆☆ Found in Text Mining only
Asthma	Asthma	Pubtator	32817007	Associate	★☆☆☆☆ Found in Text Mining only
Atrial Septal Defects	Atrial Septal Defect	HPO_DG			★☆☆☆☆ Found in Text Mining only
Autoimmune Diseases	Autoimmune disease	Pubtator	7610041	Associate	★☆☆☆☆ Found in Text Mining only
Bicuspid aortic valve	Bicuspid aortic valve	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cirrhosis	Cirrhosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Clastothrix	Clastothrix	HPO_DG			★☆☆☆☆ Found in Text Mining only
Colitis	Colitis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	30555277		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	UNIPROT_DG			★☆☆☆☆ Found in Text Mining only
Congenital hypoplasia of kidney	Renal hypoplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital hypoplasia of thymus	Congenital Hypoplasia Of Thymus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Coronary heart disease	Coronary Heart Disease	GWASDB_DG	21971053		★☆☆☆☆ Found in Text Mining only
Craniocerebral Trauma	Craniocerebral trauma	Pubtator	29145277	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus Type 2	Diabetes mellitus, type 2	Pubtator	35601016	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Insulin-Dependent	Diabetes Mellitus	GWASDB_DG	17632545		★☆☆☆☆ Found in Text Mining only
Diarrhea	Diarrhea	Pubtator	29145277	Associate	★☆☆☆☆ Found in Text Mining only
Dubowitz syndrome	Dubowitz syndrome	Pubtator	33098347	Associate	★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Exudative age-related macular degeneration	Exudative Macular Degeneration	BEFREE	23260260, 24865191		★☆☆☆☆ Found in Text Mining only
Exudative age-related macular degeneration	Exudative Macular Degeneration	GWASCAT_DG	26691988		★☆☆☆☆ Found in Text Mining only
exudative macular degeneration	Exudative macular degeneration	GWASCAT_DG	26691988		★☆☆☆☆ Found in Text Mining only
Facial Dysmorphism with Multiple Malformations	Facial dysmorphism syndrome	Pubtator	29145277	Associate	★☆☆☆☆ Found in Text Mining only
Fibrosis, Liver	Liver Fibrosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Gastritis	Gastritis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Geographic Atrophy	Geographic Atrophy	GWASCAT_DG	26691988		★☆☆☆☆ Found in Text Mining only
Glaucoma	Glaucoma	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Glycogen storage disease type II	Glycogen Storage Disease	BEFREE	23260260, 24865191, 26861912		★☆☆☆☆ Found in Text Mining only
Hepatoblastoma	Hepatoblastoma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypothyroidism	Hypothyroidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Immune System Diseases	Immune System Diseases	GENOMICS_ENGLAND_DG	28944135		★☆☆☆☆ Found in Text Mining only
Immunologic Deficiency Syndromes	Immunologic Deficiency Syndromes	HPO_DG			★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Intellectual developmental disorder	Pubtator	29145277	Associate	★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	23545258		★☆☆☆☆ Found in Text Mining only
Liver Cirrhosis	Liver cirrhosis	Pubtator	29145277	Associate	★☆☆☆☆ Found in Text Mining only
Liver Diseases	Liver disease	Pubtator	23679950, 29145277	Associate	★☆☆☆☆ Found in Text Mining only
Liver neoplasms	Liver neoplasms	BEFREE	23545258		★☆☆☆☆ Found in Text Mining only
Lupus Erythematosus Systemic	Systemic lupus erythematosus	Pubtator	17997607, 21067287	Associate	★☆☆☆☆ Found in Text Mining only
Lupus Erythematosus, Systemic	Lupus Erythematosus	BEFREE	11487501, 21067287		★☆☆☆☆ Found in Text Mining only
Lupus Erythematosus, Systemic	Lupus Erythematosus	GWASDB_DG	24871463		★☆☆☆☆ Found in Text Mining only
Lymphopenia	Lymphopenia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Macular Degeneration	Macular degeneration	Pubtator	20861866, 26861912, 29346644, 32346038, 33320170	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Macular Degeneration	Macular degeneration	Pubtator	20861866, 26861912	Inhibit	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant neoplasm of breast	Breast Cancer	UNIPROT_DG			★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	22469881		★☆☆☆☆ Found in Text Mining only
Mild Mental Retardation	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Mouth Neoplasms	Mouth neoplasm	Pubtator	36769103	Associate	★☆☆☆☆ Found in Text Mining only
Multiple Myeloma	Multiple myeloma	BEFREE	27697999		★☆☆☆☆ Found in Text Mining only
Multiple Sclerosis	Multiple Sclerosis	GWASDB_DG	20598377		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	24337110		★☆☆☆☆ Found in Text Mining only
Patent ductus arteriosus	Patent ductus arteriosus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Peripheral pulmonary artery stenosis	Peripheral pulmonary artery stenosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Polycystic Kidney Diseases	Polycystic kidney disease	HPO_DG			★☆☆☆☆ Found in Text Mining only
Primary biliary cirrhosis	Biliary Cirrhosis	GWASCAT_DG	30854688		★☆☆☆☆ Found in Text Mining only
Rheumatoid Arthritis	Rheumatoid arthritis	GWASDB_DG	17804836, 19503088, 21156761		★☆☆☆☆ Found in Text Mining only
Tetralogy of Fallot	Tetralogy of Fallot	HPO_DG			★☆☆☆☆ Found in Text Mining only
Thrombocytosis	Thrombocytosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Trichohepatoenteric Syndrome	Trichohepatoenteric Syndrome	BEFREE	22444670, 25714577, 27050310, 27431780, 29145277, 29484573, 29527791		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Trichohepatoenteric Syndrome	Trichohepatoenteric Syndrome	ORPHANET_DG	22444670, 23302111		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Trichohepatoenteric Syndrome	Trichohepatoenteric syndrome	Pubtator	22444670, 29484573, 29868001, 34414925	Associate	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Trichohepatoenteric Syndrome	Trichohepatoenteric Syndrome	GENOMICS_ENGLAND_DG	28944135		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Trichohepatoenteric Syndrome	Trichohepatoenteric Syndrome	CTD_human_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
TRICHOHEPATOENTERIC SYNDROME 2	Trichohepatoenteric Syndrome	UNIPROT_DG	22444670		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
TRICHOHEPATOENTERIC SYNDROME 2	Trichohepatoenteric Syndrome	GENOMICS_ENGLAND_DG	27537055, 28944135		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
TRICHOHEPATOENTERIC SYNDROME 2	Trichohepatoenteric Syndrome	CLINVAR_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Ventricular Septal Defects	Ventricular septal defect	HPO_DG			★☆☆☆☆ Found in Text Mining only