Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3WGZ73)

• DOT Name: Cytospin-A (SPECC1L)
• Synonyms: Renal carcinoma antigen NY-REN-22; Sperm antigen with calponin homology and coiled-coil domains 1-like; SPECC1-like protein
• Gene Name: SPECC1L
• Related Disease:
  Obsolete hypertelorism, Teebi type
  Intellectual disability
  Neoplasm
  Obsolete autosomal dominant Opitz G/BBB syndrome
  Tessier number 4 facial cleft
  X-linked Opitz G/BBB syndrome
  Facial cleft
  Commissural facial cleft
  DiGeorge syndrome
  Oculomaxillofacial dysostosis
  Teebi hypertelorism syndrome
• UniProt ID: CYTSA_HUMAN
• Pfam ID: PF00307
• Sequence:
  MKKASRSVGSVPKVSAISKTQTAEKIKPENSSSASTGGKLVKPGTAASLSKTKSSDDLLA
  GMAGGVTVTNGVKGKKSTCPSAAPSASAPAMTTVENKSKISTGTASSTKRSTSTGNKESS
  STRERLRERTRLNQSKKLPSAGQGANDMALAKRSRSRTATECDVRMSKSKSDNQISDRAA
  LEAKVKDLLTLAKTKDVEILHLRNELRDMRAQLGINEDHSEGDEKSEKETIMAHQPTDVE
  STLLQLQEQNTAIREELNQLKNENRMLKDRLNALGFSLEQRLDNSEKLFGYQSLSPEITP
  GNQSDGGGTLTSSVEGSAPGSVEDLLSQDENTLMDHQHSNSMDNLDSECSEVYQPLTSSD
  DALDAPSSSESEGIPSIERSRKGSSGNASEVSVACLTERIHQMEENQHSTSEELQATLQE
  LADLQQITQELNSENERLGEEKVILMESLCQQSDKLEHFSRQIEYFRSLLDEHHISYVID
  EDVKSGRYMELEQRYMDLAENARFEREQLLGVQQHLSNTLKMAEQDNKEAQEMIGALKER
  SHHMERIIESEQKGKAALAATLEEYKATVASDQIEMNRLKAQLENEKQKVAELYSIHNSG
  DKSDIQDLLESVRLDKEKAETLASSLQEDLAHTRNDANRLQDAIAKVEDEYRAFQEEAKK
  QIEDLNMTLEKLRSDLDEKETERSDMKETIFELEDEVEQHRAVKLHDNLIISDLENTVKK
  LQDQKHDMEREIKTLHRRLREESAEWRQFQADLQTAVVIANDIKSEAQEEIGDLKRRLHE
  AQEKNEKLTKELEEIKSRKQEEERGRVYNYMNAVERDLAALRQGMGLSRRSSTSSEPTPT
  VKTLIKSFDSASQVPNPAAAAIPRTPLSPSPMKTPPAAAVSPMQRHSISGPISTSKPLTA
  LSDKRPNYGEIPVQEHLLRTSSASRPASLPRVPAMESAKTLSVSRRSSEEVKRDISAQEG
  ASPASLMAMGTTSPQLSLSSSPTASVTPTTRSRIREERKDPLSALAREYGGSKRNALLKW
  CQKKTEGYQNIDITNFSSSWNDGLAFCALLHTYLPAHIPYQELNSQDKRRNFMLAFQAAE
  SVGIKSTLDINEMVRTERPDWQNVMLYVTAIYKYFET
• Function: Involved in cytokinesis and spindle organization. May play a role in actin cytoskeleton organization and microtubule stabilization and hence required for proper cell adhesion and migration.

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Obsolete hypertelorism, Teebi type	DISTIPAM	Definitive	Autosomal dominant	[1]
Intellectual disability	DISMBNXP	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Obsolete autosomal dominant Opitz G/BBB syndrome	DISEKX4A	Strong	Autosomal dominant	[4]
Tessier number 4 facial cleft	DISUGPNI	Strong	Autosomal dominant	[5]
X-linked Opitz G/BBB syndrome	DISQ14EC	Strong	Genetic Variation	[1]
Facial cleft	DISXTTL9	moderate	Biomarker	[6]
Commissural facial cleft	DISYV18K	Supportive	Autosomal dominant	[5]
DiGeorge syndrome	DIST1RKO	Limited	Genetic Variation	[2]
Oculomaxillofacial dysostosis	DISG9E1R	Limited	Genetic Variation	[1]
Teebi hypertelorism syndrome	DIS6ZEUS	Limited	Genetic Variation	[7]

5 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cytospin-A (SPECC1L).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cytospin-A (SPECC1L).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Cytospin-A (SPECC1L).	[10]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Cytospin-A (SPECC1L).	[11]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Cytospin-A (SPECC1L).	[12]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Cytospin-A (SPECC1L).	[13]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Cytospin-A (SPECC1L).	[13]

References

• [1] Phenotypic spectrum associated with SPECC1L pathogenic variants: new families and critical review of the nosology of Teebi, Opitz GBBB, and Baraitser-Winter syndromes. Eur J Med Genet. 2019 Dec;62(12):103588. doi: 10.1016/j.ejmg.2018.11.022. Epub 2018 Nov 22.
• [2] Mutations in SPECC1L, encoding sperm antigen with calponin homology and coiled-coil domains 1-like, are found in some cases of autosomal dominant Opitz G/BBB syndrome.J Med Genet. 2015 Feb;52(2):104-10. doi: 10.1136/jmedgenet-2014-102677. Epub 2014 Nov 20.
• [3] Epithelioid fibrous histiocytoma: molecular characterization of ALK fusion partners in 23 cases.Mod Pathol. 2018 May;31(5):753-762. doi: 10.1038/modpathol.2017.191. Epub 2018 Jan 12.
• [4] PanelApp crowdsources expert knowledge to establish consensus diagnostic gene panels. Nat Genet. 2019 Nov;51(11):1560-1565. doi: 10.1038/s41588-019-0528-2.
• [5] Deficiency of the cytoskeletal protein SPECC1L leads to oblique facial clefting. Am J Hum Genet. 2011 Jul 15;89(1):44-55. doi: 10.1016/j.ajhg.2011.05.023. Epub 2011 Jun 23.
• [6] Functional analysis of SPECC1L in craniofacial development and oblique facial cleft pathogenesis.Plast Reconstr Surg. 2014 Oct;134(4):748-759. doi: 10.1097/PRS.0000000000000517.
• [7] Expanding the SPECC1L mutation phenotypic spectrum to include Teebi hypertelorism syndrome. Am J Med Genet A. 2015 Nov;167A(11):2497-502. doi: 10.1002/ajmg.a.37217. Epub 2015 Jun 25.
• [8] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [9] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [10] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [13] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.