Details of Drug Off-Target (DOT)

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

• DOT Name: Alpha-hemoglobin-stabilizing protein (AHSP)
• Synonyms: Erythroid differentiation-related factor; Erythroid-associated factor
• Gene Name: AHSP
• Related Disease:
  Anemia
  Atrial fibrillation
  Congestive heart failure
  Creutzfeldt Jacob disease
  Hematologic disease
  Obstructive sleep apnea
  Alpha thalassemia
  Fetal growth restriction
  Hemoglobin H disease
  Metastatic sarcoma
• UniProt ID: AHSP_HUMAN
• PDB ID: 1W09; 1W0A; 1W0B; 1XZY; 1Y01; 1Z8U; 3IA3; 3OVU
• Pfam ID: PF09236
• Sequence:
  MALLKANKDLISAGLKEFSVLLNQQVFNDPLVSEEDMVTVVEDWMNFYINYYRQQVTGEP
  QERDKALQELRQELNTLANPFLAKYRDFLKSHELPSHPPPSS
• Function: Acts as a chaperone to prevent the harmful aggregation of alpha-hemoglobin during normal erythroid cell development. Specifically protects free alpha-hemoglobin from precipitation. It is predicted to modulate pathological states of alpha-hemoglobin excess such as beta-thalassemia.
• Tissue Specificity: Expressed in blood and bone marrow.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Anemia	DISTVL0C	Strong	Biomarker	[1]
Atrial fibrillation	DIS15W6U	Strong	Biomarker	[2]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[3]
Creutzfeldt Jacob disease	DISCB6RX	Strong	Biomarker	[4]
Hematologic disease	DIS9XD9A	Strong	Altered Expression	[4]
Obstructive sleep apnea	DIS0SVD1	Strong	Biomarker	[2]
Alpha thalassemia	DIS5XGK0	moderate	Biomarker	[5]
Fetal growth restriction	DIS5WEJ5	moderate	Altered Expression	[6]
Hemoglobin H disease	DISHFWO5	moderate	Altered Expression	[5]
Metastatic sarcoma	DISKYC7V	moderate	Biomarker	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Alpha-hemoglobin-stabilizing protein (AHSP).	[8]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Alpha-hemoglobin-stabilizing protein (AHSP).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Alpha-hemoglobin-stabilizing protein (AHSP).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Alpha-hemoglobin-stabilizing protein (AHSP).	[11]

References

• [1] Transgenic human alpha-hemoglobin stabilizing protein could partially relieve betaIVS-2-654-thalassemia syndrome in model mice.Hum Gene Ther. 2010 Feb;21(2):149-56. doi: 10.1089/hum.2009.132.
• [2] Patient characteristics as predictors of recurrence of atrial fibrillation following cryoballoon ablation.Pacing Clin Electrophysiol. 2019 Jun;42(6):694-704. doi: 10.1111/pace.13669. Epub 2019 Apr 9.
• [3] Endothelial dysfunction in the pulmonary vascular bed.Am J Med Sci. 2000 Oct;320(4):223-32. doi: 10.1097/00000441-200010000-00001.
• [4] alpha-Hemoglobin stabilizing protein is not a suitable marker for a screening test for variant Creutzfeldt-Jakob disease.Transfusion. 2008 Aug;48(8):1616-26. doi: 10.1111/j.1537-2995.2008.01759.x. Epub 2008 May 22.
• [5] A molecular study on the role of alpha-hemoglobin-stabilizing protein in hemoglobin H disease.Ann Hematol. 2017 Jun;96(6):1005-1014. doi: 10.1007/s00277-017-2978-x. Epub 2017 Mar 23.
• [6] Alpha-hemoglobin-stabilizing protein (AHSP) in hemolysis, elevated liver enzyme, and low platelet (HELLP) syndrome, intrauterine growth restriction (IUGR) and fetal death.Cell Stress Chaperones. 2008 Spring;13(1):67-71. doi: 10.1007/s12192-008-0009-5. Epub 2008 Feb 6.
• [7] -Hemoglobin-stabilizing Protein: An Effective Marker for Erythroid Precursors in Bone Marrow Biopsy Specimens.Appl Immunohistochem Mol Morphol. 2016 Jan;24(1):51-6. doi: 10.1097/PAI.0000000000000139.
• [8] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [9] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [10] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [11] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.