Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCN25R5)

• DOT Name: Mineralization regulator ANKH (ANKH)
• Synonyms: ATP carrier protein ANKH; Progressive ankylosis protein homolog; ANK
• Gene Name: ANKH
• Related Disease:
  Chondrocalcinosis
  Chondrocalcinosis 2
  Craniodiaphyseal dysplasia, autosomal dominant
  Cranioectodermal dysplasia 3
  Cranioectodermal dysplasia 4
  Craniometaphyseal dysplasia, autosomal dominant
  Craniometaphyseal dysplasia, autosomal recessive
  Deafness
  Metabolic disorder
  Ankylosing spondylitis
  Arthritis
  Autism
  Bone disease
  Campomelic dysplasia
  Epilepsy
  Glaucoma/ocular hypertension
  Hypophosphatemia
  Kidney failure
  MASS syndrome
  Non-insulin dependent diabetes
  Obesity
  Open-angle glaucoma
  Osteoarthritis
  Pyle disease
  Arthropathy
  Bloom syndrome
  Pseudoxanthoma elasticum
  Rheumatoid arthritis
  Craniometaphyseal dysplasia
  Endometriosis
  Chronic renal failure
  Osteoporosis
• UniProt ID: ANKH_HUMAN
• Pfam ID: PF07260
• Sequence:
  MVKFPALTHYWPLIRFLVPLGITNIAIDFGEQALNRGIAAVKEDAVEMLASYGLAYSLMK
  FFTGPMSDFKNVGLVFVNSKRDRTKAVLCMVVAGAIAAVFHTLIAYSDLGYYIINKLHHV
  DESVGSKTRRAFLYLAAFPFMDAMAWTHAGILLKHKYSFLVGCASISDVIAQVVFVAILL
  HSHLECREPLLIPILSLYMGALVRCTTLCLGYYKNIHDIIPDRSGPELGGDATIRKMLSF
  WWPLALILATQRISRPIVNLFVSRDLGGSSAATEAVAILTATYPVGHMPYGWLTEIRAVY
  PAFDKNNPSNKLVSTSNTVTAAHIKKFTFVCMALSLTLCFVMFWTPNVSEKILIDIIGVD
  FAFAELCVVPLRIFSFFPVPVTVRAHLTGWLMTLKKTFVLAPSSVLRIIVLIASLVVLPY
  LGVHGATLGVGSLLAGFVGESTMVAIAACYVYRKQKKKMENESATEGEDSAMTDMPPTEE
  VTDIVEMREENE
• Function: Transports adenosine triphosphate (ATP) and possibly other nucleoside triphosphates (NTPs) from cytosol to the extracellular space. Mainly regulates their levels locally in peripheral tissues while playing a minor systemic role. Prevents abnormal ectopic mineralization of the joints by regulating the extracellular levels of the calcification inhibitor inorganic pyrophosphate (PPi), which originates from the conversion of extracellular NTPs to NMPs and PPis by ENPP1. Regulates the release of the TCA cycle intermediates to the extracellular space, in particular citrate, succinate and malate. Extracellular citrate mostly present in bone tissue is required for osteogenic differentiation of mesenchymal stem cells, stabilization of hydroxyapatite structure and overall bone strength. The transport mechanism remains to be elucidated (Probable).
• Tissue Specificity: Found in osteoblasts from mandibular bone and from iliac bone; not detected in osteoclastic cells.
• Reactome Pathway: Miscellaneous transport and binding events (R-HSA-5223345)

Molecular Interaction Atlas (MIA) of This DOT

32 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chondrocalcinosis	DISP4AHX	Definitive	Biomarker	[1]
Chondrocalcinosis 2	DISZDQIW	Definitive	Autosomal dominant	[2]
Craniodiaphyseal dysplasia, autosomal dominant	DIS2YXJ1	Definitive	Biomarker	[3]
Cranioectodermal dysplasia 3	DIS5TX0M	Definitive	Biomarker	[3]
Cranioectodermal dysplasia 4	DISQDMZW	Definitive	Biomarker	[3]
Craniometaphyseal dysplasia, autosomal dominant	DISU12OO	Definitive	Autosomal dominant	[4]
Craniometaphyseal dysplasia, autosomal recessive	DISXHFIL	Definitive	Biomarker	[3]
Deafness	DISKCLH4	Definitive	Genetic Variation	[5]
Metabolic disorder	DIS71G5H	Definitive	Genetic Variation	[5]
Ankylosing spondylitis	DISRC6IR	Strong	Genetic Variation	[6]
Arthritis	DIST1YEL	Strong	Genetic Variation	[7]
Autism	DISV4V1Z	Strong	Biomarker	[8]
Bone disease	DISE1F82	Strong	Biomarker	[9]
Campomelic dysplasia	DISVTW53	Strong	Altered Expression	[10]
Epilepsy	DISBB28L	Strong	Biomarker	[11]
Glaucoma/ocular hypertension	DISLBXBY	Strong	Genetic Variation	[12]
Hypophosphatemia	DIS9DZYF	Strong	Genetic Variation	[13]
Kidney failure	DISOVQ9P	Strong	Biomarker	[14]
MASS syndrome	DISI3721	Strong	Genetic Variation	[15]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[16]
Obesity	DIS47Y1K	Strong	Biomarker	[17]
Open-angle glaucoma	DISSZEE8	Strong	Genetic Variation	[18]
Osteoarthritis	DIS05URM	Strong	Genetic Variation	[19]
Pyle disease	DISJ2YQ3	Strong	Genetic Variation	[20]
Arthropathy	DISVEERK	moderate	Altered Expression	[21]
Bloom syndrome	DISKXQ7J	moderate	Biomarker	[22]
Pseudoxanthoma elasticum	DIS8WUQG	moderate	Altered Expression	[23]
Rheumatoid arthritis	DISTSB4J	moderate	Genetic Variation	[24]
Craniometaphyseal dysplasia	DISK6EZQ	Supportive	Autosomal dominant	[25]
Endometriosis	DISX1AG8	Disputed	Biomarker	[26]
Chronic renal failure	DISGG7K6	Limited	Altered Expression	[27]
Osteoporosis	DISF2JE0	Limited	Genetic Variation	[28]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Mineralization regulator ANKH (ANKH).	[29]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Mineralization regulator ANKH (ANKH).	[34]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Mineralization regulator ANKH (ANKH).	[40]

18 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 Mineralization regulator ANKH (ANKH).	[30]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Mineralization regulator ANKH (ANKH).	[31]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Mineralization regulator ANKH (ANKH).	[32]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Mineralization regulator ANKH (ANKH).	[33]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Mineralization regulator ANKH (ANKH).	[35]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Mineralization regulator ANKH (ANKH).	[36]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Mineralization regulator ANKH (ANKH).	[37]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Mineralization regulator ANKH (ANKH).	[36]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Mineralization regulator ANKH (ANKH).	[38]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Mineralization regulator ANKH (ANKH).	[24]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Mineralization regulator ANKH (ANKH).	[39]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Mineralization regulator ANKH (ANKH).	[41]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Mineralization regulator ANKH (ANKH).	[42]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Mineralization regulator ANKH (ANKH).	[39]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Mineralization regulator ANKH (ANKH).	[43]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Mineralization regulator ANKH (ANKH).	[44]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Mineralization regulator ANKH (ANKH).	[45]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Mineralization regulator ANKH (ANKH).	[46]

References

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