DBH (dopamine beta-hydroxylase)

Gene

• Entrez ID: 1621
• Gene name: Dopamine beta-hydroxylase
• Gene symbol: DBH
• Synonyms: DBM, ORTHYP1
• Chromosome: 9
• Chromosome location: 9q34.2
• Summary: The protein encoded by this gene is an oxidoreductase belonging to the copper type II, ascorbate-dependent monooxygenase family. The encoded protein, expressed in neuroscretory vesicles and chromaffin granules of the adrenal medulla, catalyzes the convers

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs74853476	T>C	Pathogenic	Splice donor variant
rs75215331	C>A,T	Likely-benign, pathogenic	Missense variant, coding sequence variant
rs77576840	C>A,T	Pathogenic	Synonymous variant, missense variant, coding sequence variant
rs199926239	T>A,C	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Intron variant
rs267606760	G>A	Pathogenic	Missense variant, coding sequence variant
rs267606761	G>A	Pathogenic	Missense variant, coding sequence variant
rs863225244	A>-	Pathogenic	Coding sequence variant, frameshift variant
rs863225245	G>T	Pathogenic	Coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT017290	hsa-miR-335-5p	Microarray	18185580
MIRT923702	hsa-miR-3664-3p	CLIP-seq
MIRT923703	hsa-miR-421	CLIP-seq
MIRT923704	hsa-miR-4649-5p	CLIP-seq
MIRT923705	hsa-miR-4685-5p	CLIP-seq
MIRT923706	hsa-miR-4709-5p	CLIP-seq
MIRT923707	hsa-miR-4746-5p	CLIP-seq
MIRT923708	hsa-miR-505	CLIP-seq
MIRT923709	hsa-miR-510	CLIP-seq
MIRT923710	hsa-miR-512-5p	CLIP-seq
MIRT1973634	hsa-miR-4776-5p	CLIP-seq
MIRT2209190	hsa-miR-1908	CLIP-seq
MIRT2209191	hsa-miR-3180	CLIP-seq
MIRT2209192	hsa-miR-3180-3p	CLIP-seq
MIRT2209193	hsa-miR-3196	CLIP-seq
MIRT2209194	hsa-miR-4488	CLIP-seq
MIRT2209195	hsa-miR-4697-5p	CLIP-seq
MIRT2209196	hsa-miR-4781-5p	CLIP-seq
MIRT2209197	hsa-miR-503	CLIP-seq
MIRT2209198	hsa-miR-663	CLIP-seq
MIRT2209199	hsa-miR-744	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
HAND2	Activation	14512028
PHOX2A	Activation	16280598
PHOX2A	Unknown	11034547
PHOX2B	Activation	11034547;16280598
PHOX2B	Unknown	15888479
TFAP2A	Unknown	11146001
YY1	Activation	8753872

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001974	Process	Blood vessel remodeling	IEA
GO:0001975	Process	Response to amphetamine	IEA
GO:0002443	Process	Leukocyte mediated immunity	IEA
GO:0003824	Function	Catalytic activity	TAS	3443096
GO:0004500	Function	Dopamine beta-monooxygenase activity	IBA	21873635
GO:0004500	Function	Dopamine beta-monooxygenase activity	IDA	3443096, 7961964
GO:0005507	Function	Copper ion binding	IBA	21873635
GO:0005507	Function	Copper ion binding	IDA	7961964, 27152332
GO:0005515	Function	Protein binding	IPI	32296183, 32814053
GO:0005576	Component	Extracellular region	NAS	14718574
GO:0005615	Component	Extracellular space	IBA	21873635
GO:0005615	Component	Extracellular space	IDA	7961964
GO:0005737	Component	Cytoplasm	TAS	3443096
GO:0005783	Component	Endoplasmic reticulum	IDA
GO:0006589	Process	Octopamine biosynthetic process	IBA	21873635
GO:0007268	Process	Chemical synaptic transmission	TAS	2880016
GO:0007613	Process	Memory	IEA
GO:0007626	Process	Locomotory behavior	IEA
GO:0008542	Process	Visual learning	IEA
GO:0016020	Component	Membrane	TAS	3443096
GO:0016021	Component	Integral component of membrane	IEA
GO:0030658	Component	Transport vesicle membrane	IEA
GO:0030667	Component	Secretory granule membrane	IBA	21873635
GO:0030667	Component	Secretory granule membrane	IDA	7961964
GO:0031418	Function	L-ascorbic acid binding	IEA
GO:0034451	Component	Centriolar satellite	IDA
GO:0034466	Component	Chromaffin granule lumen	IEA
GO:0034774	Component	Secretory granule lumen	IDA	7961964
GO:0034774	Component	Secretory granule lumen	TAS
GO:0042127	Process	Regulation of cell population proliferation	IEA
GO:0042309	Process	Homoiothermy	IEA
GO:0042420	Process	Dopamine catabolic process	IBA	21873635
GO:0042420	Process	Dopamine catabolic process	IDA	3443096, 7961964
GO:0042421	Process	Norepinephrine biosynthetic process	IBA	21873635
GO:0042421	Process	Norepinephrine biosynthetic process	IEA
GO:0042421	Process	Norepinephrine biosynthetic process	IMP	27148966
GO:0042423	Process	Catecholamine biosynthetic process	TAS
GO:0042584	Component	Chromaffin granule membrane	IEA
GO:0042593	Process	Glucose homeostasis	IEA
GO:0042596	Process	Fear response	IEA
GO:0042711	Process	Maternal behavior	IEA
GO:0043231	Component	Intracellular membrane-bounded organelle	IDA
GO:0045202	Component	Synapse	IEA
GO:0045907	Process	Positive regulation of vasoconstriction	IEA
GO:0048149	Process	Behavioral response to ethanol	IEA
GO:0048265	Process	Response to pain	IEA
GO:0050900	Process	Leukocyte migration	IEA
GO:0120162	Process	Positive regulation of cold-induced thermogenesis	ISS	9139828
GO:2001236	Process	Regulation of extrinsic apoptotic signaling pathway	IEA

Other IDs

• MIM: 609312
• HGNC: 2689
• e!Ensembl: ENSG00000123454

Protein

• UniProt ID: P09172
• Protein name: Dopamine beta-hydroxylase (EC 1.14.17.1) (Dopamine beta-monooxygenase) [Cleaved into: Soluble dopamine beta-hydroxylase]
• Protein function: Catalyzes the hydroxylation of dopamine to noradrenaline (also known as norepinephrine), and is thus vital for regulation of these neurotransmitters. {ECO:0000269|PubMed:27148966, ECO:0000269|PubMed:3443096, ECO:0000269|PubMed:7961964, ECO:00002
• PDB: 4ZEL
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF03351	DOMON	55 → 172	DOMON domain	Domain
  PF01082	Cu2_monooxygen	214 → 341	Copper type II ascorbate-dependent monooxygenase, N-terminal domain	Domain
  PF03712	Cu2_monoox_C	360 → 516	Copper type II ascorbate-dependent monooxygenase, C-terminal domain	Domain

• Sequence:

  MPALSRWASLPGPSMREAAFMYSTAVAIFLVILVAALQGSAPRESPLPYHIPLDPEGSLE
  LSWNVSYTQEAIHFQLLVRRLKAGVLFGMSDRGELENADLVVLWTDGDTAYFADAWSDQK
  GQIHLDPQQDYQLLQVQRTPEGLTLLFKRPFGTCDPKDYLIEDGTVHLVYGILEEPFRSL
  EAINGSGLQMGLQRVQLLKPNIPEPELPSDACTMEVQAPNIQIPSQETTYWCYIKELPKG
  FSRHHIIKYEPIVTKGNEALVHHMEVFQCAPEMDSVPHFSGPCDSKMKPDRLNYCRHVLA
  AWALGAKAFYYPEEAGLAFGGPGSSRYLRLEVHYHNPLVIEGRNDSSGIRLYYTAKLRRF
  NAGIMELGLVYTPVMAIPPRETAFILTGYCTDKCTQLALPPSGIHIFASQLHTHLTGRKV
  VTVLVRDGREWEIVNQDNHYSPHFQEIRMLKKVVSVHPGDVLITSCTYNTEDRELATVGG
  FGILEEMCVNYVHYYPQTQLELCKSAVDAGFLQKYFHLINRFNNEDVCTCPQASVSQQFT
  SVPWNSFNRDVLKALYSFAPISMHCNKSSAVRFQGEWNLQPLPKVISTLEEPTPQCPTSQ
  GRSPAGPTVVSIGGGKG

• Sequence length: 617

Pathways

KEGG:

Tyrosine metabolism
Metabolic pathways

Reactome:

Catecholamine biosynthesis

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Anemia	Anemia	rs118204044, rs118204045, rs118204046, rs121918330, rs869320719, rs869312029, rs121918332, rs869320724, rs767094129, rs786205058, rs786205059, rs137853119, rs137853120, rs137853121, rs1384933966, rs137853122, rs137853123, rs786205060, rs267607121, rs121908584, rs80338697, rs80338699, rs120074166, rs120074167, rs1050828, rs74575103, rs137852314, rs5030868, rs137852316, rs137852317, rs137852318, rs137852319, rs137852320, rs137852321, rs137852322, rs137852323, rs137852324, rs72554665, rs387906468, rs5030872, rs137852326, rs137852333, rs137852327, rs137852328, rs137852329, rs137852330, rs137852331, rs137852332, rs137852334, rs137852335, rs137852336, rs137852339, rs76645461, rs137852340, rs137852341, rs78478128, rs137852343, rs137852344, rs137852345, rs587776730, rs137852346, rs137852347, rs137852349, rs2070404412, rs2070350038, rs2070350009, rs137852303, rs137852304, rs33946267, rs34378160, rs33933298, rs11549407, rs35724775, rs34598529, rs41469945, rs267607201, rs80338694, rs80338696, rs387907018, rs398123546, rs78365220, rs587777100, rs587777101, rs483352840, rs869312752, rs765487627, rs1557229599, rs1557230040, rs1555524842, rs782090947, rs1358275550, rs1557229736, rs1557230573, rs1556323334, rs1233124208, rs1293528130, rs146864395, rs1595503440, rs1603411214, rs137852325, rs1575247302, rs1603411177, rs1336651679, rs782322505
Hyperinsulinism	Hyperinsulinism	rs387906407, rs151344623, rs121913156, rs137853245, rs80356655, rs104894010, rs104894012, rs104894014, rs104894015, rs137852676, rs587783169, rs72559716, rs541269678, rs151344624, rs797045209, rs761749884, rs797045624, rs863225280, rs139964066, rs1057516281, rs1057516317, rs576684889, rs201682634, rs1350717554, rs768951263, rs1260178539, rs200670692, rs72559734, rs1400535021, rs372307320, rs1554923999, rs751279984, rs1008906426, rs367850779, rs1382448285, rs1564977373, rs750586210, rs1599937180
Lung carcinoma	Squamous cell carcinoma of lung	rs1805076, rs121909071, rs121913530, rs112445441, rs121913529, rs121913535, rs121913297, rs121913279, rs104886003, rs397516975, rs11554290, rs121913364, rs121913351, rs121913369, rs121913355, rs121912470, rs121913273, rs121913281, rs121913348, rs727503093, rs121913353, rs397516890, rs397516896, rs121913378, rs397516897, rs397516977, rs397516978, rs397516979, rs397516980, rs397516981, rs397516982, rs121913240, rs17851045, rs397517086, rs121913428, rs397517094, rs397517098, rs397517106, rs121913465, rs397517108, rs397517111, rs397517112, rs397517114, rs397517116, rs1554350366, rs397517127, rs397517200, rs397517202, rs121913283, rs121913370, rs121913357, rs727503106, rs121913238, rs727503108, rs397517040, rs397516976, rs1555618025, rs1057519729, rs1584238193	28604730
Neuroblastoma	Neuroblastoma	rs121908161, rs113994087, rs113994089, rs281864719, rs863225285, rs863225284, rs863225283, rs281864720, rs863225282, rs863225281, rs1057519698, rs915983602, rs1469271544	25174395
Orthostatic hypotension	ORTHOSTATIC HYPOTENSION 1	rs74853476, rs772361572, rs1437737028, rs768149947	27778639, 14598346, 21209083, 21471955, 15060114, 27830117, 11857564, 27604308
Pheochromocytoma	Pheochromocytoma	rs121908826, rs121908830, rs121908821, rs5030821, rs5030820, rs104893826, rs5030808, rs587776644, rs80338844, rs104894306, rs104894309, rs75076352, rs75996173, rs77709286, rs74799832, rs387906651, rs121908813, rs121908822, rs121908814, rs121908825, rs121908827, rs121908829, rs121908831, rs121908815, rs587781773, rs786203251, rs786202100, rs864321636, rs864321638, rs864321639, rs864321643, rs864321641, rs864321642, rs864321640, rs864321644, rs876659130, rs876658477, rs878854594, rs886039439, rs886041237, rs121908816, rs1131691061, rs760169139, rs780133289, rs1558752379	22569243

Unknown
Disease name	Disease term	dbSNP ID	References
Bipolar disorder	Bipolar Disorder		23384717, 8840392, 8750358, 10578238, 7719704
Cardiovascular diseases	Cardiovascular Diseases		30595370
Dopamine beta hydroxylase deficiency	dopamine beta hydroxylase deficiency, Dopamine beta-hydroxylase deficiency
Dyssomnia	Dyssomnias
Extra-adrenal pheochromocytoma	Pheochromocytoma, Extra-Adrenal		22569243
High palate	Byzanthine arch palate
Hypoglycemia	Hypoglycemia, Neonatal hypoglycemia
Liver carcinoma	Liver carcinoma		28284560
Mental depression	Mental Depression, Depressive disorder, Unipolar Depression, Major Depressive Disorder	rs587778876, rs587778877	23906995, 23305027, 17698206, 20621148, 23512949, 23906995, 23305027, 23512949, 18982239, 20621148, 24888991, 11904130, 11904129, 11904130, 11904129, 24888991
Mood disorder	Mood Disorders		7811839, 6846043, 12942993, 18982239
Nocturia	Nocturia
Orthostatic syncope	Orthostatic syncope
Paranoia	Paranoia		10673769, 17157269, 12555232
Ptosis	Blepharoptosis, Ptosis	rs139920573
Rhinitis	Rhinitis
Sleep disorders	Sleep Disorders