DBH

dopamine beta-hydroxylase

Basic information

Region (hg38): 9:133636363-133659329

Links

ENSG00000123454 ∙ NCBI:1621 ∙ OMIM:609312 ∙ HGNC:2689 ∙ Uniprot:P09172 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• orthostatic hypotension 1 (Moderate), mode of inheritance: AR
• orthostatic hypotension 1 (Supportive), mode of inheritance: AR
• orthostatic hypotension 1 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Orthostatic hypotension 1	AR	Biochemical; Renal	Medical therapy (eg, droxidopa) can effectively treat manifestations such as orthostatic hypotension; Surveillance of renal function should be instituted; For untreated individuals, circumstances such as vigorous exercise, hot environements, and dehydration should be avoided; In infantile-onset disease, awareness of hypotension, hypothermia, and hypoglycemia may be beneficial	Biochemical; Genitourinary; Neurologic; Ophthalmologic; Renal	3010116; 2890806; 2880016; 2300263; 2217667; 9651662; 16722595; 1677640; 11857564; 20063034; 20301647; 21471955

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DBH gene.

• Orthostatic hypotension 1 (7 variants)
• not provided (1 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DBH gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			8	80	8	96
missense			160	12	8	180
nonsense	3		1			4
start loss						0
frameshift	4		1			5
inframe indel			3			3
splice donor/acceptor (+/-2bp)	1					1
splice region			13	12	5	30
non coding			34	42	45	121
Total	8	0	207	134	61

Highest pathogenic variant AF is 0.00104

Variants in DBH

This is a list of pathogenic ClinVar variants found in the DBH region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
9-133636378-G-T		Inborn genetic diseases	Uncertain significance (Dec 21, 2022)
9-133636381-C-T		Orthostatic hypotension 1	Uncertain significance (Oct 04, 2022)
9-133636387-C-A		Orthostatic hypotension 1	Uncertain significance (Dec 11, 2023)
9-133636388-G-A		Orthostatic hypotension 1 • Inborn genetic diseases	Uncertain significance (Jun 13, 2022)
9-133636397-G-A		Orthostatic hypotension 1	Uncertain significance (Aug 14, 2021)
9-133636404-C-T		Orthostatic hypotension 1	Likely benign (Dec 19, 2022)
9-133636418-G-A		Orthostatic hypotension 1	Uncertain significance (Feb 19, 2022)
9-133636432-A-G		Orthostatic hypotension 1	Uncertain significance (Jan 13, 2018)
9-133636433-T-C		Orthostatic hypotension 1	Uncertain significance (Sep 25, 2021)
9-133636433-T-G		Orthostatic hypotension 1	Uncertain significance (Nov 26, 2022)
9-133636447-G-A		Orthostatic hypotension 1	Benign (Aug 01, 2024)
9-133636458-C-T		Orthostatic hypotension 1	Likely benign (May 31, 2022)
9-133636459-C-T			Likely benign (Nov 17, 2017)
9-133636476-C-T		Orthostatic hypotension 1	Benign/Likely benign (Jan 20, 2024)
9-133636477-G-A		Orthostatic hypotension 1	Uncertain significance (Sep 27, 2022)
9-133636491-G-A		Orthostatic hypotension 1	Likely benign (Oct 03, 2023)
9-133636499-G-A		Orthostatic hypotension 1 • Inborn genetic diseases	Uncertain significance (Oct 02, 2023)
9-133636517-A-G		Orthostatic hypotension 1	Uncertain significance (Jul 07, 2023)
9-133636517-A-T		Inborn genetic diseases	Uncertain significance (Aug 12, 2021)
9-133636524-C-G		Orthostatic hypotension 1	Uncertain significance (Jan 12, 2018)
9-133636536-G-A		Orthostatic hypotension 1	Conflicting classifications of pathogenicity (Dec 17, 2023)
9-133636554-C-T		Orthostatic hypotension 1	Likely benign (Sep 20, 2023)
9-133636575-C-A		Orthostatic hypotension 1	Likely benign (Oct 17, 2023)
9-133636580-A-G		Orthostatic hypotension 1	Likely benign (Dec 11, 2023)
9-133636588-C-T		Orthostatic hypotension 1	Uncertain significance (Nov 08, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DBH	protein_coding	protein_coding	ENST00000393056	12	22985

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.34e-10	0.750	125529	0	219	125748	0.000871

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.13	439	377	1.16	0.0000255	3998
Missense in Polyphen		165	144.83	1.1393		1529
Synonymous	-0.816	180	167	1.08	0.0000127	1245
Loss of Function	1.54	19	27.8	0.685	0.00000132	313

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00160	0.00159
Ashkenazi Jewish	0.00	0.00
East Asian	0.000601	0.000598
Finnish	0.000371	0.000231
European (Non-Finnish)	0.00135	0.00131
Middle Eastern	0.000601	0.000598
South Asian	0.000196	0.000196
Other	0.00166	0.00163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Conversion of dopamine to noradrenaline. {ECO:0000269|PubMed:27148966, ECO:0000269|PubMed:3443096, ECO:0000269|PubMed:7961964, ECO:0000269|PubMed:8546710}.
• Disease: DISEASE: Dopamine beta-hydroxylase deficiency (DBH deficiency) [MIM:223360]: Characterized by profound deficits in autonomic and cardiovascular function, but apparently only subtle signs, if any, of central nervous system dysfunction. {ECO:0000269|PubMed:11857564}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Tyrosine metabolism - Homo sapiens (human);Sympathetic Nerve Pathway (Neuroeffector Junction);Tyrosine hydroxylase deficiency;Tyrosinemia, transient, of the newborn;Dopamine beta-hydroxylase deficiency;Disulfiram Action Pathway;Tyrosine Metabolism;Alkaptonuria;Monoamine oxidase-a deficiency (MAO-A);Hawkinsinuria;Tyrosinemia Type I;Catecholamine Biosynthesis;Aromatic L-Aminoacid Decarboxylase Deficiency;Amino Acid metabolism;Neurotransmitter Disorders;Biogenic Amine Synthesis;Monoamine Transport;Metabolism of amino acids and derivatives;Metabolism;catecholamine biosynthesis;Pyrimidine metabolism;Catecholamine biosynthesis;Tyrosine metabolism;Amine-derived hormones (Consensus)

Recessive Scores

• pRec: 0.695

Intolerance Scores

• loftool: 0.802
• rvis_EVS: -0.01
• rvis_percentile_EVS: 52.38

Haploinsufficiency Scores

• pHI: 0.238
• hipred: N
• hipred_score: 0.390
• ghis: 0.440

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.870

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Dbh
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; skeleton phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: dbh
• Affected structure: sleep
• Phenotype tag: abnormal
• Phenotype quality: increased occurrence

Gene ontology

• Biological process: cytokine production;blood vessel remodeling;response to amphetamine;leukocyte mediated immunity;octopamine biosynthetic process;chemical synaptic transmission;memory;locomotory behavior;visual learning;regulation of cell population proliferation;homoiothermy;dopamine catabolic process;norepinephrine biosynthetic process;catecholamine biosynthetic process;glucose homeostasis;fear response;maternal behavior;positive regulation of vasoconstriction;behavioral response to ethanol;response to pain;leukocyte migration;oxidation-reduction process;positive regulation of cold-induced thermogenesis;regulation of extrinsic apoptotic signaling pathway
• Cellular component: extracellular region;extracellular space;cytoplasm;endoplasmic reticulum;microtubule organizing center;membrane;integral component of membrane;transport vesicle membrane;secretory granule membrane;chromaffin granule lumen;secretory granule lumen;chromaffin granule membrane;intracellular membrane-bounded organelle
• Molecular function: catalytic activity;dopamine beta-monooxygenase activity;copper ion binding;oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced ascorbate as one donor, and incorporation of one atom of oxygen;L-ascorbic acid binding