DDC

dopa decarboxylase

Basic information

Region (hg38): 7:50458436-50565405

Links

ENSG00000132437 ∙ NCBI:1644 ∙ OMIM:107930 ∙ HGNC:2719 ∙ Uniprot:P20711 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• aromatic L-amino acid decarboxylase deficiency (Definitive), mode of inheritance: AR
• aromatic L-amino acid decarboxylase deficiency (Definitive), mode of inheritance: AR
• aromatic L-amino acid decarboxylase deficiency (Strong), mode of inheritance: AR
• aromatic L-amino acid decarboxylase deficiency (Supportive), mode of inheritance: AR
• aromatic L-amino acid decarboxylase deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Aromatic l-amino acid decarboxylase deficiency	AR	Biochemical	Medical treatment (eg, with MAOI, dopamine agonists, and pyridoxine) has been reported as resulting in clinical improvement in some patients, largely with a milder form of disease, though functional clinical outcomes may be poor in many individuals	Biochemical; Neurologic	1700191; 1357595; 9309516; 12891654; 15079002; 20505134; 21963339; 30952622; 31104889

ClinVar

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

• Deficiency of aromatic-L-amino-acid decarboxylase (30 variants)
• Inborn genetic diseases (2 variants)
• RASopathy (1 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DDC 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			4	111	1	116
missense	9	15	172	6	2	204
nonsense	11	1	1			13
start loss						0
frameshift	8	3				11
inframe indel			2			2
splice donor/acceptor (+/-2bp)		10				10
splice region	2	1	15	25	1	44
non coding			10	76	43	129
Total	28	29	189	193	46

Highest pathogenic variant AF is 0.0000591

Variants in DDC

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

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

Position	Type	Phenotype	Significance	ClinVar
7-50458521-G-A		Deficiency of aromatic-L-amino-acid decarboxylase	Benign (Jan 12, 2018)
7-50458548-A-G		Deficiency of aromatic-L-amino-acid decarboxylase	Benign (Jan 12, 2018)
7-50458565-A-G		Deficiency of aromatic-L-amino-acid decarboxylase	Benign (Jan 13, 2018)
7-50458588-C-T		Deficiency of aromatic-L-amino-acid decarboxylase	Uncertain significance (Jan 13, 2018)
7-50458707-G-A		Deficiency of aromatic-L-amino-acid decarboxylase	Uncertain significance (Jan 13, 2018)
7-50458746-A-C		Deficiency of aromatic-L-amino-acid decarboxylase	Uncertain significance (Jun 14, 2016)
7-50458749-G-A		Deficiency of aromatic-L-amino-acid decarboxylase	Uncertain significance (Jan 12, 2018)
7-50458826-C-G		Deficiency of aromatic-L-amino-acid decarboxylase	Uncertain significance (Jan 12, 2018)
7-50458839-G-T		Deficiency of aromatic-L-amino-acid decarboxylase	Likely benign (Jan 13, 2018)
7-50462937-T-G			Benign (May 07, 2021)
7-50463064-G-A			Benign (Mar 26, 2021)
7-50463171-G-A			Benign (Apr 12, 2021)
7-50463237-C-A		Deficiency of aromatic-L-amino-acid decarboxylase	Uncertain significance (Dec 27, 2020)
7-50463238-C-T		Deficiency of aromatic-L-amino-acid decarboxylase	Uncertain significance (Jul 04, 2022)
7-50463239-T-C		Global developmental delay • Inborn genetic diseases • Deficiency of aromatic-L-amino-acid decarboxylase • DDC-related disorder	Likely benign (Jan 19, 2024)
7-50463247-C-T		Deficiency of aromatic-L-amino-acid decarboxylase	Uncertain significance (Jul 11, 2022)
7-50463248-G-A		Deficiency of aromatic-L-amino-acid decarboxylase	Uncertain significance (Oct 13, 2022)
7-50463253-A-C		Deficiency of aromatic-L-amino-acid decarboxylase	Uncertain significance (Dec 03, 2021)
7-50463254-C-T		Deficiency of aromatic-L-amino-acid decarboxylase	Uncertain significance (Jul 18, 2022)
7-50463255-G-A		Deficiency of aromatic-L-amino-acid decarboxylase	Likely benign (Aug 31, 2022)
7-50463257-C-T		Deficiency of aromatic-L-amino-acid decarboxylase	Uncertain significance (Jan 22, 2024)
7-50463258-G-A		Deficiency of aromatic-L-amino-acid decarboxylase	Likely benign (Apr 13, 2023)
7-50463261-C-A		Deficiency of aromatic-L-amino-acid decarboxylase	Likely benign (Dec 06, 2022)
7-50463261-C-T		Deficiency of aromatic-L-amino-acid decarboxylase	Likely benign (Apr 18, 2021)
7-50463262-G-A		Deficiency of aromatic-L-amino-acid decarboxylase	Uncertain significance (Oct 03, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DDC	protein_coding	protein_coding	ENST00000444124	13	107021

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.75e-8	0.940	125684	0	64	125748	0.000255

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.409	258	277	0.931	0.0000180	3133
Missense in Polyphen		115	126.09	0.91202		1402
Synonymous	-0.719	120	110	1.09	0.00000778	947
Loss of Function	1.90	16	26.5	0.603	0.00000133	315

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000868	0.0000868
Ashkenazi Jewish	0.00179	0.00179
East Asian	0.000272	0.000272
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000247	0.000246
Middle Eastern	0.000272	0.000272
South Asian	0.000196	0.000196
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the decarboxylation of L-3,4- dihydroxyphenylalanine (DOPA) to dopamine, L-5-hydroxytryptophan to serotonin and L-tryptophan to tryptamine.
• Disease: DISEASE: Aromatic L-amino-acid decarboxylase deficiency (AADCD) [MIM:608643]: An inborn error in neurotransmitter metabolism that leads to combined serotonin and catecholamine deficiency. It causes developmental and psychomotor delay, poor feeding, lethargy, ptosis, intermittent hypothermia, gastrointestinal disturbances. The onset is early in infancy and inheritance is autosomal recessive. {ECO:0000269|PubMed:14991824, ECO:0000269|PubMed:15079002, ECO:0000269|Ref.12}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Tryptophan metabolism - Homo sapiens (human);Serotonergic synapse - Homo sapiens (human);Dopaminergic synapse - Homo sapiens (human);Phenylalanine metabolism - Homo sapiens (human);Amphetamine addiction - Homo sapiens (human);Tyrosine metabolism - Homo sapiens (human);Alcoholism - Homo sapiens (human);Cocaine addiction - Homo sapiens (human);Nicotine Pathway (Dopaminergic Neuron), Pharmacodynamics;Selective Serotonin Reuptake Inhibitor Pathway, Pharmacodynamics;Sympathetic Nerve Pathway (Pre- and Post- Ganglionic 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;Tryptophan Metabolism;Aromatic L-Aminoacid Decarboxylase Deficiency;Nicotine Activity on Dopaminergic Neurons;Parkinsons Disease Pathway;Dopamine metabolism;Dopaminergic Neurogenesis;Amino Acid metabolism;Tryptophan metabolism;Biogenic Amine Synthesis;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;serotonin and melatonin biosynthesis;Metabolism of amino acids and derivatives;Metabolism;Phenylalanine degradation;catecholamine biosynthesis;AndrogenReceptor;tryptophan degradation via tryptamine;Catecholamine biosynthesis;Tryptophan degradation;superpathway of tryptophan utilization;Tyrosine metabolism;Serotonin and melatonin biosynthesis;Amine-derived hormones (Consensus)

Recessive Scores

• pRec: 0.410

Intolerance Scores

• loftool: 0.794
• rvis_EVS: 0.38
• rvis_percentile_EVS: 75.51

Haploinsufficiency Scores

• pHI: 0.548
• hipred: N
• hipred_score: 0.391
• ghis: 0.407

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.445

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ddc
• Phenotype: renal/urinary system phenotype; immune system phenotype; vision/eye phenotype; 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); reproductive system 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); 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; cellular phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: ddc
• Affected structure: dopaminergic neuron
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: cellular amino acid metabolic process;circadian rhythm;multicellular organism aging;aminergic neurotransmitter loading into synaptic vesicle;isoquinoline alkaloid metabolic process;cellular response to drug;dopamine biosynthetic process;catecholamine biosynthetic process;serotonin biosynthetic process;indolalkylamine biosynthetic process;response to pyrethroid;phytoalexin metabolic process;cellular response to alkaloid;cellular response to growth factor stimulus
• Cellular component: cytosol;synaptic vesicle;axon;neuronal cell body;extracellular exosome
• Molecular function: aromatic-L-amino-acid decarboxylase activity;protein binding;amino acid binding;enzyme binding;protein domain specific binding;pyridoxal phosphate binding;L-dopa decarboxylase activity