HDC

histidine decarboxylase

Basic information

Region (hg38): 15:50241946-50265965

Links

ENSG00000140287 ∙ NCBI:3067 ∙ OMIM:142704 ∙ HGNC:4855 ∙ Uniprot:P19113 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Tourette syndrome (Limited), mode of inheritance: Unknown
• Tourette syndrome (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Tourette's syndrome	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	20445167

ClinVar

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

• Inborn genetic diseases (22 variants)
• not provided (7 variants)
• Tourette syndrome (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HDC 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				2	1	3
missense			23	2	2	27
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding						0
Total	0	0	23	4	3

Variants in HDC

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

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

Position	Type	Phenotype	Significance	ClinVar
15-50242303-C-T		not specified	Uncertain significance (Jan 18, 2022)
15-50242474-A-G		not specified	Uncertain significance (Dec 14, 2021)
15-50242478-G-A		not specified	Uncertain significance (Nov 22, 2021)
15-50242506-C-T			Benign (Dec 31, 2019)
15-50242520-T-A		not specified	Uncertain significance (Dec 21, 2021)
15-50242574-C-T		not specified	Uncertain significance (Apr 06, 2022)
15-50242592-A-G			Benign (Dec 31, 2019)
15-50242635-A-G		HDC-related disorder	Benign (Oct 28, 2019)
15-50242666-C-T		not specified	Uncertain significance (Mar 29, 2023)
15-50242681-A-T		Tourette syndrome	Uncertain significance (Sep 28, 2020)
15-50242693-G-C		not specified	Uncertain significance (Mar 14, 2023)
15-50242694-C-A		not specified	Uncertain significance (Jun 21, 2023)
15-50242725-A-G		HDC-related disorder	Likely benign (May 02, 2019)
15-50242738-G-A		not specified	Likely benign (Feb 05, 2024)
15-50242738-G-T		Tourette syndrome	Uncertain significance (Jan 09, 2018)
15-50242769-T-C			Benign/Likely benign (Mar 01, 2022)
15-50242793-G-A		not specified	Uncertain significance (Apr 06, 2023)
15-50242811-T-C		not specified	Uncertain significance (Dec 14, 2021)
15-50243151-G-A		not specified	Uncertain significance (Sep 17, 2021)
15-50248252-A-C		Tourette syndrome	Uncertain significance (Mar 25, 2024)
15-50248307-C-G		not specified	Uncertain significance (Jan 10, 2023)
15-50252520-C-T		Tourette syndrome	Pathogenic (Jan 08, 2014)
15-50252673-C-T		not specified	Uncertain significance (Feb 21, 2024)
15-50252712-G-T		not specified	Uncertain significance (Mar 14, 2023)
15-50252749-G-A			Likely benign (Aug 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HDC	protein_coding	protein_coding	ENST00000267845	12	24080

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00411	0.996	125729	0	19	125748	0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.04	312	368	0.848	0.0000216	4359
Missense in Polyphen		100	158.66	0.63026		1907
Synonymous	-0.849	157	144	1.09	0.00000866	1318
Loss of Function	3.49	10	31.0	0.323	0.00000189	333

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000173	0.000173
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000881	0.0000879
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the biosynthesis of histamine from histidine. {ECO:0000269|PubMed:22767596}.
• Pathway: Histidine metabolism - Homo sapiens (human);Histidine Metabolism;Histidinemia;Amino Acid metabolism;Biogenic Amine Synthesis;Histidine catabolism;Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism;Metabolism of amino acids and derivatives;Metabolism;histamine biosynthesis;Histidine degradation (Consensus)

Recessive Scores

• pRec: 0.256

Intolerance Scores

• loftool: 0.409
• rvis_EVS: -0.24
• rvis_percentile_EVS: 36.17

Haploinsufficiency Scores

• pHI: 0.191
• hipred: Y
• hipred_score: 0.554
• ghis: 0.400

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.960

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hdc
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system 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); homeostasis/metabolism phenotype; immune system phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); 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); growth/size/body region phenotype

Zebrafish Information Network

• Gene name: hdc
• Affected structure: brain
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: histamine biosynthetic process;histidine metabolic process;histidine catabolic process;catecholamine biosynthetic process
• Cellular component: cytosol
• Molecular function: histidine decarboxylase activity;protein binding;pyridoxal phosphate binding