HDC
protein-codinghistidine decarboxylase
Gene summary
This gene encodes a member of the group II decarboxylase family and forms a homodimer that converts L-histidine to histamine in a pyridoxal phosphate dependent manner. Histamine regulates several physiologic processes, including neurotransmission, gastric acid secretion,inflamation, and smooth muscle tone.[provided by RefSeq, Aug 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~24.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0007661
Submitter: Ambry Genetics
Inheritance Pattern: Unknown
Disease ID:MONDO:0007661
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Neurologic
Intervention: General
Rationale: 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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to HDC variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002112.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 9 | 1 | 11 | ||
| missense | 72 | 5 | 1 | 78 | ||
| nonsense | 1 | 2 | 3 | |||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | 1 | 3 | ||
| Total | 2 | 1 | 77 | 14 | 2 | 96 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002103.2 | 12 | MANE Select | |
| Ensembl | ENSP00000267845.3 | 12 | MANE Select | |
| RefSeq | NP_001293075.1 | 11 | Standard | |
| Ensembl | ENSP00000440252.1 | 11 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| hdc | Danio rerio | Structure: brain Quality: morphology abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Histidine metabolism - Homo sapiens (human)
- Histidine Metabolism
- Histidinemia
- Amino Acid metabolism
- Biogenic Amine Synthesis
Biological Process
- histamine biosynthetic process
- histidine metabolic process
- histidine catabolic process
- catecholamine biosynthetic process
Molecular Function
- histidine decarboxylase activity
- protein binding
- pyridoxal phosphate binding
Cellular Component
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000267845
- Coding exons
- 12
- Length
- 24080
- Individuals with no LoFs
- 125729
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 19
- Defined
- 125748
- p
- 0.0000756
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.04 | 312 | 368 | 0.848 | 0.0000216 | 4359 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00017 | 0.00017 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000088 | 0.000088 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalyzes the biosynthesis of histamine from histidine. {ECO:0000269|PubMed:22767596}.;
Recessive Scores
- pRec
- 0.256
Intolerance Scores
- LoFtool
- 0.409
- RVIS EVS
- -0.24
- RVIS percentile EVS
- 36.17
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.960
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |