HRH4
protein-codinghistamine receptor H4, the group of Histamine receptors
Gene summary
Histamine is a ubiquitous messenger molecule released from mast cells, enterochromaffin-like cells, and neurons. Its various actions are mediated by a family of histamine receptors, which are a subset of the G-protein coupled receptor superfamily. This gene encodes a histamine receptor that is predominantly expressed in haematopoietic cells. The protein is thought to play a role in inflammation and allergy reponses. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~19.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to HRH4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_021624.4. 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 | 0 | |||||
| missense | 54 | 5 | 59 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 54 | 5 | 0 | 59 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_067637.2 | 3 | MANE Select | |
| Ensembl | ENSP00000256906.4 | 3 | MANE Select | |
| RefSeq | NP_001137300.1 | 2 | Standard | |
| RefSeq | NP_001153638.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Neuroactive ligand-receptor interaction - Homo sapiens (human)
- GPCRs, Other
- Signaling by GPCR
- Signal Transduction
- Histamine receptors
Biological Process
- inflammatory response
- G protein-coupled receptor signaling pathway
- G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
- adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway
- positive regulation of cytosolic calcium ion concentration
Molecular Function
- G protein-coupled receptor activity
- histamine receptor activity
- G protein-coupled serotonin receptor activity
- G protein-coupled acetylcholine receptor activity
- neurotransmitter receptor activity
Cellular Component
- plasma membrane
- integral component of plasma membrane
- dendrite
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000256906
- Coding exons
- 3
- Length
- 19329
- Individuals with no LoFs
- 125579
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 163
- Defined
- 125742
- p
- 0.000648
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.468 | 180 | 199 | 0.907 | 0.0000100 | 2522 |
| Missense (PolyPhen) | 53 | 53.938 | 0.98262 | 727 | ||
| Synonymous | -1.44 | 90 | 74.2 | 1.21 | 0.00000381 | 784 |
| Loss of Function | 0.375 | 12 | 13.5 | 0.890 | 7.09e-7 | 171 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00086 | 0.00086 | rare |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0.00040 | 0.00040 | rare |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00035 | 0.00034 | rare |
| South Asian | 0.0032 | 0.0032 | notable |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: The H4 subclass of histamine receptors could mediate the histamine signals in peripheral tissues. Displays a significant level of constitutive activity (spontaneous activity in the absence of agonist). {ECO:0000269|PubMed:12503632}.;
Recessive Scores
- pRec
- 0.122
Intolerance Scores
- LoFtool
- 0.884
- RVIS EVS
- 0.68
- RVIS percentile EVS
- 85.04
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0747
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |