HRH4

histamine receptor H4, the group of Histamine receptors

Basic information

Region (hg38): 18:24460636-24479961

Links

ENSG00000134489 ∙ NCBI:59340 ∙ OMIM:606792 ∙ HGNC:17383 ∙ Uniprot:Q9H3N8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HRH4 gene.

• Inborn genetic diseases (14 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HRH4 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						0
missense			12	2		14
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	12	2	0

Variants in HRH4

This is a list of pathogenic ClinVar variants found in the HRH4 region.

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

Position	Type	Phenotype	Significance	ClinVar
18-24460771-C-T		not specified	Uncertain significance (May 15, 2023)
18-24460858-A-G		not specified	Uncertain significance (Jan 24, 2024)
18-24468820-A-G		not specified	Uncertain significance (Nov 07, 2022)
18-24468821-C-G		not specified	Uncertain significance (Oct 17, 2023)
18-24468821-C-T		not specified	Likely benign (May 11, 2022)
18-24468919-A-G		not specified	Uncertain significance (Apr 17, 2023)
18-24468943-T-A		not specified	Uncertain significance (Feb 17, 2022)
18-24476764-A-C		not specified	Uncertain significance (Jan 09, 2024)
18-24476816-G-A		not specified	Uncertain significance (Sep 16, 2021)
18-24476844-T-G		not specified	Uncertain significance (Jul 13, 2021)
18-24476870-G-A		not specified	Uncertain significance (Jan 03, 2024)
18-24476956-A-T		not specified	Uncertain significance (Oct 05, 2022)
18-24477041-G-T		not specified	Likely benign (Mar 24, 2023)
18-24477216-T-G		not specified	Uncertain significance (May 08, 2023)
18-24477323-T-G		not specified	Uncertain significance (Jul 05, 2023)
18-24477414-T-C		not specified	Uncertain significance (May 26, 2022)
18-24477453-C-T		not specified	Uncertain significance (Sep 16, 2021)
18-24477459-T-G		not specified	Uncertain significance (Jan 31, 2024)
18-24477491-G-A		not specified	Uncertain significance (Aug 08, 2023)
18-24477510-G-T		not specified	Uncertain significance (Feb 23, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HRH4	protein_coding	protein_coding	ENST00000256906	3	19329

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.22e-8	0.236	125579	0	163	125742	0.000648

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.468	180	199	0.907	0.0000100	2522
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000948	0.000948
Ashkenazi Jewish	0.000397	0.000397
East Asian	0.000217	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.000348	0.000343
Middle Eastern	0.000217	0.000217
South Asian	0.00317	0.00317
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: Neuroactive ligand-receptor interaction - Homo sapiens (human);GPCRs, Other;Signaling by GPCR;Signal Transduction;Histamine receptors;Amine ligand-binding receptors;Class A/1 (Rhodopsin-like receptors);GPCR ligand binding;G alpha (i) signalling events;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.122

Intolerance Scores

• loftool: 0.884
• rvis_EVS: 0.68
• rvis_percentile_EVS: 85.04

Haploinsufficiency Scores

• pHI: 0.145
• hipred: N
• hipred_score: 0.146

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0747

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hrh4
• Phenotype: immune system phenotype; hematopoietic system phenotype; homeostasis/metabolism phenotype

Gene ontology

• 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;chemical synaptic transmission;biological_process;regulation of MAPK cascade;G protein-coupled serotonin receptor signaling pathway
• Cellular component: plasma membrane;integral component of plasma membrane;dendrite
• 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