HRH3

histamine receptor H3, the group of Histamine receptors

Basic information

Region (hg38): 20:62214959-62220278

Links

ENSG00000101180 ∙ NCBI:11255 ∙ OMIM:604525 ∙ HGNC:5184 ∙ Uniprot:Q9Y5N1 ∙ 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 HRH3 gene.

• Inborn genetic diseases (14 variants)
• not provided (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HRH3 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				3	2	5
missense			14			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	14	3	2

Variants in HRH3

This is a list of pathogenic ClinVar variants found in the HRH3 region.

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

Position	Type	Phenotype	Significance	ClinVar
20-62216129-C-T			Benign/Likely benign (Oct 01, 2023)
20-62216190-T-C		not specified	Uncertain significance (Jan 16, 2024)
20-62216312-G-A			Benign (Apr 10, 2018)
20-62216338-G-A		not specified	Uncertain significance (Jan 27, 2022)
20-62216362-C-A		not specified	Uncertain significance (Dec 09, 2023)
20-62216409-C-T		not specified	Uncertain significance (May 17, 2023)
20-62216422-C-T		not specified	Uncertain significance (Jan 20, 2023)
20-62216430-G-A		not specified	Uncertain significance (May 31, 2023)
20-62216433-G-A		not specified	Uncertain significance (Jan 30, 2024)
20-62216470-C-T		not specified	Uncertain significance (Sep 15, 2021)
20-62216487-G-T		not specified	Uncertain significance (Jan 26, 2022)
20-62216493-G-A		not specified	Uncertain significance (Feb 01, 2023)
20-62216546-G-A			Likely benign (Nov 01, 2023)
20-62216574-C-G		not specified	Uncertain significance (Dec 14, 2023)
20-62216605-C-T		not specified	Uncertain significance (Jan 11, 2023)
20-62216613-G-A		not specified	Uncertain significance (Sep 20, 2023)
20-62216634-C-T		not specified	Uncertain significance (Mar 30, 2022)
20-62216638-C-A		not specified	Uncertain significance (Jun 29, 2023)
20-62216650-G-A		not specified	Uncertain significance (Oct 13, 2023)
20-62216742-G-A		not specified	Uncertain significance (May 10, 2022)
20-62216898-G-A		not specified	Uncertain significance (Jan 09, 2024)
20-62218602-G-A			Likely benign (Feb 01, 2023)
20-62219725-G-A			Benign (Dec 31, 2019)
20-62219906-G-A		not specified	Uncertain significance (Jul 07, 2022)
20-62219951-T-A		not specified	Uncertain significance (Mar 07, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HRH3	protein_coding	protein_coding	ENST00000340177	3	5298

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0408	0.953	125362	0	5	125367	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.27	169	275	0.614	0.0000180	2791
Missense in Polyphen		61	103.96	0.58674		1004
Synonymous	0.238	125	128	0.973	0.00000839	992
Loss of Function	2.42	5	15.2	0.330	7.50e-7	144

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000284	0.0000265
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: The H3 subclass of histamine receptors could mediate the histamine signals in CNS and peripheral nervous system. Signals through the inhibition of adenylate cyclase and displays high constitutive activity (spontaneous activity in the absence of agonist). Agonist stimulation of isoform 3 neither modified adenylate cyclase activity nor induced intracellular calcium mobilization.
• Pathway: Neuroactive ligand-receptor interaction - Homo sapiens (human);GPCRs, Class A Rhodopsin-like;Monoamine Transport;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: 0.140

Intolerance Scores

• loftool: 0.163
• rvis_EVS: -0.38
• rvis_percentile_EVS: 27.69

Haploinsufficiency Scores

• pHI: 0.131
• hipred: Y
• hipred_score: 0.735
• ghis: 0.653

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.916

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hrh3
• 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); immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); growth/size/body region phenotype; 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); homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: hrh3
• Affected structure: sleep
• Phenotype tag: abnormal
• Phenotype quality: behavioral quality of a process

Gene ontology

• Biological process: 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;chemical synaptic transmission;neurotransmitter secretion;negative regulation of glutamate secretion;regulation of norepinephrine secretion;negative regulation of serotonin secretion;cognition;G protein-coupled serotonin receptor signaling pathway
• Cellular component: plasma membrane;integral component of plasma membrane;dendrite;presynapse
• 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