HTR2C

protein-coding

5-hydroxytryptamine receptor 2C, the group of 5-hydroxytryptamine receptors, G protein-coupled|Small nucleolar RNA protein coding host genes|MicroRNA protein coding host genes

Gene summary

This gene encodes a seven-transmembrane G-protein-coupled receptor. The encoded protein responds to signaling through the neurotransmitter serotonin. The mRNA of this gene is subject to multiple RNA editing events, where adenosine residues encoded by the genome are converted to inosines. RNA editing is predicted to alter the structure of the second intracellular loop, thereby generating alternate protein forms with decreased ability to interact with G proteins. Abnormalities in RNA editing of this gene have been detected in victims of suicide that suffer from depression. In addition, naturally-occuring variation in the promoter and 5' non-coding and coding regions of this gene may show statistically-significant association with mental illness and behavioral disorders. Alternative splicing results in multiple different transcript variants. [provided by RefSeq, Jan 2015]

Previous symbols:

HTR1C

MANE transcript

NM_000868.4

Inheritance

ClinVar variants

P:1U:130B:45

Top phenotype

obesity disorder

gnomAD constraint

pLI —, LoF o/e 0.38

Max pathogenic AF

—

Genomic locus

chrX:114,584,078-114,910,061

External References & Databases

Ensembl (ENSG00000147246)

Transcript & Mutation Effects

hg38 • Region Span ~326.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

obesity disorderSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0011122

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HTR2C variants in ClinVar

5 Conditions Cataloged

HTR2C-related disorderTotal: 134

not specifiedTotal: 33

not providedTotal: 5

Prostate cancerTotal: 1

Inborn genetic diseasesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000868.4. 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			19 clinvar	37 clinvar		56
missense			105 clinvar	8 clinvar		113
nonsense			3 clinvar			3
start loss			1 clinvar			1
frameshift		1 clinvar	1 clinvar			2
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	1	130	45	0	176

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 12 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000868.4	RefSeq	NP_000859.2	4	MANE Select
ENST00000276198.6	Ensembl	ENSP00000276198.1	4	MANE Select
NM_001256760.3	RefSeq	NP_001243689.2	4	Standard
NM_001256761.3	RefSeq	NP_001243690.2	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Inflammatory mediator regulation of TRP channels - Homo sapiens (human)
Serotonergic synapse - Homo sapiens (human)
Gap junction - Homo sapiens (human)
Calcium signaling pathway - Homo sapiens (human)
Neuroactive ligand-receptor interaction - Homo sapiens (human)

Biological Process

behavioral fear response
cellular calcium ion homeostasis
G protein-coupled receptor signaling pathway
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
phospholipase C-activating G protein-coupled receptor signaling pathway

Molecular Function

Gq/11-coupled serotonin receptor activity
G protein-coupled receptor activity
G protein-coupled serotonin receptor activity
drug binding
neurotransmitter receptor activity

Cellular Component

plasma membrane
integral component of plasma membrane
dendrite

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000276198
Coding exons: 4
Length: 326074
Individuals with no LoFs: 125714
Homozygous LoFs: 2
Heterozygous LoFs: 3
Defined: 125719
p: 0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.21	147	194	0.756	0.0000159	3008
Missense (PolyPhen)		21	55.351	0.3794		901
Synonymous	0.960	70	81.0	0.864	0.00000736	935
Loss of Function	1.87	4	10.6	0.379	8.59e-7	168

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000077	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000026	0.000018	rare
South Asian	0.000057	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1- 2,5,-dimethoxy-4-iodophenyl-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca(2+) ions from intracellular stores. Regulates neuronal activity via the activation of short transient receptor potential calcium channels in the brain, and thereby modulates the activation of pro-opiomelacortin neurons and the release of CRH that then regulates the release of corticosterone. Plays a role in the regulation of appetite and eating behavior, responses to anxiogenic stimuli and stress. Plays a role in insulin sensitivity and glucose homeostasis. {ECO:0000269|PubMed:12970106, ECO:0000269|PubMed:18703043, ECO:0000269|PubMed:19057895, ECO:0000269|PubMed:7895773}.;

Recessive Scores

pRec: 0.224

Intolerance Scores

LoFtool: 0.704
RVIS EVS: -0.27
RVIS percentile EVS: 34.32

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.710

Gene Damage Prediction

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