HTR4

Chr 5

5-hydroxytryptamine receptor 4

Also known as: 5-HT4, 5-HT4R

NCBI Gene: 3360ENSG00000164270UniProt: Q13639

This gene is a member of the family of serotonin receptors, which are G protein coupled receptors that stimulate cAMP production in response to serotonin (5-hydroxytryptamine). The gene product is a glycosylated transmembrane protein that functions in both the peripheral and central nervous system to modulate the release of various neurotransmitters. Multiple transcript variants encoding proteins with distinct C-terminal sequences have been described. [provided by RefSeq, May 2010]

0
ClinVar variants
0
Pathogenic / LP
0.02
pLI score
0
Active trials
Clinical Summary— HTR4
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.65LOEUF
pLI 0.025
Z-score 2.65
OE 0.33 (0.18–0.65)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.70Z-score
OE missense 0.88 (0.78–0.98)
218 obs / 248.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.33 (0.18–0.65)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.88 (0.78–0.98)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.03
0≤1.21.6
LoF obs/exp: 6 / 18.2Missense obs/exp: 218 / 248.9Syn Z: -0.23

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

HTR4 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
ADAM19 and HTR4 variants and pulmonary function: Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium Targeted Sequencing Study.
London SJ et al.·Circ Cardiovasc Genet
2014Cohort
HTR4 gene structure and altered expression in the developing lung.
Hodge E et al.·Respir Res
2013
Association and CpG SNP analysis of HTR4 polymorphisms with suicidal behavior in subjects with schizophrenia.
Polsinelli G et al.·J Neural Transm (Vienna)
2013
5-Hydroxytryptamine G-Protein-Coupled Receptor Family Genes: Key Players in Cancer Prognosis, Immune Regulation, and Therapeutic Response.
Liu S et al.·Genes (Basel)
2024
Association of 5-hydroxytryptamine (serotonin) receptor 4 (5-HTR4) gene polymorphisms with asthma.
Kim TH et al.·Respirology
2011
Clinical response and side effects of metoclopramide: associations with clinical, demographic, and pharmacogenetic parameters.
Parkman HP et al.·J Clin Gastroenterol
2012
The GG genotype of the serotonin 4 receptor genetic polymorphism, rs1345697, is associated with lower remission rates after antidepressant treatment: Findings from the METADAP cohort.
Poinsignon V et al.·J Affect Disord
2022Cohort
Whole genome sequence analysis of pulmonary function and COPD in 44,287 multi-ancestry participants.
Kim W et al.·Genome Biol
2026
Chronic intestinal pseudo-obstruction: associations with gut microbiota and genes expression of intestinal serotonergic pathway.
Radocchia G et al.·BMC Microbiol
2024
Expression and localization of serotonin receptors in human breast cancer.
Kopparapu PK et al.·Anticancer Res
2013
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools