HTR1E

Chr 6

5-hydroxytryptamine receptor 1E

Also known as: 5-HT1E

NCBI Gene: 3354ENSG00000168830UniProt: P28566

Enables Gi/o-coupled serotonin receptor activity; serotonin binding activity; and serotonin receptor activity. Involved in adenylate cyclase-inhibiting serotonin receptor signaling pathway. Located in plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

64
ClinVar variants
16
Pathogenic / LP
0.29
pLI score
0
Active trials
Clinical Summary— HTR1E
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.
📋
ClinVar Variants
16 Pathogenic / Likely Pathogenic· 43 VUS of 64 total submissions

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.
0.78LOEUF
pLI 0.293
Z-score 1.98
OE 0.25 (0.10–0.78)
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.
1.71Z-score
OE missense 0.67 (0.59–0.77)
145 obs / 215.6 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.0.25 (0.10–0.78)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.67 (0.59–0.77)
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.0.98
0≤1.21.6
LoF obs/exp: 2 / 8.1Missense obs/exp: 145 / 215.6Syn Z: 0.12

ClinVar Variant Classifications

64 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15
Likely Pathogenic1
VUS43
Likely Benign4
Benign1
15
Pathogenic
1
Likely Pathogenic
43
VUS
4
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
15
0
15
Likely Pathogenic
0
0
1
0
1
VUS
0
31
12
0
43
Likely Benign
0
2
1
1
4
Benign
0
0
0
1
1
Total03329264

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

HTR1E · 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
Serotonin/HTR1E signaling blocks chronic stress-promoted progression of ovarian cancer.
Qin X et al.·Theranostics
2021
A genome-wide association study of female sexual dysfunction.
Burri A et al.·PLoS One
2012
Genome-wide association of an integrated osteoporosis-related phenotype: is there evidence for pleiotropic genes?
Karasik D et al.·J Bone Miner Res
2012
Correlation of BRCA2 gene mutation and prognosis as well as variant genes in invasive urothelial carcinoma of the bladder.
Kuang S et al.·Cancer Biomark
2019
The phenotypic spectrum of proximal 6q deletions based on a large cohort derived from social media and literature reports.
Engwerda A et al.·Eur J Hum Genet
2018Cohort
Genome-wide association scan of quantitative traits for attention deficit hyperactivity disorder identifies novel associations and confirms candidate gene associations.
Lasky-Su J et al.·Am J Med Genet B Neuropsychiatr Genet
2008
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Experimental Validation of the Neurotrophic Factor-α1 Binding Site on the Serotonin Receptor 1E (HTR1E) Responsible for β-Arrestin Activation and Subsequent Neuroprotection.
Yang X et al.·ACS Omega
2024🔓 Open Access
The discovery, structure, and function of 5-HTR1E serotonin receptor.
Sharma VK et al.·Cell Commun Signal
2023🔓 Open Access
Characterization of serotonin-5-HTR1E signaling pathways and its role in cell survival.
Sharma VK et al.·FASEB J
2023
Novel interaction between neurotrophic factor-α1/carboxypeptidase E and serotonin receptor, 5-HTR1E, protects human neurons against oxidative/neuroexcitotoxic stress via β-arrestin/ERK signaling.
Sharma VK et al.·Cell Mol Life Sci
2021🔓 Open Access
Molecular Cloning and Functional Characterization of Three 5-HT Receptor Genes (HTR1B, HTR1E, and HTR1F) in Chickens.
Sun C et al.·Genes (Basel)
2021🔓 Open AccessFunctional
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools