HTR3C

Chr 3

5-hydroxytryptamine receptor 3C

The product of this gene belongs to the ligand-gated ion channel receptor superfamily. This gene encodes subunit C of the type 3 receptor for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor causes fast, depolarizing responses in neurons after activation. Genes encoding subunits C, D and E form a cluster on chromosome 3. [provided by RefSeq, Jul 2008]

OMIMResearchGenerating clinical summary…
MultiplemechanismLOEUF 1.34
Clinical SummaryHTR3C
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
56 VUS of 76 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.34LOEUF
pLI 0.000
Z-score 0.47
OE 0.88 (0.601.34)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
-0.28Z-score
OE missense 1.05 (0.951.16)
261 obs / 248.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.88 (0.601.34)
00.351.4
Missense OE?1.05 (0.951.16)
00.61.4
Synonymous OE?1.03
01.21.6
LoF obs/exp: 16 / 18.2Missense obs/exp: 261 / 248.8Syn Z: -0.24

This gene — mechanism propensity

DN
0.83top 10%
GOF
0.83top 10%
LOF
0.1993th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

76 submitted variants in ClinVar

Classification Summary

VUS56
Likely Benign11
Benign5
56
VUS
11
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
0
56
0
0
56
Likely Benign
0
10
0
1
11
Benign
1
2
0
2
5
Total1680372

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

View in ClinVar →

39 pathogenic / likely-pathogenic (of 44) ClinVar copy-number / structural variants overlap HTR3C — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

HTR3C · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →