HTR3A

Chr 11

5-hydroxytryptamine receptor 3A

Also known as: 5-HT-3, 5-HT3A, 5-HT3R, 5HT3R, HTR3

NCBI Gene: 3359 ENSG00000166736 UniProt: P46098

The product of this gene belongs to the ligand-gated ion channel receptor superfamily. This gene encodes subunit A 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. It appears that the heteromeric combination of A and B subunits is necessary to provide the full functional features of this receptor, since either subunit alone results in receptors with very low conductance and response amplitude. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

Research

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.14

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.14LOEUF

pLI 0.000

Z-score 1.03

OE 0.77 (0.53–1.14)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.17Z-score

OE missense 1.19 (1.09–1.30)

350 obs / 293.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.77 (0.53–1.14)

0≤0.351.4

Missense OE?1.19 (1.09–1.30)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 18 / 23.4Missense obs/exp: 350 / 293.6Syn Z: -0.53

Background carrier burden — how many people carry a rare variant somewhere in HTR3A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 69

777 rare PASS variants

Rare truncating (LoF)

1 in 820

104 rare PASS variants

Rare synonymous (reference)

1 in 140

330 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for HTR3A. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 95	1 in 2,200
South Asian	~43k	1 in 52	1 in 830
Remaining (unassigned)	~30k	1 in 71	1 in 570
European (Finnish)	~27k	1 in 310	≈ 1 in 13,000
Admixed American	~22k	1 in 54	1 in 530
African / African American	~21k	1 in 52	1 in 540
East Asian	~20k	1 in 67	1 in 540
Ashkenazi Jewish	~13k	1 in 170	none seen
Middle Eastern	~2,884	1 in 60	≈ 1 in 580

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 9 coding exons well covered in gnomAD exomes and genomes.? see exons ↓