HTR5A

Chr 7

5-hydroxytryptamine receptor 5A

Also known as: 5-HT5A

NCBI Gene: 3361 ENSG00000157219 UniProt: P47898

HTR5A encodes a G-protein coupled receptor for serotonin that inhibits adenylate cyclase activity and regulates intracellular calcium release through phosphatidylinositol signaling. The gene is not highly constrained against loss-of-function variants, and no definitive human disease associations have been established for HTR5A mutations in the current literature. This receptor is part of the serotonin neurotransmitter system that broadly influences psychiatric and vascular functions.

ResearchSummary from RefSeq, UniProt

The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) has been implicated in a wide range of psychiatric conditions and also has vasoconstrictive and vasodilatory effects. The gene described in this record is a member of 5-hydroxytryptamine (serotonin) receptor family and encodes a multi-pass membrane protein that functions as a receptor for 5-hydroxytryptamine and couples to G-proteins. This protein has been shown to function in part through the regulation of intracellular Ca2+ mobilization. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.02

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?

1.02LOEUF

pLI 0.006

Z-score 1.52

OE 0.49 (0.25–1.02)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.18Z-score

OE missense 0.97 (0.87–1.08)

237 obs / 245.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.49 (0.25–1.02)

0≤0.351.4

Missense OE?0.97 (0.87–1.08)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 5 / 10.3Missense obs/exp: 237 / 245.0Syn Z: -0.23

Background carrier burden — how many people carry a rare variant somewhere in HTR5A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

535 rare PASS variants

Rare truncating (LoF)

1 in 3,700

56 rare PASS variants

Rare synonymous (reference)

1 in 160

271 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for HTR5A. 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 150	1 in 3,300
South Asian	~43k	1 in 130	1 in 5,400
Remaining (unassigned)	~30k	1 in 100	1 in 6,000
European (Finnish)	~27k	1 in 780	1 in 1,500
Admixed American	~22k	1 in 110	1 in 3,700
African / African American	~21k	1 in 130	≈ 1 in 21,000
East Asian	~20k	1 in 130	1 in 1,600
Ashkenazi Jewish	~13k	1 in 1,000	none seen
Middle Eastern	~2,884	1 in 110	none seen

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 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓