HTR1D

Chr 1

5-hydroxytryptamine receptor 1D

Also known as: 5-HT1D, HT1DA, HTR1DA, HTRL, RDC4

NCBI Gene: 3352 ENSG00000179546 UniProt: P28221 OMIM: 182133

HTR1D encodes a G-protein coupled receptor for serotonin that inhibits adenylate cyclase activity and regulates neurotransmitter release in the brain. Mutations cause autosomal dominant episodic cranial sensory neuropathy with onset typically in childhood or adolescence. The gene shows low constraint to loss-of-function variation, suggesting that complete loss of function may be tolerated.

OMIM ResearchSummary from RefSeq, UniProt

Enables Gi/o-coupled serotonin receptor activity. Involved in adenylate cyclase-inhibiting serotonin receptor signaling pathway and intestine smooth muscle contraction. Located in plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.30

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.30LOEUF

pLI 0.001

Z-score 0.96

OE 0.66 (0.36–1.30)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.09Z-score

OE missense 0.98 (0.88–1.10)

221 obs / 224.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.66 (0.36–1.30)

0≤0.351.4

Missense OE?0.98 (0.88–1.10)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 6 / 9.1Missense obs/exp: 221 / 224.8Syn Z: 0.27

Background carrier burden — how many people carry a rare variant somewhere in HTR1D?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 76

490 rare PASS variants

Rare truncating (LoF)

1 in 3,500

66 rare PASS variants

Rare synonymous (reference)

1 in 290

208 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for HTR1D. 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 120	1 in 3,900
South Asian	~43k	1 in 100	1 in 3,900
Remaining (unassigned)	~30k	1 in 79	1 in 6,000
European (Finnish)	~27k	1 in 760	≈ 1 in 27,000
Admixed American	~22k	1 in 86	1 in 3,700
African / African American	~21k	1 in 110	1 in 2,400
East Asian	~20k	1 in 120	1 in 1,800
Ashkenazi Jewish	~13k	1 in 240	≈ 1 in 13,000
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 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓