MTNR1B

Chr 11

melatonin receptor 1B

Also known as: FGQTL2, MEL-1B-R, MT2

NCBI Gene: 4544 ENSG00000134640 UniProt: P49286

This gene encodes one of two high affinity forms of a receptor for melatonin, the primary hormone secreted by the pineal gland. This gene product is an integral membrane protein that is a G-protein coupled, 7-transmembrane receptor. It is found primarily in the retina and brain although this detection requires RT-PCR. It is thought to participate in light-dependent functions in the retina and may be involved in the neurobiological effects of melatonin. [provided by RefSeq, Jul 2008]

Research

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.29

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?

1.29LOEUF

pLI 0.001

Z-score 0.96

OE 0.66 (0.36–1.29)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.45Z-score

OE missense 1.09 (0.98–1.21)

233 obs / 214.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.66 (0.36–1.29)

0≤0.351.4

Missense OE?1.09 (0.98–1.21)

0≤0.61.4

Synonymous OE?1.27

0≤1.21.6

LoF obs/exp: 6 / 9.1Missense obs/exp: 233 / 214.3Syn Z: -2.04

Background carrier burden — how many people carry a rare variant somewhere in MTNR1B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 79

596 rare PASS variants

Rare truncating (LoF)

1 in 870

72 rare PASS variants

Rare synonymous (reference)

1 in 130

208 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MTNR1B. 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 110	1 in 2,500
South Asian	~43k	1 in 85	1 in 1,100
Remaining (unassigned)	~30k	1 in 77	1 in 1,700
European (Finnish)	~27k	1 in 270	≈ 1 in 21,000
Admixed American	~22k	1 in 80	1 in 2,700
African / African American	~21k	1 in 73	1 in 1,800
East Asian	~20k	1 in 110	1 in 2,800
Ashkenazi Jewish	~13k	1 in 130	none seen
Middle Eastern	~2,884	1 in 72	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 ↓