MTNR1B

protein-coding

melatonin receptor 1B, the group of Melatonin receptors

Gene summary

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]

MANE transcript

NM_005959.5

Inheritance

—

ClinVar variants

U:70B:8

Top phenotype

MTNR1B-related disorder

gnomAD constraint

pLI —, LoF o/e 0.66

Max pathogenic AF

—

Genomic locus

chr11:92,969,651-92,985,066

External References & Databases

Ensembl (ENSG00000134640)

Transcript & Mutation Effects

hg38 • Region Span ~15.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MTNR1B variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 66

MTNR1B-related disorderTotal: 5

Diabetes mellitus type 2, susceptibility toTotal: 4

not providedTotal: 3

Type 2 diabetes mellitusTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005959.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				3 clinvar	1 clinvar	4
missense			70 clinvar	3 clinvar	1 clinvar	74
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	70	6	2	78

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005959.5	RefSeq	NP_005950.1	2	MANE Select
ENST00000257068.3	Ensembl	ENSP00000257068.2	2	MANE Select
ENST00000528076.1	Ensembl	ENSP00000433573.1	2	Standard
ENST00000532482.1	Ensembl	ENSP00000436101.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Circadian entrainment - Homo sapiens (human)
Neuroactive ligand-receptor interaction - Homo sapiens (human)
Small Ligand GPCRs
Melatonin metabolism and effects
GPCRs, Class A Rhodopsin-like

Biological Process

G protein-coupled receptor signaling pathway
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
chemical synaptic transmission
negative regulation of cGMP-mediated signaling
glucose homeostasis

Molecular Function

G protein-coupled receptor activity
protein binding
melatonin receptor activity

Cellular Component

plasma membrane
integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000257068
Coding exons: 2
Length: 15347
Individuals with no LoFs: 125736
Homozygous LoFs: 0
Heterozygous LoFs: 12
Defined: 125748
p: 0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.454	233	214	1.09	0.0000127	2332
Missense (PolyPhen)		54	53.221	1.0146		675
Synonymous	-2.04	119	93.9	1.27	0.00000570	777
Loss of Function	0.962	6	9.14	0.657	4.83e-7	89

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000095	0.000062	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000026	0.000026	rare
South Asian	0.00017	0.00016	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: High affinity receptor for melatonin. Likely to mediate the reproductive and circadian actions of melatonin. The activity of this receptor is mediated by pertussis toxin sensitive G proteins that inhibit adenylate cyclase activity.;

Recessive Scores

pRec: 0.138

Intolerance Scores

LoFtool: 0.356
RVIS EVS: -0.02
RVIS percentile EVS: 52.15

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.231

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium