MTNR1A
protein-codingmelatonin receptor 1A, 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 receptor is a G-protein coupled, 7-transmembrane receptor that is responsible for melatonin effects on mammalian circadian rhythm and reproductive alterations affected by day length. The receptor is an integral membrane protein that is readily detectable and localized to two specific regions of the brain. The hypothalamic suprachiasmatic nucleus appears to be involved in circadian rhythm while the hypophysial pars tuberalis may be responsible for the reproductive effects of melatonin. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~28.8 kbGenCC 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 MTNR1A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005958.4. 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 | 2 | 2 | 4 | |||
| missense | 38 | 2 | 2 | 42 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 40 | 4 | 2 | 46 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005949.1 | 2 | MANE Select | |
| Ensembl | ENSP00000302811.5 | 2 | MANE Select | |
| Ensembl | ENSP00000515216.1 | 2 | Standard | |
| RefSeq | XP_011530304.1 | 1 | 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
- adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
- mating behavior
- circadian rhythm
Molecular Function
- protein binding
- melatonin receptor activity
- hormone binding
- organic cyclic compound binding
Cellular Component
- plasma membrane
- integral component of plasma membrane
- receptor complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000307161
- Coding exons
- 2
- Length
- 21913
- Individuals with no LoFs
- 125609
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 139
- Defined
- 125748
- p
- 0.000553
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0919 | 198 | 202 | 0.982 | 0.0000125 | 2267 |
| Missense (PolyPhen) | 34 | 38.324 | 0.88717 | 474 | ||
| Synonymous | -0.00910 | 95 | 94.9 | 1.00 | 0.00000734 | 724 |
| Loss of Function | -0.224 | 9 | 8.30 | 1.08 | 3.64e-7 | 93 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0.0092 | 0.0085 | notable |
| East Asian | 0.00027 | 0.00027 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00038 | 0.00035 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0.00070 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
- 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
- 0.136
Intolerance Scores
- LoFtool
- 0.610
- RVIS EVS
- 0.22
- RVIS percentile EVS
- 68.38
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.729
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |