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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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RTL1
retrotransposon Gag like 1
Chromosome 14 · 14q32.2-q32.31
NCBI Gene: 388015Ensembl: ENSG00000254656.3HGNC: HGNC:14665UniProt: A6NKG5
21PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
placenta developmentskeletal muscle tissue developmentmembraneasthmatype 2 diabetes mellitustype 1 diabetes mellitusdiabetes mellitus
✦AI Summary

RTL1 (retrotransposon Gag like 1) is a paternally expressed, imprinted gene that plays essential roles in placental development, skeletal muscle development, and neurological function 1. The gene is derived from retrotransposon sequences and is crucial for maintaining fetal capillary networks in the placenta during gestation 2. RTL1 is also essential for fetal and neonatal skeletal muscle development, with both deficiency and overexpression causing severe muscle defects and neonatal lethality in mouse models 2. In the nervous system, RTL1 is widely expressed in the central nervous system, including the limbic system, and regulates neuronal excitability in the locus coeruleus 3. The gene mediates anxiety-like behaviors, social behaviors, fear-related learning, and locomotor activity 34. RTL1 expression is controlled by complex imprinting mechanisms involving the DLK1-DIO3 domain, with the maternal allele silenced by the long non-coding RNA MEG3 5. Dysregulation of RTL1 is implicated in Temple syndrome and Kagami-Ogata syndrome, genomic imprinting disorders that affect placental, muscle, and neurological development 16. Additionally, RTL1 expression has been observed in immune cells and is aberrantly expressed in breast cancer tissues 78.

Sources cited
1
RTL1 is a paternally expressed gene in the imprinted DLK1-DIO3 cluster associated with Temple and Kagami-Ogata syndromes
PMID: 32592473
2
RTL1 is essential for placental capillary network maintenance and skeletal muscle development, with deficiency/overexpression causing neonatal lethality
PMID: 32878913
3
RTL1 is paternally expressed in brain regions and regulates neuronal excitability in locus coeruleus, mediating anxiety-like and social behaviors
PMID: 35567414
4
RTL1 is widely expressed in CNS including limbic system and affects locomotor activity, anxiety, and fear responses
PMID: 33484574
5
RTL1 expression is controlled by imprinting mechanisms involving MEG3 lncRNA silencing of the maternal allele
PMID: 38613389
6
RTL1 is a retrotransposon-derived imprinted gene associated with neurodevelopmental disorders
PMID: 37842090
7
RTL1 is aberrantly expressed in breast cancer tissues
PMID: 34087231
8
RTL1 is expressed in immune cells including granulocytes and macrophages
PMID: 37535101
Disease Associationsⓘ20
asthmaOpen Targets
0.23Weak
type 2 diabetes mellitusOpen Targets
0.19Weak
type 1 diabetes mellitusOpen Targets
0.15Weak
diabetes mellitusOpen Targets
0.14Weak
Abruptio PlacentaeOpen Targets
0.12Weak
melanomaOpen Targets
0.11Weak
neoplasmOpen Targets
0.10Weak
experimental autoimmune encephalomyelitisOpen Targets
0.10Weak
Abnormality of the skeletal systemOpen Targets
0.10Weak
infectionOpen Targets
0.10Weak
acute kidney injuryOpen Targets
0.09Suggestive
diastolic heart failureOpen Targets
0.08Suggestive
non-alcoholic fatty liver diseaseOpen Targets
0.08Suggestive
diabetic nephropathyOpen Targets
0.08Suggestive
obesityOpen Targets
0.07Suggestive
mathematical abilityOpen Targets
0.06Suggestive
oropharynx cancerOpen Targets
0.06Suggestive
metabolic syndromeOpen Targets
0.06Suggestive
SplenomegalyOpen Targets
0.06Suggestive
ovarian dysfunctionOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
DIO3Protein interaction92%DLK1Protein interaction92%ZBTB18Shared pathway50%PLAC1Shared pathway50%MYL11Shared pathway33%MYOZ2Shared pathway25%
Tissue Expression6 tissues
Ovary
100%
Brain
16%
Bone Marrow
3%
Liver
1%
Heart
0%
Lung
0%
Gene Interaction Network
Click a node to explore
RTL1DIO3DLK1ZBTB18PLAC1MYL11MYOZ2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt A6NKG5
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.87LoF Tolerant
pLIⓘ
0.32Tolerant
Observed/Expected LoF0.00 [0.00–1.87]
RankingsWhere RTL1 stands among ~20K protein-coding genes
  • #13,999of 20,598
    Most Researched21
  • #17,005of 17,882
    Most Constrained (LOEUF)1.87
Genes detectedRTL1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Temple syndrome and Kagami-Ogata syndrome: clinical presentations, genotypes, models and mechanisms.
PMID: 32592473
Hum Mol Genet · 2020
1.00
2
Roles of retrovirus-derived
PMID: 37842090
Front Cell Dev Biol · 2023
0.90
3
Expression profiling of RTL1 in human breast cancer tissues and cell lines.
PMID: 34087231
Exp Mol Pathol · 2021
0.80
4
Discovery of a novel marker for human granulocytes and tissue macrophages: RTL1 revisited.
PMID: 37535101
Cell Tissue Res · 2023
0.70
5
RTL1/PEG11 imprinted in human and mouse brain mediates anxiety-like and social behaviors and regulates neuronal excitability in the locus coeruleus.
PMID: 35567414
Hum Mol Genet · 2022
0.60