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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
RELT
RELT TNF receptor
Chromosome 11 Β· 11q13.4
NCBI Gene: 84957Ensembl: ENSG00000054967.14HGNC: HGNC:13764UniProt: Q969Z4
28PubMed Papers
21Diseases
0Drugs
8Pathogenic Variants
FUNCTIONAL ROLE
ApoptosisReceptor
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingapoptotic processamelogenesiscytosolamelogenesis imperfectaHypoplastic amelogenesis imperfectahypocalcified amelogenesis imperfectapernicious anemia
✦AI Summary

RELT (RELT TNF receptor) is a member of the tumor necrosis factor receptor superfamily that plays critical roles in dental development, immune regulation, and cellular signaling. RELT is specifically expressed by secretory stage ameloblasts and odontoblasts during tooth development, where it is essential for proper enamel formation 1. Loss-of-function mutations in RELT cause autosomal recessive amelogenesis imperfecta type 3C, characterized by hypoplastic enamel with rapid attrition and altered mechanical properties at the dentino-enamel junction 12. Beyond dental development, RELT functions as an immune-regulatory molecule that may promote immunosuppressive environments in cancer contexts, with T cells from RELT-deficient mice showing increased anti-tumor responses and inflammatory cytokine production 3. RELT activates MAPK14/p38 and MAPK8/JNK signaling pathways and may play a role in apoptosis 4. In multiple myeloma, RELT promotes osteolytic bone lesions by enhancing osteoclast differentiation and maturation 5. RELT physically interacts with related family members RELL1 and RELL2, and all three proteins can be phosphorylated by OSR1 kinase 6. The protein has been strongly conserved across vertebrates, suggesting important physiological functions beyond tooth development 3.

Sources cited
1
RELT is expressed by ameloblasts and odontoblasts during tooth development and mutations cause amelogenesis imperfecta
PMID: 30506946
2
RELT mutations cause autosomal recessive amelogenesis imperfecta with hypoplastic enamel phenotype
PMID: 37670079
3
RELT functions as immune-regulatory molecule and T cells from RELT-deficient mice show increased anti-tumor responses
PMID: 37893069
4
RELT activates MAPK14/p38 and MAPK8/JNK signaling pathways when overexpressed
PMID: 16530727
5
RELT promotes osteolytic bone lesions in multiple myeloma by enhancing osteoclast differentiation
PMID: 38951916
6
RELT interacts with RELL1 and RELL2 family members and is phosphorylated by OSR1 kinase
PMID: 16389068
Disease Associationsβ“˜21
amelogenesis imperfectaOpen Targets
0.52Moderate
Hypoplastic amelogenesis imperfectaOpen Targets
0.40Weak
hypocalcified amelogenesis imperfectaOpen Targets
0.37Weak
pernicious anemiaOpen Targets
0.27Weak
PainOpen Targets
0.24Weak
diverticular diseaseOpen Targets
0.24Weak
Crohn's diseaseOpen Targets
0.23Weak
Varicose veinsOpen Targets
0.22Weak
genetic disorderOpen Targets
0.19Weak
lymphatic system diseaseOpen Targets
0.18Weak
vein disorderOpen Targets
0.18Weak
Hypomaturation amelogenesis imperfectaOpen Targets
0.11Weak
Abnormality of refractionOpen Targets
0.10Weak
breast cancerOpen Targets
0.08Suggestive
nonpapillary renal cell carcinomaOpen Targets
0.08Suggestive
amelogenesis imperfecta hypomaturation type 2A4Open Targets
0.07Suggestive
amelogenesis imperfecta, IIa 1KOpen Targets
0.07Suggestive
amelogenesis imperfecta type 3BOpen Targets
0.07Suggestive
keratosis pilaris atrophicansOpen Targets
0.07Suggestive
neoplasmOpen Targets
0.07Suggestive
Amelogenesis imperfecta 3CUniProt
Pathogenic Variants8
NM_152222.2(RELT):c.521T>G (p.Leu174Arg)Likely pathogenic
Amelogenesis imperfecta
β˜…β˜†β˜†β˜†2023β†’ Residue 174
NM_152222.2(RELT):c.260A>T (p.Asp87Val)Likely pathogenic
Amelogenesis imperfecta
β˜…β˜†β˜†β˜†2023β†’ Residue 87
NM_152222.2(RELT):c.862dup (p.Ala288fs)Likely pathogenic
Amelogenesis imperfecta, type 3C
β˜…β˜†β˜†β˜†2022β†’ Residue 288
NM_152222.2(RELT):c.120+1G>TLikely pathogenic
not provided
β˜†β˜†β˜†β˜†2021
NM_152222.2(RELT):c.164C>T (p.Thr55Ile)Pathogenic
Amelogenesis imperfecta, type 3C
β˜†β˜†β˜†β˜†2019β†’ Residue 55
NM_152222.2(RELT):c.1265G>C (p.Arg422Pro)Pathogenic
Amelogenesis imperfecta, type 3C
β˜†β˜†β˜†β˜†2019β†’ Residue 422
NM_152222.2(RELT):c.121-2A>GPathogenic
Amelogenesis imperfecta, type 3C
β˜†β˜†β˜†β˜†2019
NM_152222.2(RELT):c.1169_1170del (p.Pro390fs)Pathogenic
Amelogenesis imperfecta, type 3C
β˜†β˜†β˜†β˜†2019β†’ Residue 390
View on ClinVar β†—
Related Genes
OXSR1Protein interaction95%TRAF1Protein interaction78%TGFBR2Protein interaction73%TNFRSF19Protein interaction72%ZNF443Shared pathway50%MAGEH1Shared pathway50%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
49%
Brain
15%
Liver
4%
Heart
3%
Ovary
3%
Gene Interaction Network
Click a node to explore
RELTOXSR1TRAF1TGFBR2TNFRSF19ZNF443MAGEH1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q969Z4
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.95LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.72 [0.55–0.95]
RankingsWhere RELT stands among ~20K protein-coding genes
  • #12,431of 20,598
    Most Researched28
  • #3,123of 5,498
    Most Pathogenic Variants8
  • #8,973of 17,882
    Most Constrained (LOEUF)0.95
Genes detectedRELT
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Identification of immune-inflammation targets for intracranial aneurysms: a multiomics and epigenome-wide study integrating summary-data-based Mendelian randomization, single-cell-type expression analysis, and DNA methylation regulation.
PMID: 39051921
Int J Surg Β· 2025
1.00
2
LILRB4 on multiple myeloma cells promotes bone lesion by p-SHP2/NF-ΞΊB/RELT signal pathway.
PMID: 38951916
J Exp Clin Cancer Res Β· 2024
0.90
3
The RELT Family of Proteins: An Increasing Awareness of Their Importance for Cancer, the Immune System, and Development.
PMID: 37893069
Biomedicines Β· 2023
0.80
4
Liver retransplantation: Timing is equally important.
PMID: 37713841
Medicine (Baltimore) Β· 2023
0.70
5
Oro-dental phenotyping and report of three families with RELT-associated amelogenesis imperfecta.
PMID: 37670079
Eur J Hum Genet Β· 2023
0.60