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7 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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RWDD1
RWD domain containing 1
Chromosome 6 · 6q22.1
NCBI Gene: 51389Ensembl: ENSG00000111832.13HGNC: HGNC:20993UniProt: Q9H446
28PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingandrogen receptor signaling pathwaytranscription coactivator activitycytoplasmic translationneurodegenerative diseaseDNA methylationpoisoningulcerative colitis
✦AI Summary

RWDD1 (RWD domain containing 1) is an intrinsically unstructured protein with multifaceted cellular functions. Primarily, RWDD1 acts as a coactivator of the androgen receptor (AR) transcription factor, interacting with the AR ligand binding domain to enhance androgen-dependent transactivation 1. This function is particularly important during male genital development, where RWDD1 was identified as an AR-interacting protein in embryonic genital tissue 1. Beyond AR signaling, RWDD1 can function as a transcription factor itself, binding DNA promoter regions to regulate gene expression, as demonstrated in mitochondrial sulfide metabolism pathways 2. RWDD1 expression is dynamically regulated during aging and stress. Thymic RWDD1 expression decreases in aged and oxidatively stressed mice, suggesting a role in thymus involution and immune aging 3. Recent longevity studies identified RWDD1 as a strong candidate gene for human longevity, with long-lived individuals showing a statistically significant burden of rare missense variants, potentially involving mTOR signaling pathways 4. Clinically, RWDD1 expression associates with lithium adverse effects, particularly tremor and xerostomia, in psychiatric patients 5. Additionally, RWDD1 emerged as a candidate gene in obsessive-compulsive disorder pathogenesis through transcriptomic analysis 6.

Sources cited
1
RWDD1 interacts with AR ligand binding domain and functions as a coactivator of androgen-dependent transactivation
PMID: 22406838
2
RWDD1 emerged as strong candidate gene for longevity with statistically significant burden of rare missense variants in long-lived individuals
PMID: 40232348
3
RWDD1 is thymus aging-related protein with decreased expression in aged and oxidatively stressed mice
PMID: 18761815
4
RWDD1 functions as transcription factor binding DNA promoter regions to regulate gene expression
PMID: 30278355
5
RWDD1 expression associates with lithium adverse effects including tremor and xerostomia in psychiatric patients
PMID: 34320404
6
RWDD1 identified as candidate gene in obsessive-compulsive disorder through weighted gene co-expression network analysis
PMID: 38664915
7
RWDD1 is member of intrinsically unstructured protein family containing RWD domain
PMID: 18954556
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.33Weak
DNA methylationOpen Targets
0.28Weak
poisoningOpen Targets
0.28Weak
ulcerative colitisOpen Targets
0.28Weak
retinitis pigmentosa and erythrocytic microcytosisOpen Targets
0.04Suggestive
22q11.2 deletion syndromeOpen Targets
0.03Suggestive
malariaOpen Targets
0.03Suggestive
ghosal hematodiaphyseal dysplasiaOpen Targets
0.03Suggestive
Subcutaneous Panniculitis-Like T-Cell LymphomaOpen Targets
0.03Suggestive
immunodeficiency 80 with or without congenital cardiomyopathyOpen Targets
0.03Suggestive
megaloblastic anemia, folate-responsiveOpen Targets
0.03Suggestive
Niemann-Pick disease type BOpen Targets
0.03Suggestive
X-Linked Combined Immunodeficiency DiseasesOpen Targets
0.03Suggestive
cancerOpen Targets
0.01Suggestive
melanomaOpen Targets
0.01Suggestive
juvenile dermatomyositisOpen Targets
0.00Suggestive
multiple myelomaOpen Targets
0.00Suggestive
colorectal cancerOpen Targets
0.00Suggestive
hereditary spastic paraplegiaOpen Targets
0.00Suggestive
xerostomiaOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
GCN1Protein interaction96%DENRProtein interaction83%DRG2Protein interaction81%ZC3H15Protein interaction73%DRG1Protein interaction71%SCGB2A2Shared pathway50%
Tissue Expression6 tissues
Heart
100%
Brain
89%
Bone Marrow
65%
Ovary
61%
Lung
54%
Liver
43%
Gene Interaction Network
Click a node to explore
RWDD1GCN1DENRDRG2ZC3H15DRG1SCGB2A2
PROTEIN STRUCTURE
Preparing viewer…
PDB2EBM · NMR
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.65LoF Tolerant
pLIⓘ
0.82Intermediate
Observed/Expected LoF0.25 [0.11–0.65]
RankingsWhere RWDD1 stands among ~20K protein-coding genes
  • #12,436of 20,598
    Most Researched28
  • #4,751of 17,882
    Most Constrained (LOEUF)0.65
Genes detectedRWDD1
Sources retrieved7 papers
Response time—
📄 Sources
7▼
1
German longevity study reveals novel rare pro-longevity alleles clustering in mTOR signaling pathway.
PMID: 40232348
Geroscience · 2025
1.00
2
Identification of key mRNAs and signaling pathways in obsessive compulsive disorder based on weighted gene co-expression network analysis and cytoHubba plugin.
PMID: 38664915
Brain Behav · 2024
0.86
3
Dose-dependent transcriptional effects of lithium and adverse effect burden in a psychiatric cohort.
PMID: 34320404
Prog Neuropsychopharmacol Biol Psychiatry · 2022
0.71
4
RWDD1 interacts with the ligand binding domain of the androgen receptor and acts as a coactivator of androgen-dependent transactivation.
PMID: 22406838
Mol Cell Endocrinol · 2012
0.57
5
Identification and characterization of a novel thymus aging related protein Rwdd1.
PMID: 18761815
Cell Mol Immunol · 2008
0.43