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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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DAAM2
dishevelled associated activator of morphogenesis 2
Chromosome 6 Β· 6p21.2
NCBI Gene: 23500Ensembl: ENSG00000146122.17HGNC: HGNC:18143UniProt: A0A0J9YYF7
32PubMed Papers
21Diseases
0Drugs
5Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
podocyte cell migrationnucleoplasmextracellular exosomeprotein bindingnephrotic syndrome, type 24Abnormality of the skeletal systemsteroid-resistant nephrotic syndromefamilial idiopathic steroid-resistant nephrotic syndrome
✦AI Summary

DAAM2 is a formin family protein that serves as a key regulator of Wnt signaling pathways essential for embryonic development and tissue homeostasis. As a downstream effector of Wnt ligands, DAAM2 promotes canonical Wnt signaling by clustering Disheveled complexes and organizing Wnt receptor signalosomes through its association with Rac1 and the actin cytoskeleton 1. DAAM2 also regulates non-canonical Wnt signaling, influencing left/right asymmetry and myocardial maturation 2. The protein functions as an actin nucleator and regulator of filopodia formation and cell migration 3. During central nervous system development, DAAM2 suppresses oligodendrocyte differentiation via PIP5K1A interaction and regulates myelin compaction through Rac1-dependent modulation of Gelsolin levels, promoting ubiquitination and degradation of Gelsolin to control the oligodendrocyte actin cytoskeleton 4. In steroid hormone signaling, DAAM2 localizes to the nucleus where it polymerizes actin at androgen receptors to facilitate transcriptional droplet formation and gene expression 3. Clinically, DAAM2 mutations cause androgen insensitivity syndrome and nephrotic syndrome 24 5. Loss of DAAM2 function correlates with decreased bone strength independent of mineralization 6, while elevated DAAM2 associates with fetal growth restriction through hypoxia-dependent placental dysfunction 7. Recent evidence implicates DAAM2 in bone homeostasis through regulation of immune-mediated senescent osteoblast clearance 8.

Sources cited
1
DAAM2 regulates canonical Wnt signaling by clustering Wnt receptor signalosomes through Rac1 and actin polymerization
PMID: 33310913
2
DAAM2 is a formin-homology FDD subfamily protein expressed in multiple tissues and plays roles in Wnt signaling
PMID: 12632087
3
DAAM2 mutations cause androgen insensitivity syndrome; DAAM2 polymerizes nuclear actin at androgen receptors to promote transcriptional droplets
PMID: 36972684
4
DAAM2 regulates oligodendrocyte differentiation and myelin structure through Rac1 and Gelsolin via ubiquitination-mediated degradation
PMID: 35101966
5
DAAM2 mutations cause multiple inherited disorders including intellectual disability, renal disease, and cardiomyopathy
PMID: 34685534
6
DAAM2 knockout mice show disproportionate decrease in bone strength relative to mineralization
PMID: 30598549
7
DAAM2 is elevated in circulation and placenta in fetal growth restriction pregnancies and is regulated by hypoxia
PMID: 33692394
8
DAAM2 serves as downstream effector for SIRT1 in regulating bone homeostasis through immune cell activation
PMID: 40714829
Disease Associationsβ“˜21
nephrotic syndrome, type 24Open Targets
0.51Moderate
Abnormality of the skeletal systemOpen Targets
0.47Moderate
steroid-resistant nephrotic syndromeOpen Targets
0.37Weak
familial idiopathic steroid-resistant nephrotic syndromeOpen Targets
0.37Weak
nervous system benign neoplasmOpen Targets
0.33Weak
alcohol drinkingOpen Targets
0.32Weak
adolescent idiopathic scoliosisOpen Targets
0.32Weak
aortic atherosclerosisOpen Targets
0.31Weak
Umbilical herniaOpen Targets
0.31Weak
type 2 diabetes mellitusOpen Targets
0.29Weak
hypospadiasOpen Targets
0.28Weak
genetic disorderOpen Targets
0.19Weak
encephalopathy due to sulfite oxidase deficiencyOpen Targets
0.19Weak
sulfite oxidase deficiency due to molybdenum cofactor deficiency type AOpen Targets
0.19Weak
sulfite oxidase deficiency due to molybdenum cofactor deficiencyOpen Targets
0.16Weak
idiopathic multidrug-resistant nephrotic syndromeOpen Targets
0.12Weak
neoplasmOpen Targets
0.08Suggestive
gliomaOpen Targets
0.08Suggestive
hepatocellular carcinomaOpen Targets
0.08Suggestive
pancreatic adenocarcinomaOpen Targets
0.07Suggestive
Nephrotic syndrome 24UniProt
Pathogenic Variants5
NM_001201427.2(DAAM2):c.3058G>T (p.Gly1020Ter)Likely pathogenic
Nephrotic syndrome, type 24
β˜…β˜†β˜†β˜†2025β†’ Residue 1020
NM_001201427.2(DAAM2):c.196C>T (p.Arg66Ter)Likely pathogenic
Nephrotic syndrome, type 24
β˜…β˜†β˜†β˜†β†’ Residue 66
NM_001201427.2(DAAM2):c.361G>C (p.Glu121Gln)Pathogenic
Nephrotic syndrome, type 24
β˜†β˜†β˜†β˜†2021β†’ Residue 121
NM_001201427.2(DAAM2):c.1004G>A (p.Arg335Gln)Pathogenic
Nephrotic syndrome, type 24
β˜†β˜†β˜†β˜†2021β†’ Residue 335
NM_001201427.2(DAAM2):c.1333C>T (p.Arg445Ter)Pathogenic
Nephrotic syndrome, type 24
β˜†β˜†β˜†β˜†2021β†’ Residue 445
View on ClinVar β†—
Related Genes
DVL1Protein interaction94%DVL2Protein interaction94%DVL3Protein interaction94%DAAM1Protein interaction94%PFN4Protein interaction76%RHOAProtein interaction72%
Tissue Expression6 tissues
Brain
100%
Lung
29%
Heart
24%
Ovary
21%
Liver
13%
Bone Marrow
6%
Gene Interaction Network
Click a node to explore
DAAM2DVL1DVL2DVL3DAAM1PFN4RHOA
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q86T65
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.49Moderately Constrained
pLIβ“˜
0.98Intolerant
Observed/Expected LoF0.37 [0.28–0.49]
RankingsWhere DAAM2 stands among ~20K protein-coding genes
  • #11,495of 20,598
    Most Researched32
  • #3,616of 5,498
    Most Pathogenic Variants5
  • #2,872of 17,882
    Most Constrained (LOEUF)0.49 Β· top quartile
Genes detectedDAAM2
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
An atlas of genetic influences on osteoporosis in humans and mice.
PMID: 30598549
Nat Genet Β· 2019
1.00
2
Identification and characterization of human DAAM2 gene in silico.
PMID: 12632087
Int J Oncol Β· 2003
0.90
3
Formin-mediated nuclear actin at androgen receptors promotes transcription.
PMID: 36972684
Nature Β· 2023
0.80
4
Daam2 Regulates Myelin Structure and the Oligodendrocyte Actin Cytoskeleton through Rac1 and Gelsolin.
PMID: 35101966
J Neurosci Β· 2022
0.70
5
Formins in Human Disease.
PMID: 34685534
Cells Β· 2021
0.60