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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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DPF2
double PHD fingers 2
Chromosome 11 Β· 11q13.1
NCBI Gene: 5977Ensembl: ENSG00000133884.11HGNC: HGNC:9964UniProt: J3KMZ8
112PubMed Papers
21Diseases
0Drugs
17Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedTranscription Factor
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
cytosolprotein bindingnucleoplasmhistone H3K9me2/3 reader activityCoffin-Siris syndromeneurodegenerative diseasegenetic disorderIntellectual disability
✦AI Summary

DPF2 (double PHD fingers 2) is a chr11-remodeling subunit that functions as a transcriptional regulator by reading multiple histone modifications. DPF2 binds acetylated histone H3 and H4 tails through its tandem PHD finger domains 1, and additionally recognizes histone lactylation at H3K14la and H3K56ac on the histone globular domain 23. As a component of the BAF (SWI/SNF) chr11-remodeling complex, DPF2 integrates these histone signals to regulate transcription through multiple pathways: it facilitates NRF2-dependent antiinflammatory and antioxidant gene expression 4, suppresses myeloid differentiation of hematopoietic progenitors 1, and regulates macrophage inflammation through CACNA1D-mediated signaling 5. DPF2 exhibits functional complexity through alternative splicing, generating isoforms with distinct chr11 targeting that regulate stem cell maintenance versus neuronal differentiation 6. Beyond transcriptional control, DPF2 acts as an E3 ligase regulating OCT4 protein stability 7. Clinically, DPF2 mutations cause Coffin-Siris syndrome 7, characterized by intellectual disability, developmental delay, and hypotonia 8. Additionally, DPF2-mediated H3K14la recognition drives cervical cancer tumorigenesis 2, establishing it as relevant to cancer pathogenesis.

Sources cited
1
DPF2 binds acetylated histone H3 and H4 tails via PHD domains and mediates myeloid differentiation repression
PMID: 28533407
2
DPF2 reads histone lactylation (H3K14la) to drive oncogenic gene transcription and cervical cancer cell survival
PMID: 39636855
3
DPF2 domain recognizes H3K56ac on histone globular domain and enhances BAF complex nucleosome-remodeling activity
PMID: 39511190
4
DPF2 is a BAF complex subunit required for NRF2-dependent antiinflammatory and antioxidant gene expression in hematopoietic cells
PMID: 37200093
5
DPF2 regulates intestinal inflammation by controlling CACNA1D expression and macrophage polarization via MAPK signaling
PMID: 41223220
6
Alternative DPF2 splicing regulates distinct chromatin targeting programs during stem cell maintenance and neuronal differentiation
PMID: 38701759
7
DPF2 functions as an E3 ligase regulating OCT4 protein ubiquitination, stability, and nuclear distribution
PMID: 26417682
8
DPF2 mutations cause Coffin-Siris syndrome 7, characterized by intellectual disability and developmental delay
PMID: 34205270
Disease Associationsβ“˜21
Coffin-Siris syndromeOpen Targets
0.78Strong
neurodegenerative diseaseOpen Targets
0.55Moderate
genetic disorderOpen Targets
0.47Moderate
Intellectual disabilityOpen Targets
0.37Weak
lysosomal storage diseaseOpen Targets
0.37Weak
Coffin-Siris syndrome 1Open Targets
0.34Weak
hepatocellular carcinomaOpen Targets
0.03Suggestive
cancerOpen Targets
0.03Suggestive
childhood leukemiaOpen Targets
0.02Suggestive
glioblastomaOpen Targets
0.01Suggestive
acute myeloid leukemiaOpen Targets
0.01Suggestive
neoplasmOpen Targets
0.01Suggestive
Lyme diseaseOpen Targets
0.01Suggestive
spinal cord injuryOpen Targets
0.01Suggestive
synovial sarcomaOpen Targets
0.01Suggestive
autism spectrum disorderOpen Targets
0.01Suggestive
developmental disorder of mental healthOpen Targets
0.01Suggestive
influenzaOpen Targets
0.01Suggestive
viral diseaseOpen Targets
0.01Suggestive
infectionOpen Targets
0.00Suggestive
Coffin-Siris syndrome 7UniProt
Pathogenic Variants17
NM_006268.5(DPF2):c.904+1G>APathogenic
Inborn genetic diseases|not provided
β˜…β˜…β˜†β˜†2020
NM_006268.5(DPF2):c.976G>A (p.Glu326Lys)Likely pathogenic
Coffin-Siris syndrome 7
β˜…β˜†β˜†β˜†2025β†’ Residue 326
NM_006268.5(DPF2):c.970T>G (p.Cys324Gly)Likely pathogenic
Coffin-Siris syndrome 7
β˜…β˜†β˜†β˜†2024β†’ Residue 324
NM_006268.5(DPF2):c.899G>T (p.Arg300Leu)Likely pathogenic
Coffin-Siris syndrome 7
β˜…β˜†β˜†β˜†2023β†’ Residue 300
NM_006268.5(DPF2):c.1067G>C (p.Cys356Ser)Likely pathogenic
Coffin-Siris syndrome 7
β˜…β˜†β˜†β˜†2022β†’ Residue 356
NM_006268.5(DPF2):c.1094dup (p.Pro365_Glu366insTer)Likely pathogenic
Coffin-Siris syndrome 7
β˜…β˜†β˜†β˜†2022β†’ Residue 365
NM_006268.5(DPF2):c.1099+2dupLikely pathogenic
Coffin-Siris syndrome 7
β˜…β˜†β˜†β˜†2022
NM_006268.5(DPF2):c.1033T>G (p.Cys345Gly)Likely pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2021β†’ Residue 345
NM_006268.5(DPF2):c.1045G>A (p.Asp349Asn)Pathogenic
not provided
β˜…β˜†β˜†β˜†2020β†’ Residue 349
NM_006268.5(DPF2):c.964T>C (p.Trp322Arg)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2019β†’ Residue 322
NM_006268.5(DPF2):c.1036G>A (p.Asp346Asn)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2019β†’ Residue 346
NM_006268.5(DPF2):c.1049G>A (p.Arg350His)Likely pathogenic
Coffin-Siris syndrome 7|Inborn genetic diseases
β˜…β˜†β˜†β˜†2019β†’ Residue 350
NM_006268.5(DPF2):c.827G>T (p.Cys276Phe)Pathogenic
Coffin-Siris syndrome 7|Coffin-Siris syndrome 1
β˜…β˜†β˜†β˜†2017β†’ Residue 276
NM_006268.5(DPF2):c.1037A>G (p.Asp346Gly)Pathogenic
Coffin-Siris syndrome 7
β˜…β˜†β˜†β˜†β†’ Residue 346
NM_006268.5(DPF2):c.1066T>G (p.Cys356Gly)Pathogenic
Coffin-Siris syndrome 7
β˜…β˜†β˜†β˜†β†’ Residue 356
NM_006268.5(DPF2):c.1099+1G>APathogenic
Coffin-Siris syndrome 7
β˜†β˜†β˜†β˜†2018
NM_006268.5(DPF2):c.990C>G (p.Cys330Trp)Pathogenic
Coffin-Siris syndrome 7
β˜†β˜†β˜†β˜†2018β†’ Residue 330
View on ClinVar β†—
Related Genes
SMARCD1Protein interaction99%SMARCB1Protein interaction99%SMARCA2Protein interaction98%SMARCA4Protein interaction98%ACTL6BProtein interaction98%SMARCC1Protein interaction98%
Tissue Expression6 tissues
Ovary
100%
Heart
74%
Bone Marrow
70%
Brain
68%
Lung
59%
Liver
39%
Gene Interaction Network
Click a node to explore
DPF2SMARCD1SMARCB1SMARCA2SMARCA4ACTL6BSMARCC1
PROTEIN STRUCTURE
Preparing viewer…
PDB5VDC Β· 1.60 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.29Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.17 [0.10–0.29]
RankingsWhere DPF2 stands among ~20K protein-coding genes
  • #4,223of 20,598
    Most Researched112 Β· top quartile
  • #2,334of 5,498
    Most Pathogenic Variants17
  • #1,038of 17,882
    Most Constrained (LOEUF)0.29 Β· top 10%
Genes detectedDPF2
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
DPF2 reads histone lactylation to drive transcription and tumorigenesis.
PMID: 39636855
Proc Natl Acad Sci U S A Β· 2024
1.00
2
PMID: 23556151
0.90
3
The SWI/SNF chromatin-remodeling subunit DPF2 facilitates NRF2-dependent antiinflammatory and antioxidant gene expression.
PMID: 37200093
J Clin Invest Β· 2023
0.80
4
Genotype-Phenotype Correlations in 208 Individuals with Coffin-Siris Syndrome.
PMID: 34205270
Genes (Basel) Β· 2021
0.70
5
Alternative splicing of a chromatin modifier alters the transcriptional regulatory programs of stem cell maintenance and neuronal differentiation.
PMID: 38701759
Cell Stem Cell Β· 2024
0.60