DPF2

Chr 11AD

double PHD fingers 2

Also known as: CSS7, REQ, SMARCG2, UBID4, ubi-d4

NCBI Gene: 5977ENSG00000133884UniProt: Q92785

The protein encoded by this gene is a member of the d4 domain family, characterized by a zinc finger-like structural motif. This protein functions as a transcription factor which is necessary for the apoptotic response following deprivation of survival factors. It likely serves a regulatory role in rapid hematopoietic cell growth and turnover. This gene is considered a candidate gene for multiple endocrine neoplasia type I, an inherited cancer syndrome involving multiple parathyroid, enteropancreatic, and pituitary tumors. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Coffin-Siris syndrome 7MIM #618027
AD
269
ClinVar variants
25
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— DPF2
🧬
Gene-Disease Validity (ClinGen)
Coffin-Siris syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
25 Pathogenic / Likely Pathogenic· 108 VUS of 269 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.16LOEUF
pLI 1.000
Z-score 4.86
OE 0.03 (0.01–0.16)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.90Z-score
OE missense 0.48 (0.41–0.56)
117 obs / 244.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.03 (0.01–0.16)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.48 (0.41–0.56)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.03
0≤1.21.6
LoF obs/exp: 1 / 29.4Missense obs/exp: 117 / 244.5Syn Z: -0.24

ClinVar Variant Classifications

269 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic12
VUS108
Likely Benign109
Benign14
Conflicting13
13
Pathogenic
12
Likely Pathogenic
108
VUS
109
Likely Benign
14
Benign
13
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
5
6
0
13
Likely Pathogenic
2
8
2
0
12
VUS
4
91
9
4
108
Likely Benign
1
8
53
47
109
Benign
0
3
7
4
14
Conflicting
—13
Total91157755269

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

DPF2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

DPF2-related Coffin-Siris like disorder

strong
ADDominant NegativeAltered Gene Product Structure
Dev. DisordersSkin
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Coffin-Siris syndrome 7

MIM #618027

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — DPF2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genotype-Phenotype Correlations in 208 Individuals with Coffin-Siris Syndrome.
Vasko A et al.·Genes (Basel)
2021
The SWI/SNF chromatin-remodeling subunit DPF2 regulates macrophage inflammation in intestinal injury via the CACNA1D-mediated MAPK pathway.
Ji M et al.·Proc Natl Acad Sci U S A
2025Functional
Mutations in the BAF-Complex Subunit DPF2 Are Associated with Coffin-Siris Syndrome.
Vasileiou G et al.·Am J Hum Genet
2018
DPF2-related Coffin-Siris syndrome type 7 in two generations.
Kolokotronis K et al.·Eur J Med Genet
2024Case report
A new missense mutation in DPF2 gene related to Coffin Siris syndrome 7: Description of a mild phenotype expanding DPF2-related clinical spectrum and differential diagnosis among similar syndromes epigenetically determined.
Milone R et al.·Brain Dev
2020Case report
Deleterious variants in intolerant genes reveal new candidates for self-limited delayed puberty.
Rezende RC et al.·Eur J Endocrinol
2025
Expanding the phenotypic spectrum associated with DPF2: A new case report.
Knapp KM et al.·Am J Med Genet A
2019Case report
Congenital diaphragmatic hernia in Coffin Siris syndrome: Further evidence from two cases.
Rimoldi M et al.·Am J Med Genet A
2023Case report
Evidence for an association between Coffin-Siris syndrome and congenital diaphragmatic hernia.
Gofin Y et al.·Am J Med Genet A
2022Review
Crotonylation and the Risk of Head and Neck Cancer: Insights from a Two-Sample Mendelian Randomization Study.
Zhang D et al.·Int Dent J
2026
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools