DPF2

Summary

DPF2 (double PHD fingers 2, HGNC:9964) is a protein-coding gene on chromosome 11q13.1, encoding Zinc finger protein ubi-d4 (Q92785). Plays an active role in transcriptional regulation by binding modified histones H3 and H4. It is a selective cancer dependency (DepMap: 34.1% of cell lines).

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.

Source: NCBI Gene 5977 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Coffin-Siris syndrome (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 274 total — 7 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 103
• Cancer dependency (DepMap): dependent in 34.1% of screened cell lines
• MANE Select transcript: NM_006268

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9964
Approved symbol	DPF2
Name	double PHD fingers 2
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Aliases	ubi-d4, BAF45d, SMARCG2
Ensembl gene	ENSG00000133884
Ensembl biotype	protein_coding
OMIM	601671
Entrez	5977

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 9 protein_coding, 6 retained_intron, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000252268, ENST00000415073, ENST00000444314, ENST00000524666, ENST00000528416, ENST00000530973, ENST00000530993, ENST00000531989, ENST00000532052, ENST00000532102, ENST00000532264, ENST00000532492, ENST00000703393, ENST00000703394, ENST00000703424, ENST00000703425, ENST00000703426, ENST00000703427, ENST00000938273

RefSeq mRNA: 2 — MANE Select: NM_006268 NM_001330308, NM_006268

CCDS: CCDS8100, CCDS81583

Canonical transcript exons

ENST00000528416 — 11 exons

Exon	Start	End
ENSE00003498334	65345666	65345803
ENSE00003502485	65340966	65341073
ENSE00003503966	65345930	65346058
ENSE00003526071	65340385	65340545
ENSE00003541428	65343745	65343837
ENSE00003653840	65341399	65341562
ENSE00003663834	65343991	65344069
ENSE00003988870	65346247	65346359
ENSE00003988872	65333852	65333918
ENSE00003988873	65348850	65348931
ENSE00003988876	65351683	65354262

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 98.69.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 38.1314 / max 234.2335, expressed in 1813 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115068	38.1314	1813

Top tissues by expression

300 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	98.69	gold quality
secondary oocyte	CL:0000655	98.40	gold quality
calcaneal tendon	UBERON:0003701	96.48	gold quality
ventricular zone	UBERON:0003053	95.64	gold quality
body of uterus	UBERON:0009853	95.12	gold quality
right ovary	UBERON:0002118	94.98	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.88	gold quality
lower esophagus	UBERON:0013473	94.86	gold quality
left ovary	UBERON:0002119	94.78	gold quality
endometrium epithelium	UBERON:0004811	94.78	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.65	gold quality
ganglionic eminence	UBERON:0004023	94.48	gold quality
endocervix	UBERON:0000458	94.14	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.11	gold quality
left uterine tube	UBERON:0001303	93.94	gold quality
smooth muscle tissue	UBERON:0001135	93.90	gold quality
right uterine tube	UBERON:0001302	93.78	gold quality
popliteal artery	UBERON:0002250	93.78	gold quality
mucosa of stomach	UBERON:0001199	93.77	gold quality
tibial artery	UBERON:0007610	93.77	gold quality
granulocyte	CL:0000094	93.69	gold quality
apex of heart	UBERON:0002098	93.64	gold quality
right coronary artery	UBERON:0001625	93.60	gold quality
descending thoracic aorta	UBERON:0002345	93.53	gold quality
stromal cell of endometrium	CL:0002255	93.39	gold quality
aorta	UBERON:0000947	93.32	gold quality
Brodmann (1909) area 10	UBERON:0013541	93.18	gold quality
right testis	UBERON:0004534	93.12	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.11	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.08	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.76

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

miRNA regulators (miRDB)

80 targeting DPF2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-3616-5P	99.55	67.02	989
HSA-MIR-573	99.55	67.44	955
HSA-MIR-4708-3P	99.51	67.99	870
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-4325	99.49	72.20	1342
HSA-MIR-4688	99.48	64.68	828
HSA-MIR-6743-5P	99.48	63.60	721
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-3612	99.45	66.02	1333

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 34.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 11)

• REQ functions as an efficient adaptor protein between the SWI/SNF complex and RelB/p52 and plays important roles in noncanonical NF-kappaB transcriptional activation and its associated oncogenic activity. (PMID:20460684)
• found that targeting Requiem and Alg-2 did not result in extended culture viability, but resulted in an increase in maximum viable cell numbers and cumulative IVCD under fed-batch conditions (PMID:20571937)
• crystal structure of the C2H2-type zinc finger domain of human DPF2 with a canonical C2H2 fold, which contains two beta strands and one alpha helix, was reported. (PMID:21888896)
• DPF2 decreases monomeric and mono-ubiquitinated OCT4, assembles poly-ubiquitin chains on OCT4 mainly through Ub-K48 linkage (PMID:26417682)
• the role of SMARCA4 and the two SWI/SNF subunits SMARCD2/BAF60B and DPF2/BAF45D in leukaemia, was investigated. (PMID:26571505)
• The demonstrate that the histone acetylation-binding double PHD finger (DPF) domains of human MOZ (also known as KAT6A) and DPF2 (also known as BAF45d) accommodate a wide range of histone lysine acylation with the strongest preference for propionylation (Kcr). (PMID:27775714)
• Upon influenza virus infection, DPF2 dysregulated IFN-beta induction and expression of cytokines/chemokines and antiviral proteins. This study provides evidence that influenza virus utilizes DPF2 to escape host innate immunity. (PMID:28404846)
• Authors show that DPF2 interacts with the acetylated tails of both histones 3 and 4 via bipartite binding pockets on the DPF2 surface. Blocking these interactions through targeted mutagenesis of DPF2 abolishes its recruitment to target chromatin regions as well as its ability to prevent myeloid differentiation in vivo. (PMID:28533407)
• de novo variants in DPF2 cause Coffin-Siris syndrome and propose a dominant-negative mechanism of pathogenicity. (PMID:29429572)
• BAF45D knockdown decreases cell viability, inhibits colony formation, induces cell apoptosis and S-phase arrest in human pancreatic cancer cells. (PMID:32024442)
• DPF2-related Coffin-Siris syndrome type 7 in two generations. (PMID:38697389)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	dpf2	ENSDARG00000012219
danio_rerio	dpf2l	ENSDARG00000037291
mus_musculus	Dpf2	ENSMUSG00000024826
rattus_norvegicus	Dpf2	ENSRNOG00000020892
drosophila_melanogaster	tth	FBGN0030502
drosophila_melanogaster	d4	FBGN0033015
caenorhabditis_elegans		WBGENE00016200

Paralogs (9): DPF1 (ENSG00000011332), RSF1 (ENSG00000048649), KAT6A (ENSG00000083168), KAT8 (ENSG00000103510), PHF10 (ENSG00000130024), KAT7 (ENSG00000136504), KAT6B (ENSG00000156650), KAT5 (ENSG00000172977), DPF3 (ENSG00000205683)

Protein

Protein identifiers

Zinc finger protein ubi-d4 — Q92785 (reviewed: Q92785)

Alternative names: Apoptosis response zinc finger protein, BRG1-associated factor 45D, D4, zinc and double PHD fingers family 2, Protein requiem

All UniProt accessions (10): A0A994J3H5, A0A994J3P2, A0A994J414, A0A994J426, A0A994J6A8, A0A994J6N1, E9PN04, Q92785, H0YEI1, J3KMZ8

UniProt curated annotations — full annotation on UniProt →

Function. Plays an active role in transcriptional regulation by binding modified histones H3 and H4. Is a negative regulator of myeloid differentiation of hematopoietic progenitor cells. Might also have a role in the development and maturation of lymphoid cells. Involved in the regulation of non-canonical NF-kappa-B pathway.

Subunit / interactions. Interacts with the nucleosomes, in particular nucleosomes bearing histone H3 crotonylated at ‘Lys-14’ (H3K14cr) for which DPF2 has high affinity. Also interacts (via PHD-type zinc finger domains) with histone H3 butyrylated at ‘Lys-14’ (H3K14bu), histone H3 propionylated at ‘Lys-14’ (H3K14pr), and histone H3 acetylated at ‘Lys-14’ (H3K14ac). Interacts with histone H3 acetylated at ‘Lys-9’ (H3K9ac), histone H3 di-methylated at ‘Lys-9’ (H3K9me2), and histone H3 tri-methylated at ‘Lys-9’ (H3K9me3). Interacts with histone H4 acetylated at ‘Lys-12’ (H4K12ac). Interacts with histone H4 acetylated at ‘Lys-16’ (H4K16ac). Interacts with SWI/SNF complex components. Interacts with SMARCA2, SMARCA4, SMARCB1 and SMARCD1. Interacts with SMARCC1, SMARCC2 and ACTL6A. Interacts with RUNX1.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Ubiquitous.

Disease relevance. Coffin-Siris syndrome 7 (CSS7) [MIM:618027] A form of Coffin-Siris syndrome, a congenital multiple malformation syndrome with broad phenotypic and genetic variability. Cardinal features are intellectual disability, coarse facial features, hypertrichosis, and hypoplastic or absent fifth digit nails or phalanges. Additional features include malformations of the cardiac, gastrointestinal, genitourinary, and/or central nervous systems. Sucking/feeding difficulties, poor growth, ophthalmologic abnormalities, hearing impairment, and spinal anomalies are common findings. Both autosomal dominant and autosomal recessive inheritance patterns have been reported. CSS7 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the requiem/DPF family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q92785-1	1	yes
Q92785-2	2

RefSeq proteins (2): NP_001317237, NP_006259* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001965	Znf_PHD	Domain
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR013087	Znf_C2H2_type	Domain
IPR019787	Znf_PHD-finger	Domain
IPR025750	DPF1-3_N	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00628, PF14051

UniProt features (61 total): turn 11, strand 8, modified residue 7, cross-link 7, helix 7, sequence variant 5, compositionally biased region 4, zinc finger region 3, mutagenesis site 3, region of interest 3, initiator methionine 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
5VDC	X-RAY DIFFRACTION	1.6
3IUF	X-RAY DIFFRACTION	1.8
5B79	X-RAY DIFFRACTION	2.6
6LTH	ELECTRON MICROSCOPY	3
9RL4	ELECTRON MICROSCOPY	3.5
6LTJ	ELECTRON MICROSCOPY	3.7
9RN2	ELECTRON MICROSCOPY	4.1
9RMC	ELECTRON MICROSCOPY	4.2
9RN1	ELECTRON MICROSCOPY	5.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92785-F1	69.62	0.30

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (14): 2, 142, 172, 176, 200, 244, 280, 10, 99, 107, 108, 178, 196, 281

Mutagenesis-validated functional residues (3):

Position	Phenotype
275	strongly decreased interaction with histones h3 and h4 and loss of function; when associated with a-300 and a-346.
300	strongly decreased interaction with histones h3 and h4 and loss of function; when associated with a-275 and a-346.
346	strongly decreased interaction with histones h3 and h4 and loss of function; when associated with a-275 and a-300.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-9824585	Regulation of MITF-M-dependent genes involved in pigmentation
R-HSA-9845323	Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)
R-HSA-9933937	Formation of the canonical BAF (cBAF) complex
R-HSA-9933946	Formation of the embryonic stem cell BAF (esBAF) complex
R-HSA-9934037	Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)

MSigDB gene sets: 437 (showing top): GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_CHROMOSOME_ORGANIZATION, GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, LFA1_Q6, GOBP_CELL_CYCLE_PHASE_TRANSITION, chr11q13, CAGCTG_AP4_Q5, GOBP_REGULATION_OF_DNA_REPAIR, GOBP_NUCLEOTIDE_EXCISION_REPAIR, GCM_RING1, GOBP_NEGATIVE_REGULATION_OF_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, GOBP_APOPTOTIC_SIGNALING_PATHWAY, GOBP_REGULATION_OF_CHROMOSOME_SEGREGATION, MORF_CCNI, GCM_DPF2

GO Biological Process (14): negative regulation of transcription by RNA polymerase II (GO:0000122), chromatin remodeling (GO:0006338), regulation of transcription by RNA polymerase II (GO:0006357), apoptotic process (GO:0006915), nervous system development (GO:0007399), regulation of mitotic metaphase/anaphase transition (GO:0030071), regulation of G0 to G1 transition (GO:0070316), apoptotic signaling pathway (GO:0097190), positive regulation of stem cell population maintenance (GO:1902459), negative regulation of myeloid progenitor cell differentiation (GO:1905454), regulation of G1/S transition of mitotic cell cycle (GO:2000045), positive regulation of double-strand break repair (GO:2000781), regulation of nucleotide-excision repair (GO:2000819), chromatin organization (GO:0006325)

GO Molecular Function (6): transcription corepressor activity (GO:0003714), zinc ion binding (GO:0008270), histone H3K14ac reader activity (GO:0140015), histone H4K16ac reader activity (GO:0140046), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (8): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), centrosome (GO:0005813), cytosol (GO:0005829), SWI/SNF complex (GO:0016514), nBAF complex (GO:0071565), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
SWI/SNF chromatin remodelers	3
MITF-M-dependent gene expression	1
Regulation of endogenous retroelements	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
transcription by RNA polymerase II	2
negative regulation of DNA-templated transcription	2
regulation of mitotic cell cycle phase transition	2
SWI/SNF superfamily-type complex	2
regulation of transcription by RNA polymerase II	1
chromatin organization	1
regulation of DNA-templated transcription	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
system development	1
metaphase/anaphase transition of mitotic cell cycle	1
regulation of metaphase/anaphase transition of cell cycle	1
regulation of cell cycle process	1
G0 to G1 transition	1
apoptotic process	1
signal transduction	1
stem cell population maintenance	1
positive regulation of developmental process	1
positive regulation of multicellular organismal process	1
regulation of stem cell population maintenance	1
myeloid progenitor cell differentiation	1
negative regulation of hematopoietic progenitor cell differentiation	1
regulation of myeloid progenitor cell differentiation	1
G1/S transition of mitotic cell cycle	1
regulation of cell cycle G1/S phase transition	1
double-strand break repair	1
positive regulation of DNA repair	1
regulation of double-strand break repair	1
regulation of DNA repair	1
nucleotide-excision repair	1
cellular component organization	1
transcription coregulator activity	1
transition metal ion binding	1
histone H3 reader activity	1
histone H4 reader activity	1
binding	1
cation binding	1
chromosome	1

Protein interactions and networks

STRING

1084 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DPF2	ARID1A	O14497	989
DPF2	ARID1B	Q8NFD5	989
DPF2	SMARCD1	Q96GM5	973
DPF2	DPF1	Q92782	963
DPF2	ARID2	Q68CP9	929
DPF2	SMARCC1	Q92922	922
DPF2	SMARCE1	Q969G3	911
DPF2	SMARCA4	P51532	909
DPF2	PBRM1	Q86U86	906
DPF2	SMARCB1	Q12824	901
DPF2	BRD7	Q9NPI1	855
DPF2	DPF3	Q92784	847
DPF2	SMARCA2	P51531	844
DPF2	PHF10	Q8WUB8	834
DPF2	ACTL6A	O96019	822
DPF2	SMARCC2	Q8TAQ2	822

IntAct

203 interactions, top by confidence:

A	B	Type	Score
SMARCA4	ARID1A	psi-mi:“MI:0914”(association)	0.940
ARID1B	SMARCB1	psi-mi:“MI:0914”(association)	0.890
SMARCB1	ARID1A	psi-mi:“MI:0914”(association)	0.860
SMARCE1	ARID1A	psi-mi:“MI:0914”(association)	0.840
SMARCD1	ARID1A	psi-mi:“MI:0914”(association)	0.790
SMARCC1	ARID1A	psi-mi:“MI:0914”(association)	0.790
SMARCC2	ARID1A	psi-mi:“MI:0914”(association)	0.790
SMARCA4	SS18	psi-mi:“MI:0914”(association)	0.760
SS18	ARID1A	psi-mi:“MI:0914”(association)	0.760

BioGRID (521): LDOC1 (Two-hybrid), LNX1 (Two-hybrid), DPF2 (Affinity Capture-MS), DPF2 (Affinity Capture-MS), SMARCE1 (Affinity Capture-MS), ARID1A (Affinity Capture-MS), ARID1B (Affinity Capture-MS), SMARCC2 (Affinity Capture-MS), SMARCC1 (Affinity Capture-MS), SMARCA2 (Affinity Capture-MS), SMARCA4 (Affinity Capture-MS), SMARCD3 (Affinity Capture-MS), SMARCD2 (Affinity Capture-MS), SMARCD1 (Affinity Capture-MS), SMARCB1 (Affinity Capture-MS)

ESM2 similar proteins: A0A286Y9D1, A0JMK9, A2BIL7, A8DZJ1, B2KF05, B2RRD7, B4KLY7, F4IDY7, O15042, O94880, O97159, P55201, P97496, Q05913, Q20448, Q2T9V9, Q3T095, Q4V7A6, Q5EA28, Q5R7X2, Q61103, Q63ZP1, Q6DD45, Q6FSB1, Q6GQJ2, Q6IE81, Q6IE82, Q6NV83, Q6NWE1, Q6P2L6, Q6ZPI0, Q7KRW8, Q7ZVP1, Q803A0, Q8BRB7, Q8WML3, Q8WUB8, Q92613, Q92785, Q92922

Diamond homologs: A0A1W2PPD8, A1A5Q5, A1YVX4, A2A8L1, A2AUY4, A2BIL7, A6H619, A8DZJ1, A9LMC0, B2RXH2, B7ZS37, B9RU15, C0SUT9, D3ZD32, F4I240, F4I6G4, F4KIX0, O16102, O43918, O64752, O75164, O88379, O94953, O97159, P29375, P39956, P41228, P41229, P41230, P56163, P58268, P58269, P58270, Q03833, Q09477, Q10RP4, Q12873, Q14839, Q22516, Q23541

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
DPF2	“up-regulates activity”	“SWI/SNF complex”	binding
DPF2	“up-regulates activity”	NfKb-p65/p50	binding
DPF2	“down-regulates activity”	RUNX1	binding
DPF2	down-regulates	Differentiation
DPF2	“down-regulates activity”	ESRRA	binding
DPF2	“form complex”	“Embryonic stem cell-specific SWI/SNF”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 150 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Formation of the canonical BAF (cBAF) complex	15	93.3×	1e-26
Formation of the non-canonical BAF (ncBAF) complex	12	79.0×	6e-20
Formation of the embryonic stem cell BAF (esBAF) complex	13	76.6×	3e-21
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	17	76.1×	2e-27
Formation of the polybromo-BAF (pBAF) complex	12	74.6×	2e-19
Regulation of endogenous retroelements	15	54.2×	2e-21
Regulation of MITF-M-dependent genes involved in pigmentation	19	49.5×	3e-26
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	11	32.4×	7e-13

GO biological processes:

GO term	Partners	Fold	FDR
regulation of G0 to G1 transition	15	77.2×	1e-23
regulation of nucleotide-excision repair	15	68.9×	9e-23
regulation of mitotic metaphase/anaphase transition	15	56.8×	3e-21
nucleosome disassembly	9	55.1×	2e-12
positive regulation of T cell differentiation	13	45.2×	8e-17
positive regulation of double-strand break repair	15	39.4×	2e-18
positive regulation of myoblast differentiation	13	36.4×	2e-15
regulation of G1/S transition of mitotic cell cycle	15	35.1×	1e-17

Disease & clinical

Clinical variants and AI predictions

ClinVar

274 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	10
Uncertain significance	106
Likely benign	109
Benign	13

Top pathogenic / likely-pathogenic (17)

Variant ID	HGVS	Classification
1173064	NM_006268.5(DPF2):c.1066T>G (p.Cys356Gly)	Pathogenic
1201633	NM_006268.5(DPF2):c.1045G>A (p.Asp349Asn)	Pathogenic
438643	NM_006268.5(DPF2):c.827G>T (p.Cys276Phe)	Pathogenic
545683	NM_006268.5(DPF2):c.990C>G (p.Cys330Trp)	Pathogenic
545685	NM_006268.5(DPF2):c.1037A>G (p.Asp346Gly)	Pathogenic
545686	NM_006268.5(DPF2):c.1099+1G>A	Pathogenic
985019	NM_006268.5(DPF2):c.904+1G>A	Pathogenic
1198043	NM_006268.5(DPF2):c.964T>C (p.Trp322Arg)	Likely pathogenic
1200174	NM_006268.5(DPF2):c.1036G>A (p.Asp346Asn)	Likely pathogenic
1676450	NM_006268.5(DPF2):c.1099+2dup	Likely pathogenic
1805984	NM_006268.5(DPF2):c.1067G>C (p.Cys356Ser)	Likely pathogenic
2442163	NM_006268.5(DPF2):c.1094dup (p.Pro365_Glu366insTer)	Likely pathogenic
3064790	NM_006268.5(DPF2):c.970T>G (p.Cys324Gly)	Likely pathogenic
3376275	NM_006268.5(DPF2):c.899G>T (p.Arg300Leu)	Likely pathogenic
3769178	NM_006268.5(DPF2):c.976G>A (p.Glu326Lys)	Likely pathogenic
545684	NM_006268.5(DPF2):c.1049G>A (p.Arg350His)	Likely pathogenic
986144	NM_006268.5(DPF2):c.1033T>G (p.Cys345Gly)	Likely pathogenic

SpliceAI

1404 predictions. Top by Δscore:

Variant	Effect	Δscore
11:65333883:G:T	donor_gain	1.0000
11:65333916:GCT:G	donor_gain	1.0000
11:65333919:G:GG	donor_gain	1.0000
11:65340380:TGCA:T	acceptor_loss	1.0000
11:65340381:GCAG:G	acceptor_loss	1.0000
11:65340382:CAGC:C	acceptor_loss	1.0000
11:65340383:A:AG	acceptor_gain	1.0000
11:65340383:A:AT	acceptor_loss	1.0000
11:65340384:G:GG	acceptor_gain	1.0000
11:65340384:G:GT	acceptor_loss	1.0000
11:65340384:GC:G	acceptor_gain	1.0000
11:65340384:GCC:G	acceptor_gain	1.0000
11:65340384:GCCT:G	acceptor_gain	1.0000
11:65340384:GCCTT:G	acceptor_gain	1.0000
11:65340541:TCC:T	donor_gain	1.0000
11:65340541:TCCAG:T	donor_loss	1.0000
11:65340542:CCAGG:C	donor_loss	1.0000
11:65340543:CAGGT:C	donor_loss	1.0000
11:65340547:T:G	donor_loss	1.0000
11:65340958:T:TA	acceptor_gain	1.0000
11:65340961:CACAG:C	acceptor_loss	1.0000
11:65340962:ACAG:A	acceptor_gain	1.0000
11:65340963:C:G	acceptor_gain	1.0000
11:65340963:CAGG:C	acceptor_loss	1.0000
11:65340964:A:AG	acceptor_gain	1.0000
11:65340964:AG:A	acceptor_gain	1.0000
11:65340965:G:GA	acceptor_gain	1.0000
11:65340965:GG:G	acceptor_gain	1.0000
11:65340965:GGA:G	acceptor_gain	1.0000
11:65340965:GGAT:G	acceptor_gain	1.0000

AlphaMissense

2563 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:65340410:G:C	A20P	1.000
11:65340422:T:C	C24R	1.000
11:65340436:T:A	N28K	1.000
11:65340436:T:G	N28K	1.000
11:65340441:G:C	R30P	1.000
11:65340444:T:C	L31P	1.000
11:65340455:C:A	R35S	1.000
11:65340456:G:C	R35P	1.000
11:65340471:C:A	P40H	1.000
11:65340473:T:C	F41L	1.000
11:65340475:C:A	F41L	1.000
11:65340475:C:G	F41L	1.000
11:65340480:A:G	D43G	1.000
11:65340480:A:T	D43V	1.000
11:65340489:C:T	T46I	1.000
11:65340498:C:A	A49D	1.000
11:65340501:A:C	Q50P	1.000
11:65340518:T:A	W56R	1.000
11:65340518:T:C	W56R	1.000
11:65340992:T:G	Y74D	1.000
11:65341007:T:A	W79R	1.000
11:65341007:T:C	W79R	1.000
11:65341008:G:C	W79S	1.000
11:65341009:G:C	W79C	1.000
11:65341009:G:T	W79C	1.000
11:65344063:T:A	C211S	1.000
11:65344063:T:C	C211R	1.000
11:65344064:G:A	C211Y	1.000
11:65344064:G:C	C211S	1.000
11:65344064:G:T	C211F	1.000

dbSNP variants (sampled 300 via entrez): RS1000077930 (11:65341010 C>T), RS1000323963 (11:65334903 G>A), RS1000392770 (11:65354482 G>C), RS1000446606 (11:65354577 TC>T), RS1000657096 (11:65333735 G>A), RS1000771548 (11:65333853 G>A,C), RS1000872657 (11:65342335 AG>A), RS1000997866 (11:65340228 G>A), RS1001125483 (11:65346768 G>T), RS1001214281 (11:65347416 C>T), RS1001418266 (11:65335039 A>G), RS1001724500 (11:65348510 G>A), RS1001776988 (11:65348827 C>T), RS1002271843 (11:65334535 A>G), RS1002315030 (11:65347805 G>A,T)

Disease associations

OMIM: gene MIM:601671 | disease phenotypes: MIM:618027, MIM:135900, MIM:609943, MIM:614562

GenCC curated gene-disease

Disease	Classification	Inheritance
Coffin-Siris syndrome 7	Strong	Autosomal dominant
Coffin-Siris syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Coffin-Siris syndrome	Definitive	AD

Mondo (4): Coffin-Siris syndrome 7 (MONDO:0054831), autism spectrum disorder (MONDO:0005258), Coffin-Siris syndrome (MONDO:0015452), Coffin-Siris syndrome 1 (MONDO:0007617)

Orphanet (2): Coffin-Siris syndrome (Orphanet:1465), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

103 total (30 of 103 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000085	Horseshoe kidney
HP:0000119	Abnormality of the genitourinary system
HP:0000154	Wide mouth
HP:0000179	Thick lower lip vermilion
HP:0000219	Thin upper lip vermilion
HP:0000243	Trigonocephaly
HP:0000252	Microcephaly
HP:0000280	Coarse facial features
HP:0000286	Epicanthus
HP:0000289	Broad philtrum
HP:0000294	Low anterior hairline
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000400	Macrotia
HP:0000403	Recurrent otitis media
HP:0000444	Convex nasal ridge
HP:0000445	Wide nose
HP:0000455	Broad nasal tip
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000505	Visual impairment
HP:0000508	Ptosis
HP:0000540	Hypermetropia

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002481_8	Acne (severe)	3.000000e-11
GCST008972_84	Urate levels	2.000000e-09
GCST90002397_529	Mean spheric corpuscular volume	8.000000e-16

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536436	Coffin-Siris syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

33 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, affects cotreatment, increases abundance, increases expression	2
Valproic Acid	decreases expression, affects expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
N-(1,3-dimethylbutyl)-N’-phenyl-p-phenylenediamine quinone	affects expression	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases expression, increases abundance, affects cotreatment	1
bisphenol A	increases expression	1
salinomycin	decreases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
coumarin	affects phosphorylation	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
JP8 aviation fuel	decreases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
Acetaminophen	increases expression	1
Acrolein	affects cotreatment, increases expression, increases abundance	1
Caffeine	decreases phosphorylation	1
Cocaine	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Menthol	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Ozone	increases expression, increases abundance, affects cotreatment	1
Quercetin	decreases phosphorylation	1
Urethane	increases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1C2	Abcam A-431 DPF2 KO	Cancer cell line	Female
CVCL_SL11	HAP1 DPF2 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	PHASE3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	PHASE3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	PHASE3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	PHASE3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	PHASE3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT06229210	PHASE3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder