PHF2

Summary

PHF2 (PHD finger protein 2, HGNC:8920) is a protein-coding gene on chromosome 9q22.31, encoding Lysine-specific demethylase PHF2 (O75151). Lysine demethylase that demethylates both histones and non-histone proteins.

This gene encodes a protein which contains a zinc finger-like PHD (plant homeodomain) finger, distinct from other classes of zinc finger motifs, and a hydrophobic and highly conserved domain. The PHD finger shows the typical Cys4-His-Cys3 arrangement. PHD finger genes are thought to belong to a diverse group of transcriptional regulators possibly affecting eukaryotic gene expression by influencing chromatin structure.

Source: NCBI Gene 5253 — RefSeq curated summary.

At a glance

• GWAS associations: 19
• Clinical variants (ClinVar): 182 total — 1 likely-pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_005392

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8920
Approved symbol	PHF2
Name	PHD finger protein 2
Location	9q22.31
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0662, JHDM1E, CENP-35, KDM7C
Ensembl gene	ENSG00000197724
Ensembl biotype	protein_coding
OMIM	604351
Entrez	5253

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000359246, ENST00000610682, ENST00000851896, ENST00000851897, ENST00000851898, ENST00000851899, ENST00000937581, ENST00000942581

RefSeq mRNA: 1 — MANE Select: NM_005392 NM_005392

CCDS: CCDS35069

Canonical transcript exons

ENST00000359246 — 22 exons

Exon	Start	End
ENSE00000900718	93676594	93676963
ENSE00000900722	93675680	93675789
ENSE00000900724	93674927	93675022
ENSE00000900726	93673585	93673862
ENSE00000900727	93667080	93667240
ENSE00000900733	93663517	93663635
ENSE00000900738	93662907	93663026
ENSE00000900740	93660192	93660560
ENSE00000900745	93659511	93659600
ENSE00000900746	93658145	93658236
ENSE00000900747	93656489	93656595
ENSE00000900749	93654413	93654575
ENSE00000900750	93653179	93653365
ENSE00000900751	93649071	93649212
ENSE00000900752	93645629	93645789
ENSE00000900753	93636411	93636525
ENSE00001031830	93629970	93630055
ENSE00001293646	93677588	93679587
ENSE00001623198	93665686	93665864
ENSE00001657273	93665990	93666060
ENSE00001688811	93655934	93656021
ENSE00001883160	93576584	93576871

Expression profiles

Bgee: expression breadth ubiquitous, 271 present calls, max score 92.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.9236 / max 117.1020, expressed in 1785 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
97432	3.4060	1499
97431	3.0910	1144
97430	2.3058	1327
97433	2.2341	1291
97429	0.8783	514
97435	0.0051	4
97436	0.0034	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	92.74	gold quality
ventricular zone	UBERON:0003053	92.50	gold quality
cortical plate	UBERON:0005343	92.02	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.89	gold quality
endometrium epithelium	UBERON:0004811	91.73	gold quality
cerebellar hemisphere	UBERON:0002245	91.70	gold quality
cerebellar cortex	UBERON:0002129	91.67	gold quality
cerebellar vermis	UBERON:0004720	91.61	gold quality
cerebellum	UBERON:0002037	91.02	gold quality
tendon of biceps brachii	UBERON:0008188	90.99	gold quality
medial globus pallidus	UBERON:0002477	90.88	gold quality
body of uterus	UBERON:0009853	90.69	gold quality
adenohypophysis	UBERON:0002196	90.31	gold quality
left ovary	UBERON:0002119	90.19	gold quality
endocervix	UBERON:0000458	90.15	gold quality
right ovary	UBERON:0002118	90.09	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	89.91	gold quality
muscle layer of sigmoid colon	UBERON:0035805	89.76	gold quality
lower esophagus muscularis layer	UBERON:0035833	89.68	gold quality
lower esophagus	UBERON:0013473	89.66	gold quality
tibial nerve	UBERON:0001323	89.59	gold quality
pituitary gland	UBERON:0000007	89.53	gold quality
ovary	UBERON:0000992	89.52	gold quality
left uterine tube	UBERON:0001303	89.45	gold quality
right lung	UBERON:0002167	89.41	gold quality
apex of heart	UBERON:0002098	89.32	gold quality
mucosa of stomach	UBERON:0001199	89.25	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	89.23	gold quality
ectocervix	UBERON:0012249	89.06	gold quality
globus pallidus	UBERON:0001875	89.04	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.42
E-GEOD-111727	no	244.60

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ARID5B

miRNA regulators (miRDB)

140 targeting PHF2, 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-5692A	100.00	74.40	6850
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-4267	99.96	66.53	2368
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-300	99.92	71.76	2856

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 16)

• Differential association of alterations in FANCC and PTCH1 with that of PHF2, XPA and two breast cancer susceptibility genes (BRCA1/BRCA2) in the two age groups suggests differences in their molecular pathogenesis. (PMID:18990233)
• the crystal structures of PHF2 Jumonji domain in the absence and presence of additional exogenous metal ions were determined. (PMID:21167174)
• JARID1B and PHF2 are overexpressed in esophageal squamous cell carcinoma (ESCC) and they may play crucial roles in the course of ESCC initiation and/or progression (PMID:22534467)
• PHF2 acts as a tumor suppressor in association with p53 in cancer development and ensures p53-mediated cell death in response to chemotherapy. (PMID:25043306)
• PHF2 is likely to repress rDNA transcription by competing with PHF8 for binding of ribosomal DNA promoter and by recruiting H3K9me2/3 methyltransferase SUV39H1. (PMID:25204660)
• Frameshift mutations of PHF2 may play a role in tumorigenesis through its TSG inactivation in CRC and GC. (PMID:27744626)
• Our results demonstrate that the IKAROS promotes PHF2 expression, and suggest that PHF2 (low) expression works with the IKAROS gene deletion to drive oncogenesis of ALL (PMID:28994305)
• PHF2 is a negative epigenetic regulator of MK and erythroid differentiation. (PMID:29336484)
• lower expression of PHF2 promoted hepatocellular carcinoma (HCC) cell migration and linked to worse overall survival in HCC patients. Finally, the negative correlation between miR-221 and PHF2 expression levels in HCC specimens was further confirmed. (PMID:31214616)
• The HCF-1:ChREBP complex resides at lipogenic gene promoters, where HCF-1 regulates H3K4 trimethylation to prime recruitment of the Jumonji C domain-containing histone demethylase PHF2 for epigenetic activation of these promoters.. these findings define HCF-1’s interaction with ChREBP as a previously unappreciated mechanism whereby glucose signals are both relayed to ChREBP and transmitted for epigenetic regulation (PMID:31227231)
• PHF2 regulates homology-directed DNA repair by controlling the resection of DNA double strand breaks. (PMID:32232336)
• Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders. (PMID:34741163)
• HIF-1alpha-mediated augmentation of miRNA-18b-5p facilitates proliferation and metastasis in osteosarcoma through attenuation PHF2. (PMID:35729160)
• Circ_MBNL3 Restrains Hepatocellular Carcinoma Progression by Sponging miR-873-5p to Release PHF2. (PMID:36380035)
• Palmitoylation-driven PHF2 ubiquitination remodels lipid metabolism through the SREBP1c axis in hepatocellular carcinoma. (PMID:37828054)
• PHF2-mediated H3K9me balance orchestrates heterochromatin stability and neural progenitor proliferation. (PMID:38890452)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	phf2	ENSDARG00000018691
mus_musculus	Phf2	ENSMUSG00000038025
rattus_norvegicus	Phf2	ENSRNOG00000016816
drosophila_melanogaster	Kdm2	FBGN0037659
caenorhabditis_elegans		WBGENE00005013
caenorhabditis_elegans		WBGENE00017920
caenorhabditis_elegans		WBGENE00020821

Paralogs (4): KDM7A (ENSG00000006459), KDM2B (ENSG00000089094), PHF8 (ENSG00000172943), KDM2A (ENSG00000173120)

Protein

Protein identifiers

Lysine-specific demethylase PHF2 — O75151 (reviewed: O75151)

Alternative names: GRC5, PHD finger protein 2

All UniProt accessions (2): A0A087WW48, O75151

UniProt curated annotations — full annotation on UniProt →

Function. Lysine demethylase that demethylates both histones and non-histone proteins. Enzymatically inactive by itself, and becomes active following phosphorylation by PKA: forms a complex with ARID5B and mediates demethylation of methylated ARID5B. Demethylation of ARID5B leads to target the PHF2-ARID5B complex to target promoters, where PHF2 mediates demethylation of dimethylated ‘Lys-9’ of histone H3 (H3K9me2), followed by transcription activation of target genes. The PHF2-ARID5B complex acts as a coactivator of HNF4A in liver. PHF2 is recruited to trimethylated ‘Lys-4’ of histone H3 (H3K4me3) at rDNA promoters and promotes expression of rDNA. Involved in the activation of toll-like receptor 4 (TLR4)-target inflammatory genes in macrophages by catalyzing the demethylation of trimethylated histone H4 lysine 20 (H4K20me3) at the gene promoters.

Subunit / interactions. Component of the PHF2-ARID5B complex, at least composed of PHF2 and ARID5B. Interacts with HNF4A and NR1H4. Interacts with RELA.

Subcellular location. Nucleus. Nucleolus. Chromosome. Centromere. Kinetochore.

Tissue specificity. Widely expressed, including in liver (at protein level).

Post-translational modifications. Phosphorylated by PKA on specific serine residues, leading to the formation of an active lysine demethylase complex.

Activity regulation. Enzymatically inactive by itself, and become active following phosphorylation by PKA.

Domain organisation. The PHD-type zinc finger mediates the binding to H3K4me2 and H3K4me3.

Similarity. Belongs to the JHDM1 histone demethylase family. JHDM1D subfamily.

RefSeq proteins (1): NP_005383* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001965	Znf_PHD	Domain
IPR003347	JmjC_dom	Domain
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR019786	Zinc_finger_PHD-type_CS	Conserved_site
IPR019787	Znf_PHD-finger	Domain
IPR041070	JHD	Domain
IPR050690	JHDM1_Histone_Demethylase	Family

Pfam: PF00628, PF02373, PF17811

Catalyzed reactions (Rhea), 1 shown:

• N(6),N(6)-dimethyl-L-lysyl(9)-[histone H3] + 2-oxoglutarate + O2 = N(6)-methyl-L-lysyl(9)-[histone H3] + formaldehyde + succinate + CO2 (RHEA:60192)

UniProt features (135 total): sequence conflict 36, helix 23, strand 17, modified residue 16, compositionally biased region 10, binding site 9, mutagenesis site 8, turn 5, region of interest 5, sequence variant 2, chain 1, domain 1, zinc finger region 1, cross-link 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
7M10	X-RAY DIFFRACTION	1.15
3KQI	X-RAY DIFFRACTION	1.78
3PUA	X-RAY DIFFRACTION	1.89
3PU8	X-RAY DIFFRACTION	1.94
3PU3	X-RAY DIFFRACTION	1.95
3PTR	X-RAY DIFFRACTION	1.95
3PUS	X-RAY DIFFRACTION	2.08
8F8Y	X-RAY DIFFRACTION	3.06
8F8Z	X-RAY DIFFRACTION	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75151-F1	62.14	0.34

Functional residue map

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

Ligand- & substrate-binding residues (9): 193; 246; 249; 251; 259; 266; 321; 321; 323

Post-translational modifications (17): 474, 479, 539, 655, 681, 705, 720, 728, 730, 733, 734, 738, 879, 882, 899, 1056, 711

Mutagenesis-validated functional residues (8):

Position	Phenotype
7	abolishes binding to h3k4me2 and h3k4me3.
29	abolishes binding to h3k4me2 and h3k4me3.
249	abolishes demethylase activity.
321	does not alter iron-binding nor activates histone demethylase activity.
757	abolishes phosphorylation by pka and activation of demethylase activity; when associated with a-899; a-954 and a-1056.
899	abolishes phosphorylation by pka and activation of demethylase activity; when associated with a-757; a-954 and a-1056.
954	abolishes phosphorylation by pka and activation of demethylase activity; when associated with a-757; a-899 and a-1056.
1056	abolishes phosphorylation by pka and activation of demethylase activity; when associated with a-757; a-899 and a-954.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-3214842	HDMs demethylate histones

MSigDB gene sets: 178 (showing top): GCACCTT_MIR18A_MIR18B, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GCM_GSPT1, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, TTTGTAG_MIR520D, GCM_ZNF198, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_DN, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, GCM_BCL2L1, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_DEMETHYLATION, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, GOBP_NUCLEUS_ORGANIZATION

GO Biological Process (8): liver development (GO:0001889), chromatin remodeling (GO:0006338), regulation of transcription by RNA polymerase II (GO:0006357), protein demethylation (GO:0006482), transcription initiation-coupled chromatin remodeling (GO:0045815), negative regulation of rDNA heterochromatin formation (GO:0061188), chromatin organization (GO:0006325), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (12): transcription coregulator activity (GO:0003712), transcription coactivator activity (GO:0003713), iron ion binding (GO:0005506), zinc ion binding (GO:0008270), histone demethylase activity (GO:0032452), histone H3K9 demethylase activity (GO:0032454), histone H4K20 demethylase activity (GO:0035575), histone H3K4me3 reader activity (GO:0140002), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), metal ion binding (GO:0046872), dioxygenase activity (GO:0051213)

GO Cellular Component (6): kinetochore (GO:0000776), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), chromosome, centromeric region (GO:0000775), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Chromatin modifying enzymes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membraneless organelle	3
regulation of DNA-templated transcription	2
transition metal ion binding	2
nuclear lumen	2
gland development	1
hepaticobiliary system development	1
chromatin organization	1
transcription by RNA polymerase II	1
protein dealkylation	1
demethylation	1
transcription initiation at RNA polymerase II promoter	1
positive regulation of gene expression, epigenetic	1
rDNA heterochromatin formation	1
negative regulation of heterochromatin formation	1
regulation of rDNA heterochromatin formation	1
cellular component organization	1
DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
transcription regulator activity	1
transcription coregulator activity	1
positive regulation of DNA-templated transcription	1
protein demethylase activity	1
histone modifying activity	1
histone H3 demethylase activity	1
2-oxoglutarate-dependent dioxygenase activity	1
histone H4 demethylase activity	1
histone H3 reader activity	1
binding	1
catalytic activity	1
cation binding	1
oxidoreductase activity	1
condensed chromosome, centromeric region	1
supramolecular complex	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1
chromosomal region	1

Protein interactions and networks

STRING

1257 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PHF2	ARID5B	Q14865	774
PHF2	NMD3	Q96D46	546
PHF2	KDM4D	Q6B0I6	527
PHF2	KDM4A	O75164	524
PHF2	KDM4B	O94953	486
PHF2	KDM3A	Q9Y4C1	478
PHF2	KDM5A	P29375	471
PHF2	JMJD1C	Q15652	455
PHF2	KDM4E	B2RXH2	454
PHF2	KDM6B	O15054	453
PHF2	KDM3B	Q7LBC6	444
PHF2	KDM5C	P41229	441
PHF2	KDM5B	Q9UGL1	440
PHF2	KDM1A	O60341	430
PHF2	KDM4C	Q9H3R0	419

IntAct

36 interactions, top by confidence:

A	B	Type	Score
PHF2	H2BC21	psi-mi:“MI:0915”(physical association)	0.560
SUPT5H	POLR2D	psi-mi:“MI:0914”(association)	0.530
NR1H4	PHF2	psi-mi:“MI:0914”(association)	0.520
NR1H4	PHF2	psi-mi:“MI:0407”(direct interaction)	0.520
HNF4A	PHF2	psi-mi:“MI:0407”(direct interaction)	0.440
ARID5B	PHF2	psi-mi:“MI:0407”(direct interaction)	0.440
PHF2	CPNE3	psi-mi:“MI:0915”(physical association)	0.400
Kifc5b	KPNA3	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CSNK2B	OSBPL8	psi-mi:“MI:0914”(association)	0.350
H2AZ1	SUPT5H	psi-mi:“MI:0914”(association)	0.350
H2BC21	SMCHD1	psi-mi:“MI:0914”(association)	0.350
SSRP1	DDX39A	psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
VPS37A	PHF2	psi-mi:“MI:0914”(association)	0.350
PHF8	PHF2	psi-mi:“MI:0914”(association)	0.350
USP20	MYO9A	psi-mi:“MI:0914”(association)	0.350
H2BC10	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
CDC14B	PES1	psi-mi:“MI:2364”(proximity)	0.270
LHX2	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
AGGF1	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
DDX52	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
FASTKD2	MED19	psi-mi:“MI:2364”(proximity)	0.270
NOLC1	ILVBL	psi-mi:“MI:2364”(proximity)	0.270
PPIL4	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
SF3B4	MED19	psi-mi:“MI:2364”(proximity)	0.270
SMNDC1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
ZC3H11A	ESYT2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (143): PHF2 (Proximity Label-MS), PHF2 (Affinity Capture-MS), PHF2 (Proximity Label-MS), PHF2 (Proximity Label-MS), PHF2 (Affinity Capture-MS), PHF2 (Affinity Capture-RNA), PHF2 (Negative Genetic), PRMT5 (Negative Genetic), PHF2 (Synthetic Growth Defect), PHF2 (Affinity Capture-RNA), PHF2 (Affinity Capture-MS), PHF2 (Affinity Capture-MS), PHF2 (Affinity Capture-RNA), PHF2 (Affinity Capture-MS), PHF2 (Affinity Capture-MS)

ESM2 similar proteins: A0A088MLT8, A0A0G2K0D3, A2AQ19, B3KU38, D3ZTQ1, E1BTG2, E6ZGB4, E9PSK7, O35274, O60271, O75151, O75376, P12755, P22682, P29536, P49140, Q08DA0, Q13191, Q3B7T9, Q3TTA7, Q3UHZ5, Q3USH5, Q3YEC7, Q4KKX4, Q58A65, Q5SFM8, Q5U3K5, Q60698, Q60974, Q62415, Q640N2, Q6P5Q4, Q6R891, Q70E73, Q80XA6, Q86YP4, Q8BVA4, Q8CHY6, Q8K4S7, Q8R3Y5

Diamond homologs: A2WXR5, A2XTW9, A2Y0Q2, A2Y4R8, B8ADZ3, B8AMA8, B8B8C5, B8B8I3, B8BJV8, E6ZGB4, F4JL28, O75151, O81488, P0CH95, Q12830, Q2R837, Q40359, Q5XEM9, Q60DW3, Q6BER5, Q6BXJ4, Q6P949, Q6YTY3, Q6Z7F4, Q75IR6, Q7F2Z1, Q7XUW3, Q80TJ7, Q84TV4, Q8C9B9, Q8H383, Q8LA16, Q8S8M9, Q9BTC0, Q9FFF5, Q9M2B4, Q9SRM4, Q9UPP1, Q9W0T1, Q9W352

SIGNOR signaling

14 interactions.

A	Effect	B	Mechanism
PKA	“up-regulates activity”	PHF2	phosphorylation
PHF2	“up-regulates activity”	ARID5B	binding
ARID5B	“up-regulates activity”	PHF2	binding
PHF2	“up-regulates activity”	H3C1	demethylation
PHF2	“up-regulates activity”	H3-4	demethylation
PHF2	“up-regulates activity”	H3-3A	demethylation
PHF2	“down-regulates activity”	H3-3A	demethylation
PHF2	“down-regulates activity”	H3-4	demethylation
PHF2	“down-regulates activity”	H3C1	demethylation
PHF2	“down-regulates activity”	“Histone H3”	demethylation
2-oxoglutarate(2-)	“up-regulates activity”	PHF2	“chemical activation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 45 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
CHD1 and CHD2 subfamily	5	14.7×	5e-03
Dengue Virus-Host Interactions	6	7.4×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	123
Likely benign	19
Benign	15

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1676525	NM_005392.4(PHF2):c.2749C>T (p.Gln917Ter)	Likely pathogenic

SpliceAI

4557 predictions. Top by Δscore:

Variant	Effect	Δscore
9:93629968:A:AG	acceptor_gain	1.0000
9:93629969:G:GA	acceptor_gain	1.0000
9:93629969:GCT:G	acceptor_gain	1.0000
9:93629969:GCTGT:G	acceptor_gain	1.0000
9:93630056:G:GG	donor_gain	1.0000
9:93636409:A:AG	acceptor_gain	1.0000
9:93636410:G:GC	acceptor_gain	1.0000
9:93636410:GT:G	acceptor_gain	1.0000
9:93636410:GTAAA:G	acceptor_gain	1.0000
9:93636524:AGG:A	donor_loss	1.0000
9:93636525:GG:G	donor_loss	1.0000
9:93636526:G:C	donor_loss	1.0000
9:93645624:TGCA:T	acceptor_loss	1.0000
9:93645625:GCAGT:G	acceptor_loss	1.0000
9:93645627:A:AG	acceptor_gain	1.0000
9:93645627:A:T	acceptor_loss	1.0000
9:93645627:AGT:A	acceptor_gain	1.0000
9:93645628:G:GT	acceptor_gain	1.0000
9:93645628:GT:G	acceptor_gain	1.0000
9:93645628:GTG:G	acceptor_gain	1.0000
9:93645628:GTGCT:G	acceptor_gain	1.0000
9:93645785:CGTGG:C	donor_loss	1.0000
9:93645786:GTGG:G	donor_gain	1.0000
9:93645788:GG:G	donor_gain	1.0000
9:93645789:GG:G	donor_gain	1.0000
9:93645790:G:GG	donor_gain	1.0000
9:93645790:GT:G	donor_loss	1.0000
9:93645791:T:A	donor_loss	1.0000
9:93649067:CTA:C	acceptor_loss	1.0000
9:93649068:TA:T	acceptor_loss	1.0000

AlphaMissense

7188 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:93576795:T:C	C8R	1.000
9:93576796:G:A	C8Y	1.000
9:93576797:C:G	C8W	1.000
9:93576801:T:C	C10R	1.000
9:93576828:T:C	F19L	1.000
9:93576830:C:A	F19L	1.000
9:93576830:C:G	F19L	1.000
9:93576832:T:C	M20T	1.000
9:93576835:T:A	I21N	1.000
9:93576835:T:G	I21S	1.000
9:93576840:T:A	C23S	1.000
9:93576840:T:C	C23R	1.000
9:93576841:G:A	C23Y	1.000
9:93576841:G:C	C23S	1.000
9:93576841:G:T	C23F	1.000
9:93576842:C:G	C23W	1.000
9:93576849:T:A	C26S	1.000
9:93576849:T:C	C26R	1.000
9:93576850:G:A	C26Y	1.000
9:93576850:G:C	C26S	1.000
9:93576851:C:G	C26W	1.000
9:93576858:T:A	W29R	1.000
9:93576858:T:C	W29R	1.000
9:93576860:G:C	W29C	1.000
9:93576860:G:T	W29C	1.000
9:93576861:T:C	F30L	1.000
9:93576862:T:C	F30S	1.000
9:93576862:T:G	F30C	1.000
9:93576863:C:A	F30L	1.000
9:93576863:C:G	F30L	1.000

dbSNP variants (sampled 300 via entrez): RS1000095901 (9:93579686 G>C), RS1000111733 (9:93678873 A>T), RS1000163363 (9:93578411 G>A,T), RS1000164269 (9:93583983 C>T), RS1000172004 (9:93653631 A>C,G), RS1000216082 (9:93584216 T>C), RS1000217030 (9:93651563 C>G), RS1000266446 (9:93641029 T>C), RS1000274037 (9:93614301 G>T), RS1000278656 (9:93646056 G>A), RS1000289187 (9:93670037 C>T), RS1000308402 (9:93578392 C>G,T), RS1000374568 (9:93591921 G>A,C), RS1000426900 (9:93579914 C>G), RS1000445732 (9:93657013 G>A,T)

Disease associations

OMIM: gene MIM:604351 | disease phenotypes:

GenCC curated gene-disease

Mondo (3): prostate cancer (MONDO:0008315), autism spectrum disorder (MONDO:0005258), neurodevelopmental disorder (MONDO:0700092)

Orphanet (2): Familial prostate cancer (Orphanet:1331), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST005316_404	Intelligence (MTAG)	2.000000e-08
GCST005316_60	Intelligence (MTAG)	9.000000e-09
GCST006288_481	Heel bone mineral density	4.000000e-08
GCST006288_617	Heel bone mineral density	3.000000e-17
GCST006288_740	Heel bone mineral density	3.000000e-10
GCST006919_2	Ability to confide in someone	2.000000e-09
GCST006923_6	Loneliness	7.000000e-11
GCST006924_2	Loneliness (MTAG)	1.000000e-13
GCST006979_361	Heel bone mineral density	5.000000e-31
GCST007387_7	Insomnia symptoms (never/rarely vs. sometimes/usually)	2.000000e-08
GCST007388_46	Insomnia symptoms (never/rarely vs. usually)	7.000000e-12
GCST009463_4	Loneliness	2.000000e-11
GCST010988_398	Adult body size	5.000000e-13
GCST011768_6	Schizophrenia	4.000000e-09
GCST012043_6	Childhood onset type 2 diabetes	3.000000e-08
GCST012110_4	Loneliness	1.000000e-08
GCST012114_12	Sociability score	8.000000e-09
GCST90000047_198	Age at first sexual intercourse	2.000000e-08
GCST90002409_44	Childhood body mass index	1.000000e-06

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0009270	heel bone mineral density
EFO:0009592	social interaction measurement
EFO:0007865	loneliness measurement
EFO:0007876	insomnia measurement
EFO:0009749	age at first sexual intercourse measurement
EFO:0004340	body mass index

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295672 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 29,704 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL633	AMIODARONE	4	29,704

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — 1.14.11.- Histone demethylases

ChEMBL bioactivities

1 potent at pChembl≥5 of 2 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.57	IC50	2700	nM	CHEMBL4126235

PubChem BioAssay actives

1 with measured affinity, of 16 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
[(5S)-6-[[(2S)-5-amino-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S,3R)-1-[[2-[[2-[[(2S)-6-amino-1-[[(2S)-1-[(2S)-2-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(1S)-1-carboxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-5-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-aminopropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-hydroxybutanoyl]amino]-6-oxohexyl]-trimethylazanium	1496242: Displacement of C-terminally biotinylated-H3K4me3 (1 to 21 residues) peptide from KDM7C (PHD) (unknown origin) preincubated for 15 mins followed by peptide addition measured after 1 hr by luminescence-based AlphaScreen assay	ic50	2.7000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	6
bisphenol A	increases expression, affects cotreatment	3
sodium arsenite	increases abundance, increases expression	2
Dexamethasone	affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
trichostatin A	affects expression	1
arsenite	affects binding, decreases reaction	1
butyraldehyde	decreases expression	1
coumarin	increases phosphorylation	1
beta-glycerophosphoric acid	affects cotreatment, increases expression	1
1-hydroxypyrene	increases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Air Pollutants, Occupational	increases expression	1
Arsenic	increases abundance, increases expression	1
Ascorbic Acid	affects cotreatment, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Caffeine	decreases phosphorylation	1
Doxorubicin	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Methyl Methanesulfonate	increases expression	1
Smoke	decreases expression	1
Tretinoin	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Antirheumatic Agents	increases expression	1
tert-Butylhydroperoxide	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4122977	Binding	Displacement of C-terminally biotinylated-H3K4me3 (1 to 21 residues) peptide from KDM7C (PHD) (unknown origin) preincubated for 15 mins followed by peptide addition measured after 1 hr by luminescence-based AlphaScreen assay	Investigations on small molecule inhibitors targeting the histone H3K4 tri-methyllysine binding PHD-finger of JmjC histone demethylases. — Bioorg Med Chem

Cellosaurus cell lines

5 cell lines: 3 embryonic stem cell, 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A5H7	SEES3-1V human PHF2, clone1	Embryonic stem cell	Male
CVCL_A5H8	SEES3-1V human PHF2, clone2	Embryonic stem cell	Male
CVCL_A5H9	SEES3-1V human PHF2, clone3	Embryonic stem cell	Male
CVCL_TD11	HAP1 PHF2 (-) 1	Cancer cell line	Male
CVCL_TD12	HAP1 PHF2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer