PHF23

Summary

PHF23 (PHD finger protein 23, HGNC:28428) is a protein-coding gene on chromosome 17p13.1, encoding PHD finger protein 23 (Q9BUL5). Acts as a negative regulator of autophagy, through promoting ubiquitination and degradation of LRSAM1, an E3 ubiquitin ligase that promotes autophagy in response to starvation or infecting bacteria.

Predicted to enable zinc ion binding activity. Involved in negative regulation of autophagosome assembly; negative regulation of autophagosome maturation; and positive regulation of protein ubiquitination. Located in cytosol and nucleoplasm.

Source: NCBI Gene 79142 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 66 total
• Druggable target: yes
• MANE Select transcript: NM_024297

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28428
Approved symbol	PHF23
Name	PHD finger protein 23
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC2941, FLJ16355
Ensembl gene	ENSG00000040633
Ensembl biotype	protein_coding
OMIM	612910
Entrez	79142

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 11 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000320316, ENST00000454255, ENST00000570753, ENST00000570899, ENST00000571362, ENST00000572789, ENST00000573826, ENST00000574236, ENST00000574323, ENST00000574407, ENST00000574899, ENST00000576955, ENST00000613632

RefSeq mRNA: 3 — MANE Select: NM_024297 NM_001284517, NM_001284518, NM_024297

CCDS: CCDS42250, CCDS67143, CCDS67144

Canonical transcript exons

ENST00000320316 — 5 exons

Exon	Start	End
ENSE00001117798	7239246	7239457
ENSE00002631934	7235038	7235840
ENSE00003512596	7235930	7236767
ENSE00003545159	7237629	7237660
ENSE00003625323	7237385	7237477

Expression profiles

Bgee: expression breadth ubiquitous, 247 present calls, max score 93.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.7621 / max 81.4095, expressed in 1790 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
164159	10.1953	1775
164158	1.3384	918
164157	0.2283	77

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	93.82	gold quality
right adrenal gland cortex	UBERON:0035827	93.75	gold quality
right adrenal gland	UBERON:0001233	93.50	gold quality
lower esophagus mucosa	UBERON:0035834	92.99	gold quality
stromal cell of endometrium	CL:0002255	92.96	gold quality
left adrenal gland	UBERON:0001234	92.55	gold quality
left adrenal gland cortex	UBERON:0035825	92.42	gold quality
blood	UBERON:0000178	92.32	gold quality
adrenal cortex	UBERON:0001235	92.01	gold quality
adrenal gland	UBERON:0002369	91.93	gold quality
islet of Langerhans	UBERON:0000006	91.05	gold quality
mucosa of transverse colon	UBERON:0004991	90.97	gold quality
ventricular zone	UBERON:0003053	90.67	gold quality
esophagus mucosa	UBERON:0002469	90.62	gold quality
ganglionic eminence	UBERON:0004023	90.24	gold quality
cortical plate	UBERON:0005343	90.05	gold quality
adrenal tissue	UBERON:0018303	89.98	gold quality
vermiform appendix	UBERON:0001154	89.61	gold quality
esophagus	UBERON:0001043	89.54	gold quality
lymph node	UBERON:0000029	89.50	gold quality
smooth muscle tissue	UBERON:0001135	89.15	gold quality
prefrontal cortex	UBERON:0000451	89.14	gold quality
gall bladder	UBERON:0002110	88.98	gold quality
esophagus squamous epithelium	UBERON:0006920	88.49	gold quality
leukocyte	CL:0000738	88.46	gold quality
spleen	UBERON:0002106	88.43	gold quality
lower esophagus	UBERON:0013473	88.32	gold quality
lower esophagus muscularis layer	UBERON:0035833	88.29	gold quality
metanephros	UBERON:0000081	88.21	gold quality
ileal mucosa	UBERON:0000331	88.19	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.82
E-MTAB-7052	no	66.13
E-HCAD-13	no	3.03

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

52 targeting PHF23, 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-126-5P	100.00	72.71	3180
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
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-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-4699-3P	99.71	70.15	3142

Literature-anchored findings (GeneRIF, showing 3)

• Plant homeodomain finger protein 23 negatively regulates cell autophagy by promoting ubiquitination and degradation of E3 ligase LRSAM1 (PMID:25484098)
• Mechanistic insights into chromatin targeting by leukemic NUP98-PHF23 fusion. (PMID:32620764)
• PHF23 promotes NSCLC proliferation, metastasis, and chemoresistance via stabilization of ACTN4 and activation of the ERK pathway. (PMID:37626047)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	phf23a	ENSDARG00000030887
danio_rerio	phf23b	ENSDARG00000036305
mus_musculus	Phf23	ENSMUSG00000018572
rattus_norvegicus	Phf23	ENSRNOG00000017657

Paralogs (1): PHF13 (ENSG00000116273)

Protein

Protein identifiers

PHD finger protein 23 — Q9BUL5 (reviewed: Q9BUL5)

Alternative names: PDH-containing protein JUNE-1

All UniProt accessions (8): A0A087WVQ2, I3L0X3, I3L0Y2, I3L1N0, I3L2W6, I3L410, I3L4Q4, Q9BUL5

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a negative regulator of autophagy, through promoting ubiquitination and degradation of LRSAM1, an E3 ubiquitin ligase that promotes autophagy in response to starvation or infecting bacteria.

Subunit / interactions. Interacts with LRSAM1.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Widely expressed in human tissues and various cell lines.

Disease relevance. A chromosomal aberration involving PHF23 is found in a patient with acute myeloid leukemia (AML). Translocation t(11;17)(p15;p13) with NUP98.

Domain organisation. The PHD-type zinc-finger domain is required for interaction with LRSAM1 and negative regulation of autophagy.

Similarity. Belongs to the PHF23 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9BUL5-1	1	yes
Q9BUL5-2	2, JUNE1B
Q9BUL5-3	3
Q9BUL5-4	4

RefSeq proteins (3): NP_001271446, NP_001271447, NP_077273* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001965	Znf_PHD	Domain
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR019787	Znf_PHD-finger	Domain

Pfam: PF13831

UniProt features (33 total): modified residue 9, compositionally biased region 8, splice variant 4, region of interest 3, turn 3, strand 2, chain 1, zinc finger region 1, site 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6WXK	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BUL5-F1	61.11	0.16

Functional residue map

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

Catalytic / active sites (1): 120–121 (breakpoint for translocation to form nup98-phf23 oncogene)

Post-translational modifications (9): 1, 124, 147, 150, 165, 315, 316, 317, 400

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 200 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GOBP_REGULATION_OF_AUTOPHAGY, PAX4_01, GOBP_VACUOLE_ORGANIZATION, LFA1_Q6, GCAAGGA_MIR502, AACYNNNNTTCCS_UNKNOWN, AP4_Q6, GOBP_REGULATION_OF_VACUOLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GGGTGGRR_PAX4_03, CAGCTG_AP4_Q5, SP1_Q2_01, GOBP_NEGATIVE_REGULATION_OF_ORGANELLE_ASSEMBLY, GOBP_MACROAUTOPHAGY

GO Biological Process (4): autophagy (GO:0006914), positive regulation of protein ubiquitination (GO:0031398), negative regulation of autophagosome maturation (GO:1901097), negative regulation of autophagosome assembly (GO:1902902)

GO Molecular Function (3): zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
negative regulation of macroautophagy	2
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
protein ubiquitination	1
regulation of protein ubiquitination	1
positive regulation of protein modification by small protein conjugation or removal	1
negative regulation of protein-containing complex disassembly	1
autophagosome maturation	1
regulation of autophagosome maturation	1
autophagosome assembly	1
negative regulation of organelle assembly	1
regulation of autophagosome assembly	1
transition metal ion binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1324 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PHF23	NUP98	P52948	917
PHF23	KDM5A	P29375	859
PHF23	NSD1	Q96L73	725
PHF23	MEIS1	O00470	695
PHF23	DDX10	Q13206	689
PHF23	PSIP1	O75475	676
PHF23	HOXD13	P35453	641
PHF23	NSD3	Q9BZ95	636
PHF23	H3C1	P02295	631
PHF23	H3-5	Q6NXT2	631
PHF23	H3-3A	P06351	628
PHF23	H3-4	Q16695	628
PHF23	H3-7	Q5TEC6	628
PHF23	H3C14	Q71DI3	628
PHF23	HOXA9	P31269	600

IntAct

41 interactions, top by confidence:

A	B	Type	Score
FOXK2	DVL2	psi-mi:“MI:0914”(association)	0.640
CASP6	PHF23	psi-mi:“MI:0915”(physical association)	0.560
PHF23	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
PHF23	GSN	psi-mi:“MI:0915”(physical association)	0.560
PHF23	HRAS	psi-mi:“MI:0915”(physical association)	0.560
LAMP2	PHF23	psi-mi:“MI:0915”(physical association)	0.560
RAN	PHF23	psi-mi:“MI:0915”(physical association)	0.560
KLF11	PHF23	psi-mi:“MI:0915”(physical association)	0.560
PHF23	CYCS	psi-mi:“MI:0915”(physical association)	0.560
HCCS	NPAT	psi-mi:“MI:0914”(association)	0.530
PHF23	ERBB2	psi-mi:“MI:0915”(physical association)	0.370
PHF23	STK11	psi-mi:“MI:0915”(physical association)	0.370
PHF23	SIN3B	psi-mi:“MI:0914”(association)	0.350
HCCS	MPZL1	psi-mi:“MI:0914”(association)	0.350

BioGRID (57): PHF23 (Affinity Capture-MS), LRSAM1 (Affinity Capture-Western), PHF23 (Affinity Capture-Western), LRSAM1 (Reconstituted Complex), PHF23 (Two-hybrid), PHF23 (Two-hybrid), PHF23 (Affinity Capture-MS), PHF23 (Affinity Capture-MS), SIN3A (Affinity Capture-MS), SAP130 (Affinity Capture-MS), ARID4B (Affinity Capture-MS), SIN3B (Affinity Capture-MS), SAP30 (Affinity Capture-MS), SUDS3 (Affinity Capture-MS), BRMS1L (Affinity Capture-MS)

ESM2 similar proteins: A0A8I5ZM56, A2AG50, A2AI08, A2AJI0, A5D7K1, D4A4L4, E1C2Q8, F1LR10, O00515, O14529, O75128, O88573, O88735, P51825, P57016, Q14244, Q32LQ1, Q3KQU3, Q3U2K0, Q5JTD0, Q5PR69, Q5R7F9, Q5XHX2, Q5ZIA2, Q5ZJJ1, Q68DK7, Q6IPM2, Q6NV74, Q6NZF1, Q6P9J5, Q6PDH0, Q6PDM1, Q6PG95, Q6ZU35, Q86UU1, Q8CCJ4, Q8K124, Q8N7J2, Q8TD55, Q96PV7

Diamond homologs: A5D962, Q0IHB0, Q5BJ10, Q5HZN9, Q5U5E5, Q6AY75, Q7SXB5, Q86YI8, Q8BSN5, Q8K2W6, Q9BUL5, Q08D35, O75151, Q8BLG0, Q9BVI0, Q9FEN9, Q9WTU0, O44498, Q9U263

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	56
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

960 predictions. Top by Δscore:

Variant	Effect	Δscore
17:7235929:C:CG	donor_loss	1.0000
17:7236763:CTTTC:C	acceptor_gain	1.0000
17:7236767:CCT:C	acceptor_gain	1.0000
17:7236769:T:C	acceptor_gain	1.0000
17:7236769:T:TC	acceptor_gain	1.0000
17:7237384:CCT:C	donor_gain	1.0000
17:7237427:A:C	donor_gain	1.0000
17:7237478:C:CC	acceptor_gain	1.0000
17:7237625:TCAC:T	donor_loss	1.0000
17:7237626:CAC:C	donor_loss	1.0000
17:7237627:AC:A	donor_loss	1.0000
17:7237661:C:CC	acceptor_gain	1.0000
17:7236655:A:C	donor_gain	0.9900
17:7236768:C:CC	acceptor_gain	0.9900
17:7236768:C:T	acceptor_gain	0.9900
17:7237379:CCCTA:C	donor_loss	0.9900
17:7237380:CCTA:C	donor_loss	0.9900
17:7237381:CTAC:C	donor_loss	0.9900
17:7237382:TA:T	donor_loss	0.9900
17:7237383:A:C	donor_loss	0.9900
17:7237384:CC:C	donor_loss	0.9900
17:7237474:GTGG:G	acceptor_gain	0.9900
17:7237475:TGG:T	acceptor_gain	0.9900
17:7237475:TGGC:T	acceptor_loss	0.9900
17:7237476:GG:G	acceptor_gain	0.9900
17:7237477:GC:G	acceptor_loss	0.9900
17:7237479:T:C	acceptor_loss	0.9900
17:7237659:ATCTG:A	acceptor_loss	0.9900
17:7237660:TCT:T	acceptor_loss	0.9900
17:7237661:C:A	acceptor_loss	0.9900

AlphaMissense

2610 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:7235686:G:C	C384W	1.000
17:7235687:C:G	C384S	1.000
17:7235687:C:T	C384Y	1.000
17:7235688:A:G	C384R	1.000
17:7235688:A:T	C384S	1.000
17:7235695:G:C	C381W	1.000
17:7235696:C:A	C381F	1.000
17:7235696:C:G	C381S	1.000
17:7235696:C:T	C381Y	1.000
17:7235697:A:G	C381R	1.000
17:7235697:A:T	C381S	1.000
17:7235701:A:C	F379L	1.000
17:7235701:A:T	F379L	1.000
17:7235702:A:C	F379C	1.000
17:7235702:A:G	F379S	1.000
17:7235703:A:G	F379L	1.000
17:7235711:G:T	P376H	1.000
17:7235712:G:A	P376S	1.000
17:7235714:A:T	V375D	1.000
17:7235725:C:A	K371N	1.000
17:7235725:C:G	K371N	1.000
17:7235729:A:C	I370S	1.000
17:7235729:A:G	I370T	1.000
17:7235729:A:T	I370N	1.000
17:7235735:G:T	A368D	1.000
17:7235737:A:C	C367W	1.000
17:7235738:C:A	C367F	1.000
17:7235738:C:G	C367S	1.000
17:7235738:C:T	C367Y	1.000
17:7235739:A:C	C367G	1.000

dbSNP variants (sampled 300 via entrez): RS1000459012 (17:7240108 A>C,G), RS1000557803 (17:7240386 G>A), RS1000598225 (17:7235015 G>A,C), RS1000676156 (17:7234567 C>T), RS1002182880 (17:7241521 C>T), RS1002226595 (17:7236423 G>A,T), RS1002232858 (17:7237790 G>A,C), RS1002279024 (17:7236842 A>C), RS1003310370 (17:7242394 C>G), RS1004287789 (17:7239848 C>G), RS1004320392 (17:7240735 A>G), RS1004599170 (17:7234744 C>T), RS1004782423 (17:7234627 T>A,C,G), RS1006317345 (17:7237828 C>A,G,T), RS1006399553 (17:7235557 C>A)

Disease associations

OMIM: gene MIM:612910 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST90002388_485	Lymphocyte count	2.000000e-17
GCST90002389_221	Lymphocyte percentage of white cells	5.000000e-19
GCST90002399_280	Neutrophil percentage of white cells	9.000000e-12

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2424508 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	4
trichostatin A	affects expression, decreases expression	2
Formaldehyde	decreases expression	2
Lead	affects expression, affects methylation	2
Cyclosporine	decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression	1
sodium arsenite	increases expression	1
ferrous chloride	decreases expression	1
coumarin	affects phosphorylation	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
Leflunomide	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants, Occupational	decreases expression	1
Arsenic	affects methylation	1
Atrazine	decreases expression	1
Caffeine	decreases phosphorylation	1
Ethyl Methanesulfonate	decreases expression	1
Ivermectin	decreases expression	1
Methotrexate	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Nickel	decreases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2429071	Binding	Inhibition of PHF23 (unknown origin) after 30 mins by AlphaScreen assay	Small-molecule ligands of methyl-lysine binding proteins: optimization of selectivity for L3MBTL3. — J Med Chem

Cellosaurus cell lines

2 cell lines: 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3DS	Abcam HEK293T PHF23 KO	Transformed cell line	Female
CVCL_E1FS	Abcam HEK293 PHF23 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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