PHF13

Summary

PHF13 (PHD finger protein 13, HGNC:22983) is a protein-coding gene on chromosome 1p36.31, encoding PHD finger protein 13 (Q86YI8). Modulates chromatin structure and DNA damage response by regulating key determinants of chromatin compaction and DNA damage response.

Enables chromatin binding activity; chromatin-protein adaptor activity; and methylated histone binding activity. Involved in mitotic chromosome condensation and regulation of DNA repair. Located in nucleus.

Source: NCBI Gene 148479 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 49 total
• Druggable target: yes
• MANE Select transcript: NM_153812

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22983
Approved symbol	PHF13
Name	PHD finger protein 13
Location	1p36.31
Locus type	gene with protein product
Status	Approved
Aliases	MGC43399
Ensembl gene	ENSG00000116273
Ensembl biotype	protein_coding
OMIM	620054
Entrez	148479

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000377648, ENST00000495385, ENST00000961800

RefSeq mRNA: 1 — MANE Select: NM_153812 NM_153812

CCDS: CCDS85

Canonical transcript exons

ENST00000377648 — 4 exons

Exon	Start	End
ENSE00000736135	6619803	6620337
ENSE00001248376	6616757	6616858
ENSE00001474710	6621411	6624030
ENSE00001474722	6613731	6614105

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 98.07.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.0723 / max 148.6047, expressed in 1794 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
408	11.0696	1768
409	3.4612	1402
410	2.4616	1169
411	0.0799	25

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.07	gold quality
oocyte	CL:0000023	97.92	gold quality
cartilage tissue	UBERON:0002418	94.82	gold quality
adult organism	UBERON:0007023	94.23	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.71	gold quality
upper arm skin	UBERON:0004263	92.80	gold quality
vena cava	UBERON:0004087	92.16	gold quality
tibialis anterior	UBERON:0001385	91.88	gold quality
nipple	UBERON:0002030	91.09	gold quality
epithelium of mammary gland	UBERON:0003244	90.86	gold quality
mammary duct	UBERON:0001765	90.82	gold quality
testis	UBERON:0000473	90.71	gold quality
right testis	UBERON:0004534	90.64	gold quality
saphenous vein	UBERON:0007318	90.48	gold quality
left testis	UBERON:0004533	90.44	gold quality
pancreatic ductal cell	CL:0002079	90.25	gold quality
cauda epididymis	UBERON:0004360	89.52	gold quality
upper leg skin	UBERON:0004262	89.34	gold quality
endothelial cell	CL:0000115	89.11	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.06	gold quality
stromal cell of endometrium	CL:0002255	87.93	gold quality
ileal mucosa	UBERON:0000331	87.91	gold quality
caput epididymis	UBERON:0004358	87.66	gold quality
cardiac muscle of right atrium	UBERON:0003379	87.65	silver quality
oviduct epithelium	UBERON:0004804	87.62	gold quality
tibia	UBERON:0000979	87.54	gold quality
corpus epididymis	UBERON:0004359	87.49	gold quality
ventricular zone	UBERON:0003053	87.44	gold quality
esophagus squamous epithelium	UBERON:0006920	87.25	gold quality
seminal vesicle	UBERON:0000998	87.14	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.58

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

122 targeting PHF13, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753

Literature-anchored findings (GeneRIF, showing 6)

• SPOC1 modulates chromatin structure and that tight regulation of its expression levels and subcellular localization during mitosis are crucial for proper chromosome condensation and cell division. (PMID:19638409)
• SPOC1-mediated restriction imposed upon Ad growth is relieved by its functional association with the Ad major core protein pVII that enters with the viral genome, followed by E1B-55K/E4orf6-dependent proteasomal degradation of SPOC1. (PMID:24278021)
• These experiments showed that PHF13 binds specifically to DNA and to two types of histone H3 methyl tags (lysine 4-tri-methyl or lysine 4-di-methyl) where it functions as a transcriptional co-regulator. (PMID:27223324)
• PHF13 has opposing effects throughout the HIV-1 replication cycle (figure 8). After viral entry and nuclear import of the PIC, PHF13 can increase the number of integrated HIV-1 proviral genomes. After integration, PHF13 acts as antiviral restriction factor and inhibits viral gene expression. (PMID:29021215)
• High SPOC1 expression is associated with Cytomegalovirus infections. (PMID:29743358)
• PHF13 epigenetically activates TGFbeta driven epithelial to mesenchymal transition. (PMID:35597793)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	phf13	ENSDARG00000102023
mus_musculus	Phf13	ENSMUSG00000047777
rattus_norvegicus	Phf13	ENSRNOG00000009046

Paralogs (1): PHF23 (ENSG00000040633)

Protein

Protein identifiers

PHD finger protein 13 — Q86YI8 (reviewed: Q86YI8)

Alternative names: Survival time-associated PHD finger protein in ovarian cancer 1

All UniProt accessions (2): A0A158RFV6, Q86YI8

UniProt curated annotations — full annotation on UniProt →

Function. Modulates chromatin structure and DNA damage response by regulating key determinants of chromatin compaction and DNA damage response. Binds H3K4me3-containing chromatin and promotes DNA condensation by recruiting corepressors such as TRIM28 and H3K9 methyltransferase SETDB1. Required for normal chromosome condensation during the early stages of mitosis. Required for normal chromosome separation during mitosis. Increases both chromatin-associated levels and activity of H3K9 methyltransferases, such as SETDB1, thus enhancing H3K9 trimethylation. Essential for testicular stem-cell differentiation and sustained spermatogenesis.

Subunit / interactions. Interacts with histone H3 that is trimethylated at ‘Lys-4’ (H3K4me3) (PubMed:23034801, Ref.10). Interacts with GSK3B. Interacts with TRIM28. Interacts with SETDB1; the interaction probably enhances SETDB1 chromatin-associated levels and activity.

Subcellular location. Nucleus. Nucleoplasm.

Post-translational modifications. Subject to proteasomal degradation. Stable when bound to chromatin. The soluble form is rapidly degraded.

Induction. Expression levels are tightly regulated during the cell cycle. Strongly up-regulated during late G2 phase and M phase of the mitotic cell cycle. Down-regulated at the G1-S phase transition of the cell cycle.

RefSeq proteins (1): NP_722519* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001965	Znf_PHD	Domain
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR041947	PHD_PHF13	Domain

Pfam: PF20826

UniProt features (16 total): compositionally biased region 3, strand 2, turn 2, helix 2, region of interest 2, chain 1, zinc finger region 1, short sequence motif 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3O7A	X-RAY DIFFRACTION	1.67
3O70	X-RAY DIFFRACTION	1.85

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86YI8-F1	64.80	0.22

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 208 (showing top): E2F_Q4, GOBP_CHROMOSOME_ORGANIZATION, MAZ_Q6, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, WHITE_NEUROBLASTOMA_WITH_1P36.3_DELETION, GGAMTNNNNNTCCY_UNKNOWN, GOBP_CHROMOSOME_CONDENSATION, E2F_Q3, GOBP_ORGANELLE_FISSION, GOBP_MITOTIC_NUCLEAR_DIVISION, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, GOBP_DNA_DAMAGE_RESPONSE, AAAGGGA_MIR204_MIR211, GOBP_MITOTIC_CELL_CYCLE, AACTTT_UNKNOWN

GO Biological Process (7): mitotic cell cycle (GO:0000278), DNA damage response (GO:0006974), chromosome segregation (GO:0007059), mitotic chromosome condensation (GO:0007076), cell division (GO:0051301), chromatin organization (GO:0006325), chromosome condensation (GO:0030261)

GO Molecular Function (6): chromatin binding (GO:0003682), zinc ion binding (GO:0008270), histone H3K9me2/3 reader activity (GO:0062072), chromatin-protein adaptor activity (GO:0140463), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (2): nucleus (GO:0005634), nucleoplasm (GO:0005654)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
cell cycle	1
mitotic nuclear division	1
cellular response to stress	1
cell cycle process	1
mitotic sister chromatid segregation	1
mitotic cell cycle	1
chromosome condensation	1
mitotic cell cycle process	1
cellular process	1
cellular component organization	1
chromosome organization	1
transition metal ion binding	1
histone H3 reader activity	1
chromatin binding	1
chromatin organization	1
protein-macromolecule adaptor activity	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1344 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PHF13	PHF1	O43189	676
PHF13	ATM	Q13315	542
PHF13	TRIM28	Q13263	509
PHF13	CDK5	Q00535	499
PHF13	ZGPAT	Q8N5A5	446
PHF13	MAPT	P10636	445
PHF13	SMUG1	Q53HV7	437
PHF13	HLTF	Q14527	410
PHF13	EME1	Q96AY2	405
PHF13	GSK3A	P49840	401
PHF13	PHF5A	Q7RTV0	400
PHF13	CBX7	O95931	394
PHF13	PKIG	Q9Y2B9	393
PHF13	TPO	P07202	391
PHF13	MCM10	Q7L590	391

IntAct

6 interactions, top by confidence:

A	B	Type	Score
PHF13	DNASE1L2	psi-mi:“MI:0914”(association)	0.530
PHF13	SIN3A	psi-mi:“MI:0915”(physical association)	0.400
PHF13	CPTP	psi-mi:“MI:0915”(physical association)	0.370
PHF21B	KDM1A	psi-mi:“MI:0914”(association)	0.350
PHF13	BLVRA	psi-mi:“MI:0914”(association)	0.350

BioGRID (22): TBX20 (Affinity Capture-MS), DNASE1L2 (Affinity Capture-MS), PPIE (Affinity Capture-MS), TBX20 (Affinity Capture-MS), DNASE1L2 (Affinity Capture-MS), PPIE (Affinity Capture-MS), PHF13 (Affinity Capture-MS), PHF13 (Affinity Capture-MS), PHF13 (Affinity Capture-MS), PHF13 (Affinity Capture-MS), PHF13 (Affinity Capture-MS), PPIE (Affinity Capture-MS), TBX20 (Affinity Capture-MS), BLVRA (Affinity Capture-MS), DNASE1L2 (Affinity Capture-MS)

ESM2 similar proteins: A0A088MLT8, A2AQ25, B3KU38, B5DF41, E9PSK7, O15079, O35274, P0DPB3, P0DPB4, P12755, P49140, P85299, Q0D2I5, Q14DQ1, Q1LY51, Q3B7M3, Q3SYW5, Q4KMA0, Q4R3X1, Q50H33, Q5F3L9, Q5FVG6, Q5RD40, Q5XKK7, Q60698, Q6ZNC4, Q6ZUS6, Q6ZWB6, Q80U23, Q80U62, Q80XA6, Q812A5, Q86YI8, Q8BXL9, Q8K2W6, Q8ND83, Q8NFH8, Q8QFX1, Q8TEK3, Q924W7

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

633 predictions. Top by Δscore:

Variant	Effect	Δscore
1:6616752:A:AG	acceptor_gain	1.0000
1:6616752:AATAG:A	acceptor_gain	1.0000
1:6616753:A:G	acceptor_gain	1.0000
1:6616753:ATAG:A	acceptor_gain	1.0000
1:6616754:TA:T	acceptor_loss	1.0000
1:6616755:A:AG	acceptor_gain	1.0000
1:6616755:A:G	acceptor_loss	1.0000
1:6616755:AG:A	acceptor_gain	1.0000
1:6616756:G:GG	acceptor_gain	1.0000
1:6616756:GG:G	acceptor_gain	1.0000
1:6616756:GGA:G	acceptor_gain	1.0000
1:6616756:GGAA:G	acceptor_gain	1.0000
1:6616756:GGAAT:G	acceptor_gain	1.0000
1:6616855:GGAG:G	donor_gain	1.0000
1:6616856:G:GT	donor_gain	1.0000
1:6616856:G:T	donor_gain	1.0000
1:6616856:GAGGT:G	donor_loss	1.0000
1:6616857:AGGTA:A	donor_loss	1.0000
1:6616859:G:GC	donor_loss	1.0000
1:6616860:T:G	donor_loss	1.0000
1:6620338:G:GG	donor_gain	1.0000
1:6620338:GTGA:G	donor_loss	1.0000
1:6614102:GGAG:G	donor_gain	0.9900
1:6614103:GAG:G	donor_gain	0.9900
1:6614103:GAGG:G	donor_gain	0.9900
1:6614104:AGG:A	donor_loss	0.9900
1:6614106:G:A	donor_loss	0.9900
1:6614107:T:G	donor_loss	0.9900
1:6619798:TTTA:T	acceptor_loss	0.9900
1:6619800:TAGGA:T	acceptor_gain	0.9900

AlphaMissense

1986 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:6616799:T:C	F28L	1.000
1:6616800:T:C	F28S	1.000
1:6616800:T:G	F28C	1.000
1:6616801:C:A	F28L	1.000
1:6616801:C:G	F28L	1.000
1:6616808:T:C	F31L	1.000
1:6616809:T:C	F31S	1.000
1:6616809:T:G	F31C	1.000
1:6616810:C:A	F31L	1.000
1:6616810:C:G	F31L	1.000
1:6616811:T:C	C32R	1.000
1:6616812:G:A	C32Y	1.000
1:6616812:G:T	C32F	1.000
1:6616813:C:G	C32W	1.000
1:6616821:T:A	V35D	1.000
1:6616824:T:C	L36S	1.000
1:6616824:T:G	L36W	1.000
1:6616829:T:G	Y38D	1.000
1:6616833:C:A	A39D	1.000
1:6620323:T:A	I221N	1.000
1:6620323:T:G	I221S	1.000
1:6620326:T:A	M222K	1.000
1:6620326:T:G	M222R	1.000
1:6621422:T:A	W230R	1.000
1:6621422:T:C	W230R	1.000
1:6621424:G:C	W230C	1.000
1:6621424:G:T	W230C	1.000
1:6621429:T:C	L232P	1.000
1:6621437:T:A	C235S	1.000
1:6621437:T:C	C235R	1.000

dbSNP variants (sampled 300 via entrez): RS1000349690 (1:6611734 TG>T), RS1000489825 (1:6615094 G>C), RS1000626728 (1:6618609 T>C), RS1000696729 (1:6619911 C>T), RS1000747780 (1:6614675 C>A,T), RS1000826627 (1:6614589 G>A,T), RS1001039185 (1:6624080 A>C,G), RS1001056666 (1:6621229 GGGTAATACCT>G), RS1001152848 (1:6618867 G>A), RS1001352105 (1:6615619 T>G), RS1001361630 (1:6614711 A>C,T), RS1001489005 (1:6620262 G>A,T), RS1001699488 (1:6615390 C>A,T), RS1001824357 (1:6621720 C>A,T), RS1001979143 (1:6616169 C>T)

Disease associations

OMIM: gene MIM:620054 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST006979_849	Heel bone mineral density	6.000000e-24
GCST007430_71	Peak expiratory flow	2.000000e-09
GCST007431_105	Lung function (FEV1/FVC)	6.000000e-23
GCST007432_26	FEV1	7.000000e-06
GCST007930_138	Medication use (agents acting on the renin-angiotensin system)	5.000000e-11
GCST007931_51	Medication use (HMG CoA reductase inhibitors)	2.000000e-09

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0009718	peak expiratory flow
EFO:0004713	FEV/FVC ratio
EFO:0004314	forced expiratory volume
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0009932	HMG CoA reductase inhibitor use measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1764945 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	2
sodium arsenite	decreases expression, increases abundance, increases expression	2
Benzo(a)pyrene	affects methylation, increases expression	2
Formaldehyde	increases expression, decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	decreases phosphorylation	1
TAK-243	increases sumoylation	1
cupric chloride	increases expression	1
beta-methylcholine	affects 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
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	decreases expression, increases abundance	1
Atrazine	increases expression	1
Benzene	increases expression	1
Caffeine	increases phosphorylation	1
Cisplatin	increases expression	1
Methyl Methanesulfonate	increases expression	1
Phenobarbital	affects expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Cyclosporine	increases expression	1
Antirheumatic Agents	increases expression	1
Copper Sulfate	increases expression	1
Acrylamide	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1767463	Binding	Binding affinity to PHF13 by chemiluminescent assay	Small-molecule ligands of methyl-lysine binding proteins. — J Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TD09	HAP1 PHF13 (-) 1	Cancer cell line	Male
CVCL_TD10	HAP1 PHF13 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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