PHF19

Summary

PHF19 (PHD finger protein 19, HGNC:24566) is a protein-coding gene on chromosome 9q33.2, encoding PHD finger protein 19 (Q5T6S3). Polycomb group (PcG) protein that specifically binds histone H3 trimethylated at ‘Lys-36’ (H3K36me3) and recruits the PRC2 complex, thus enhancing PRC2 H3K27me3 methylation activity.

Enables methylated histone binding activity. Involved in negative regulation of gene expression, epigenetic. Located in ESC/E(Z) complex.

Source: NCBI Gene 26147 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 63 total
• Druggable target: yes
• MANE Select transcript: NM_015651

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24566
Approved symbol	PHF19
Name	PHD finger protein 19
Location	9q33.2
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP727G051, PCL3, MTF2L1, TDRD19B
Ensembl gene	ENSG00000119403
Ensembl biotype	protein_coding
OMIM	609740
Entrez	26147

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 11 protein_coding, 3 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000312189, ENST00000373896, ENST00000419155, ENST00000436309, ENST00000439674, ENST00000453868, ENST00000456291, ENST00000462229, ENST00000464712, ENST00000467266, ENST00000474402, ENST00000478371, ENST00000487555, ENST00000616568, ENST00000866651, ENST00000866652, ENST00000866653

RefSeq mRNA: 5 — MANE Select: NM_015651 NM_001009936, NM_001286840, NM_001286842, NM_001286843, NM_015651

CCDS: CCDS35116, CCDS35117, CCDS69648, CCDS75889

Canonical transcript exons

ENST00000373896 — 15 exons

Exon	Start	End
ENSE00001198618	120869182	120869330
ENSE00001198622	120869845	120869945
ENSE00001369777	120874556	120874756
ENSE00001370238	120873979	120874060
ENSE00001378247	120870443	120870538
ENSE00001461866	120855651	120858286
ENSE00001883499	120877091	120877188
ENSE00003496939	120864049	120864116
ENSE00003523321	120865710	120865830
ENSE00003541654	120862588	120862749
ENSE00003555944	120861918	120862005
ENSE00003579815	120866870	120866965
ENSE00003618314	120861089	120861174
ENSE00003644291	120866028	120866096
ENSE00003651655	120860090	120860185

Expression profiles

Bgee: expression breadth ubiquitous, 240 present calls, max score 96.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.3360 / max 277.1923, expressed in 1678 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
102308	12.0725	1507
102310	3.0454	1112
102309	2.2780	950
102307	0.8356	409
102306	0.7626	336
102305	0.3419	137

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	96.43	gold quality
descending thoracic aorta	UBERON:0002345	94.85	gold quality
thoracic aorta	UBERON:0001515	93.98	gold quality
mucosa of stomach	UBERON:0001199	93.92	gold quality
ascending aorta	UBERON:0001496	93.92	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.66	gold quality
granulocyte	CL:0000094	93.44	gold quality
adenohypophysis	UBERON:0002196	93.31	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.05	gold quality
lower esophagus	UBERON:0013473	93.03	gold quality
aorta	UBERON:0000947	93.02	gold quality
ganglionic eminence	UBERON:0004023	92.57	gold quality
embryo	UBERON:0000922	92.56	gold quality
lymph node	UBERON:0000029	92.46	gold quality
popliteal artery	UBERON:0002250	92.42	gold quality
tibial artery	UBERON:0007610	92.41	gold quality
right coronary artery	UBERON:0001625	92.32	gold quality
right ovary	UBERON:0002118	92.24	gold quality
left ovary	UBERON:0002119	92.18	gold quality
left uterine tube	UBERON:0001303	92.09	gold quality
left coronary artery	UBERON:0001626	91.66	gold quality
smooth muscle tissue	UBERON:0001135	91.58	gold quality
endocervix	UBERON:0000458	91.34	gold quality
tibial nerve	UBERON:0001323	91.30	gold quality
coronary artery	UBERON:0001621	91.21	gold quality
pituitary gland	UBERON:0000007	91.10	gold quality
vermiform appendix	UBERON:0001154	91.10	gold quality
lower esophagus mucosa	UBERON:0035834	90.89	gold quality
ectocervix	UBERON:0012249	90.87	gold quality
body of uterus	UBERON:0009853	90.81	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-9467	yes	33.70
E-HCAD-13	yes	22.91
E-CURD-122	yes	22.59
E-HCAD-1	yes	18.07
E-ANND-3	yes	4.15
E-CURD-84	no	445.36

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

102 targeting PHF19, 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-4692	100.00	67.32	2066
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-219A-5P	99.91	73.36	735
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4782-3P	99.88	73.31	735
HSA-MIR-6766-3P	99.88	73.38	732

Literature-anchored findings (GeneRIF, showing 21)

• identification of a gene encoding a human homologue of the Drosophila polycomblike protein, hPCL3 gene, encoding two nuclear proteins, hPCL3S and hPCL3L; markedly overexpressed in many types of cancers (PMID:15563832)
• Functional characterization of human Polycomb-like 3 isoforms identifies them as components of distinct EZH2 protein complexes (PMID:21143197)
• PHF19 silencing reduces the cell proliferation rate and increases the transendothelial migration capacities of melanoma cell lines. (PMID:22487681)
• propose a model whereby PHF19 functions during mouse embryonic stem cell differentiation to transiently bind the H3K36me3 mark via its Tudor domain (PMID:23160351)
• The histone H3K36me3 binding by the Tudor domains of PHF1, PHF19 and likely MTF2 provide another recruitment and regulatory mechanism for the PRC2 complex (PMID:23228662)
• These results provide evidence that PHF19 promotes Hepatocellular carcinoma and is regulated by the tumor-suppressor, miR-195-5p (PMID:25955388)
• G9a promotes H3K27 methylation of the E-cadherin promoter by upregulating PCL3 to increase PRC2 promoter recruitment and by downregulating the H3K27 demethylase KDM7A to silence E-cadherin gene (PMID:26688070)
• human PCL3 has an oncogenic role in hepatocellular carcinoma by activating the beta-catenin/IL6 signaling axis to promote metastasis. (PMID:29483096)
• miR-124a suppresses PHF19 over-expression, EZH2 hyper-activation, and aberrant glioma cell proliferation (PMID:30131250)
• PHF19 promotes the proliferation, migration, and chemosensitivity of glioblastoma to doxorubicin through modulation of the SIAH1/beta-catenin axis. (PMID:30323224)
• PHF19 is positively correlated with poorer clinic outcomes of multiple myeloma and essential for multiple myeloma growth in vitro and in vivo. PHF19 potentiates tumorigenicity via PRC2 activation and H3K27me3 spreading. (PMID:31383640)
• Multiple Myeloma DREAM Challenge reveals epigenetic regulator PHF19 as marker of aggressive disease. (PMID:32060406)
• PHF19 mediated regulation of proliferation and invasiveness in prostate cancer cells. (PMID:32155117)
• Polycomb-like Protein 3 Induces Proliferation and Drug Resistance in Multiple Myeloma and Is Regulated by miRNA-15a. (PMID:32312841)
• Downregulation of PHF19 inhibits cell growth and migration in gastric cancer. (PMID:32449434)
• PHF19 inhibition as a therapeutic target in multiple myeloma. (PMID:33894670)
• LINC_00355 promotes gastric cancer progression by upregulating PHF19 expression through sponging miR-15a-5p. (PMID:34078310)
• PHF19 activates hedgehog signaling and promotes tumorigenesis in hepatocellular carcinoma. (PMID:34129846)
• PHD finger protein 19 expression in multiple myeloma: Association with clinical features, induction therapy outcome, disease progression, and survival. (PMID:34390275)
• Regulation of hPCL3 isoforms’ ubiquitination by TRIM21 in non-small cell lung cancer progression. (PMID:37507137)
• 1q amplification and PHF19 expressing high-risk cells are associated with relapsed/refractory multiple myeloma. (PMID:38755140)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	phf19	ENSDARG00000078050
mus_musculus	Phf19	ENSMUSG00000026873
rattus_norvegicus	Phf19	ENSRNOG00000018874
drosophila_melanogaster	Pcl	FBGN0003044

Paralogs (2): PHF1 (ENSG00000112511), MTF2 (ENSG00000143033)

Protein

Protein identifiers

PHD finger protein 19 — Q5T6S3 (reviewed: Q5T6S3)

Alternative names: Polycomb-like protein 3

All UniProt accessions (7): Q5T6S3, A0A087X169, B0QZ50, B0QZ51, B0QZ72, F5H8K3, X6RER8

UniProt curated annotations — full annotation on UniProt →

Function. Polycomb group (PcG) protein that specifically binds histone H3 trimethylated at ‘Lys-36’ (H3K36me3) and recruits the PRC2 complex, thus enhancing PRC2 H3K27me3 methylation activity. Probably involved in the transition from an active state to a repressed state in embryonic stem cells: acts by binding to H3K36me3, a mark for transcriptional activation, and recruiting H3K36me3 histone demethylases RIOX1 or KDM2B, leading to demethylation of H3K36 and recruitment of the PRC2 complex that mediates H3K27me3 methylation, followed by de novo silencing. Recruits the PRC2 complex to CpG islands and contributes to embryonic stem cell self-renewal. Also binds histone H3 dimethylated at ‘Lys-36’ (H3K36me2). Isoform 1 and isoform 2 inhibit transcription from an HSV-tk promoter.

Subunit / interactions. Associates with the PRC2 complex, which consists of the core components EED, EZH1 or EZH2, SUZ12, and RBBP4, and various combinations of accessory subunits including AEBP2, JARID2, PHF19, MTF2 and EPOP. Forms a dimeric PRC2.1 (class 1, PRC-PCL) complex consisting of at least SUZ12, RBBP4, and PHF19 or MTF2; PHF19 and MTF2 stabilize the dimeric structure which enhances PRC2 interaction with chromatin. Interacts with SUZ12; competes with AEBP2 for SUZ12 binding. Interacts with EZH2 (via its Tudor domain). Isoform 1 interacts with SUZ12; isoform 2 does not interact with SUZ12. Interacts with RIOX1.

Subcellular location. Nucleus.

Tissue specificity. Isoform 1 is expressed in thymus, heart, lung and kidney. Isoform 2 is predominantly expressed in placenta, skeletal muscle and kidney, whereas isoform 1 is predominantly expressed in liver and peripheral blood leukocytes. Overexpressed in many types of cancers, including colon, skin, lung, rectal, cervical, uterus, liver cancers, in cell lines derived from different stages of melanoma and in glioma cell lines.

Domain organisation. The Tudor domain recognizes and binds H3K36me3. May also bind H3K27me3, with a lower affinity.

Miscellaneous. Down-regulated in spheroid melanoma cells that display an invasive phenotype, characterized by a higher motility, a poor proliferation rate and a gain of pluripotency gene expression. PHF19 favors the proliferation and reduces the transmigration capacity of melanoma cell lines, 2 properties of invasive cells, suggesting that down-regulation may participate in the switch from proliferative to invasive states in melanoma cells.

Similarity. Belongs to the Polycomblike family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q5T6S3-1	1, PCL3L, hPCL3L	yes
Q5T6S3-2	2, PCL3S, hPCL3S
Q5T6S3-3	3

RefSeq proteins (5): NP_001009936, NP_001273769, NP_001273771, NP_001273772, NP_056466* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001965	Znf_PHD	Domain
IPR002999	Tudor	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
IPR025894	Mtf2_C_dom	Domain
IPR040477	KDM4-like_Tudor	Domain
IPR042017	PHF19_PHD2	Domain
IPR047400	Tudor_PHF19	Domain

Pfam: PF00628, PF14061, PF18104

UniProt features (39 total): strand 7, modified residue 5, region of interest 5, splice variant 4, mutagenesis site 4, helix 3, compositionally biased region 2, site 2, zinc finger region 2, turn 2, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
6WAU	X-RAY DIFFRACTION	1.75
9XZI	X-RAY DIFFRACTION	2.69
6NQ3	X-RAY DIFFRACTION	2.89
2E5Q	SOLUTION NMR
4BD3	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5T6S3-F1	69.87	0.45

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 (2): 47 (histone h3k36me3 binding); 55 (histone h3k36me3 binding)

Post-translational modifications (5): 13, 187, 365, 366, 166

Mutagenesis-validated functional residues (4):

Position	Phenotype
50	in muthphf19; abolishes histone h3k36me3-binding and impaired activity of the prc2 complex and subsequent h3k27me3 methy
50	abolishes histone h3k36me3-binding and recruitment of the prc2 complex and riox1; when associated with a-56.
56	abolishes histone h3k36me3-binding. abolishes histone h3k36me3-binding and recruitment of the prc2 complex and riox1; wh
331–332	impairs chromatin binding as part of the prc2 complex.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212300	PRC2 methylates histones and DNA

MSigDB gene sets: 196 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GSE45365_NK_CELL_VS_CD11B_DC_UP, GCACCTT_MIR18A_MIR18B, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GTGCCTT_MIR506, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, CATTTCA_MIR203, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, GOBP_MAINTENANCE_OF_CELL_NUMBER, LIAO_METASTASIS, FUJII_YBX1_TARGETS_DN, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_UP, FISCHER_DREAM_TARGETS, BASAKI_YBX1_TARGETS_UP

GO Biological Process (6): negative regulation of transcription by RNA polymerase II (GO:0000122), stem cell population maintenance (GO:0019827), negative regulation of gene expression, epigenetic (GO:0045814), stem cell differentiation (GO:0048863), chromatin organization (GO:0006325), epigenetic regulation of gene expression (GO:0040029)

GO Molecular Function (7): DNA binding (GO:0003677), chromatin binding (GO:0003682), zinc ion binding (GO:0008270), histone H3K4me3 reader activity (GO:0140002), histone H3K36me3 reader activity (GO:0140003), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), ESC/E(Z) complex (GO:0035098)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Epigenetic regulation of gene expression	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
histone H3 reader activity	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
multicellular organismal process	1
maintenance of cell number	1
negative regulation of gene expression	1
epigenetic regulation of gene expression	1
cell differentiation	1
cellular component organization	1
chromatin remodeling	1
regulation of gene expression	1
nucleic acid binding	1
transition metal ion binding	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
PcG protein complex	1
histone methyltransferase complex	1

Protein interactions and networks

STRING

1218 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PHF19	EPOP	A6NHQ4	988
PHF19	MTF2	Q9Y483	941
PHF19	RIOX1	Q9H6W3	941
PHF19	PHF1	O43189	899
PHF19	JARID2	Q92833	895
PHF19	AEBP2	Q6ZN18	870
PHF19	EZH2	Q15910	820
PHF19	SUZ12	Q15022	767
PHF19	LCOR	Q96JN0	766
PHF19	EZH1	Q92800	758
PHF19	H3C1	P02295	736
PHF19	RBBP4	P31149	736
PHF19	RBBP7	Q16576	724
PHF19	KDM2B	Q8NHM5	711
PHF19	H3-4	Q16695	633

IntAct

111 interactions, top by confidence:

A	B	Type	Score
EZH2	PHF1	psi-mi:“MI:0914”(association)	0.900
RBBP4	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
EZH2	EPOP	psi-mi:“MI:0914”(association)	0.730
PHF19	EED	psi-mi:“MI:0914”(association)	0.730
SUZ12	EPOP	psi-mi:“MI:0914”(association)	0.640
LCOR	PHF1	psi-mi:“MI:0914”(association)	0.640
PHF19	POTEB3	psi-mi:“MI:0915”(physical association)	0.560
HOXB5	PHF19	psi-mi:“MI:0915”(physical association)	0.560
CSNK2A1	PHF19	psi-mi:“MI:0915”(physical association)	0.560
THAP7	PHF19	psi-mi:“MI:0915”(physical association)	0.560
PHF19	ZNF837	psi-mi:“MI:0915”(physical association)	0.560
PHF19	THAP1	psi-mi:“MI:0915”(physical association)	0.560
PHF19	PICK1	psi-mi:“MI:0915”(physical association)	0.560
PHF19	DVL3	psi-mi:“MI:0915”(physical association)	0.560
PHF19	ZRANB1	psi-mi:“MI:0915”(physical association)	0.560
PHF19	INO80E	psi-mi:“MI:0915”(physical association)	0.560
	PHF19	psi-mi:“MI:0915”(physical association)	0.560
BAG4	PHF19	psi-mi:“MI:0915”(physical association)	0.560
PHF19	SNIP1	psi-mi:“MI:0915”(physical association)	0.560
PHF19	RCOR3	psi-mi:“MI:0915”(physical association)	0.560
POTEB3	PHF19	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (154): PHF19 (Affinity Capture-MS), PHF19 (Affinity Capture-MS), HIST1H3A (Co-crystal Structure), SUZ12 (Affinity Capture-Western), EZH2 (Affinity Capture-Western), EED (Affinity Capture-Western), RBBP7 (Affinity Capture-MS), RBBP4 (Affinity Capture-MS), SUZ12 (Affinity Capture-MS), EZH2 (Affinity Capture-MS), EED (Affinity Capture-MS), HIST1H3A (Protein-peptide), QRICH1 (Affinity Capture-MS), DCTN3 (Affinity Capture-MS), RANGRF (Affinity Capture-MS)

ESM2 similar proteins: A0MTF4, A4Q9F4, M3X9S6, O15520, O35565, O43189, O43320, O54693, O54769, O73754, O95750, P05524, P08620, P11487, P12034, P15656, P31371, P36364, P36386, P48801, P48802, P48803, P48804, P48807, P54130, P70492, P97401, P98172, Q20FD0, Q2HXK8, Q3ZFI5, Q5RF67, Q5T6S3, Q5XI70, Q91875, Q92765, Q92838, Q95117, Q95L12, Q96GD3

Diamond homologs: O43189, Q02395, Q0V9U1, Q24459, Q32LL5, Q5R7T9, Q5RCV7, Q5T6S3, Q68FR3, Q6DJM6, Q6IQU7, Q8WNV2, Q96CB8, Q9CXG9, Q9D168, Q9VBB3, Q9Y483, Q9Z1B8, P87233, Q09908, Q54DV0, O60070, Q8CID0, Q9H8E8, Q6IE82, Q7YZH1, Q7ZVP1, Q92613

SIGNOR signaling

0 interactions.

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
Transcriptional Regulation by E2F6	6	51.7×	8e-08
PKMTs methylate histone lysines	8	37.9×	5e-09
Regulation of PTEN gene transcription	7	36.7×	5e-08
PRC2 methylates histones and DNA	8	35.8×	5e-09
Defective pyroptosis	6	27.6×	3e-06
Negative Regulation of CDH1 Gene Transcription	7	24.8×	5e-07
Regulation of PD-L1(CD274) transcription	6	19.2×	2e-05
Activation of anterior HOX genes in hindbrain development during early embryogenesis	6	16.1×	5e-05

GO biological processes:

GO term	Partners	Fold	FDR
chromatin organization	6	13.5×	3e-04
chromatin remodeling	5	8.3×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	45
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2548 predictions. Top by Δscore:

Variant	Effect	Δscore
9:120858283:CCAT:C	acceptor_gain	1.0000
9:120858284:CAT:C	acceptor_gain	1.0000
9:120858284:CATC:C	acceptor_gain	1.0000
9:120858285:ATCT:A	acceptor_loss	1.0000
9:120858286:TCTGT:T	acceptor_loss	1.0000
9:120858287:C:CC	acceptor_gain	1.0000
9:120858287:C:CG	acceptor_loss	1.0000
9:120858293:C:CT	acceptor_gain	1.0000
9:120858294:A:T	acceptor_gain	1.0000
9:120858298:G:C	acceptor_gain	1.0000
9:120861170:TCACT:T	acceptor_gain	1.0000
9:120861171:CACT:C	acceptor_gain	1.0000
9:120861171:CACTC:C	acceptor_gain	1.0000
9:120861173:CT:C	acceptor_gain	1.0000
9:120861174:TC:T	acceptor_loss	1.0000
9:120861175:C:CC	acceptor_gain	1.0000
9:120861175:C:T	acceptor_loss	1.0000
9:120861176:T:A	acceptor_loss	1.0000
9:120861184:C:CT	acceptor_gain	1.0000
9:120861185:A:T	acceptor_gain	1.0000
9:120861917:CA:C	donor_gain	1.0000
9:120862602:T:TA	donor_gain	1.0000
9:120862611:A:AC	donor_gain	1.0000
9:120862612:C:CC	donor_gain	1.0000
9:120862612:CG:C	donor_gain	1.0000
9:120862612:CGCAG:C	donor_gain	1.0000
9:120862616:G:C	donor_gain	1.0000
9:120862671:C:A	donor_gain	1.0000
9:120864048:CCGG:C	donor_gain	1.0000
9:120864060:A:C	donor_gain	1.0000

AlphaMissense

3786 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:120857965:C:A	W574C	1.000
9:120857965:C:G	W574C	1.000
9:120857967:A:G	W574R	1.000
9:120857967:A:T	W574R	1.000
9:120862684:G:T	P345H	1.000
9:120862687:G:C	P344R	1.000
9:120862687:G:T	P344Q	1.000
9:120862707:G:C	F337L	1.000
9:120862707:G:T	F337L	1.000
9:120862708:A:G	F337S	1.000
9:120862709:A:G	F337L	1.000
9:120862738:C:A	G327V	1.000
9:120862738:C:T	G327D	1.000
9:120862739:C:G	G327R	1.000
9:120862746:G:C	F324L	1.000
9:120862746:G:T	F324L	1.000
9:120862747:A:C	F324C	1.000
9:120862747:A:G	F324S	1.000
9:120862748:A:G	F324L	1.000
9:120864067:A:G	L317P	1.000
9:120864067:A:T	L317Q	1.000
9:120865775:A:G	Y279H	1.000
9:120865807:A:G	L268P	1.000
9:120865813:A:G	L266P	1.000
9:120866029:A:G	W260R	1.000
9:120866029:A:T	W260R	1.000
9:120866042:C:A	R255S	1.000
9:120866042:C:G	R255S	1.000
9:120866043:C:A	R255M	1.000
9:120866043:C:G	R255T	1.000

dbSNP variants (sampled 300 via entrez): RS1000003379 (9:120856929 G>A), RS1000025037 (9:120900435 T>C), RS1000062130 (9:120868885 G>A,T), RS1000075722 (9:120875693 A>G,T), RS1000174812 (9:120894994 C>A), RS1000226249 (9:120874243 G>A), RS1000231413 (9:120891916 A>G,T), RS1000274498 (9:120893552 C>G), RS1000436109 (9:120863101 G>A), RS1000437976 (9:120856466 T>C), RS1000519243 (9:120879910 C>T), RS1000558814 (9:120876042 G>A,C), RS1000611095 (9:120875772 C>T), RS1000616524 (9:120898249 T>C,G), RS1000635413 (9:120879563 A>G)

Disease associations

OMIM: gene MIM:609740 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST004093_7	Prostate-specific antigen levels	4.000000e-09
GCST004278_84	Pulse pressure	3.000000e-06
GCST005038_131	Allergic disease (asthma, hay fever or eczema)	5.000000e-09
GCST005146_36	Birth weight	5.000000e-09
GCST005803_8	Corneal astigmatism	6.000000e-06
GCST006005_5	High density lipoprotein cholesterol levels	2.000000e-08
GCST006230_5	Pulse pressure	2.000000e-07
GCST008362_189	Birth weight	2.000000e-14
GCST010002_279	Refractive error	2.000000e-11

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement
EFO:0004344	birth weight
EFO:1002040	Corneal astigmatism
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5465318 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.31	IC50	4900	nM	CHEMBL6174318
5.29	IC50	5090	nM	CHEMBL6170209

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	5
Valproic Acid	affects expression, decreases expression, decreases methylation, increases expression	5
bisphenol A	decreases expression	2
(+)-JQ1 compound	decreases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Arsenic	affects cotreatment, decreases expression, increases abundance, increases expression	2
Estradiol	decreases expression, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Tretinoin	decreases expression, increases expression	2
GSK-J4	decreases expression	1
bisphenol F	decreases methylation, affects cotreatment	1
dicrotophos	increases expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
propionaldehyde	decreases expression	1
trichostatin A	affects expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
beryllium sulfate	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
indeno(1,2,3-cd)pyrene	decreases expression	1
diallyl trisulfide	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
phenethyl isothiocyanate	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
CHEMBL5373008	Binding	Displacement of Biotin-p53K381acK382me2 from PHF19 (unknown origin) by TR-FRET assay	Discovery of a 53BP1 Small Molecule Antagonist Using a Focused DNA-Encoded Library Screen. — J Med Chem

Clinical trials (associated diseases)

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