PHF1

Summary

PHF1 (PHD finger protein 1, HGNC:8919) is a protein-coding gene on chromosome 6p21.32, encoding PHD finger protein 1 (O43189). Polycomb group (PcG) that specifically binds histone H3 trimethylated at ‘Lys-36’ (H3K36me3) and recruits the PRC2 complex.

This gene encodes a Polycomb group protein. The protein is a component of a histone H3 lysine-27 (H3K27)-specific methyltransferase complex, and functions in transcriptional repression of homeotic genes. The protein is also recruited to double-strand breaks, and reduced protein levels results in X-ray sensitivity and increased homologous recombination. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 5252 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 73 total
• Druggable target: yes
• MANE Select transcript: NM_024165

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8919
Approved symbol	PHF1
Name	PHD finger protein 1
Location	6p21.32
Locus type	gene with protein product
Status	Approved
Aliases	MTF2L2, TDRD19C, PCL1
Ensembl gene	ENSG00000112511
Ensembl biotype	protein_coding
OMIM	602881
Entrez	5252

Gene structure

Transcript identifiers

Ensembl transcripts: 39 — 32 protein_coding, 4 nonsense_mediated_decay, 3 retained_intron

ENST00000374512, ENST00000374516, ENST00000427004, ENST00000427826, ENST00000428274, ENST00000459809, ENST00000479029, ENST00000486845, ENST00000487667, ENST00000488767, ENST00000495509, ENST00000859000, ENST00000859001, ENST00000859002, ENST00000859003, ENST00000859004, ENST00000859005, ENST00000859006, ENST00000859007, ENST00000859008, ENST00000859009, ENST00000859010, ENST00000859011, ENST00000859012, ENST00000859013, ENST00000859014, ENST00000859015, ENST00000927500, ENST00000927501, ENST00000927502, ENST00000941044, ENST00000941045, ENST00000941046, ENST00000941047, ENST00000941048, ENST00000941049, ENST00000941050, ENST00000941051, ENST00000941052

RefSeq mRNA: 2 — MANE Select: NM_024165 NM_002636, NM_024165

CCDS: CCDS4777, CCDS4778

Canonical transcript exons

ENST00000374516 — 15 exons

Exon	Start	End
ENSE00002240772	33413409	33413557
ENSE00002245273	33414725	33414829
ENSE00002249007	33412698	33412793
ENSE00002264022	33414243	33414366
ENSE00002280829	33413196	33413296
ENSE00002290914	33414041	33414109
ENSE00002294497	33414955	33415144
ENSE00002310484	33412508	33412589
ENSE00003458796	33414477	33414544
ENSE00003542491	33415810	33416439
ENSE00003551956	33415590	33415670
ENSE00003589135	33415235	33415329
ENSE00003734648	33412248	33412422
ENSE00003784857	33413736	33413831
ENSE00003903124	33411014	33411215

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.4647 / max 643.6026, expressed in 1816 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
67287	21.5954	1814
67284	2.2897	952
67283	2.2052	1209
67285	1.0018	309
67286	0.3725	93

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	99.26	gold quality
right testis	UBERON:0004534	99.26	gold quality
pituitary gland	UBERON:0000007	99.07	gold quality
adenohypophysis	UBERON:0002196	99.01	gold quality
left ovary	UBERON:0002119	98.75	gold quality
right ovary	UBERON:0002118	98.51	gold quality
ovary	UBERON:0000992	98.50	gold quality
left lobe of thyroid gland	UBERON:0001120	98.46	gold quality
thyroid gland	UBERON:0002046	98.34	gold quality
right lobe of thyroid gland	UBERON:0001119	98.30	gold quality
endocervix	UBERON:0000458	98.17	gold quality
mucosa of stomach	UBERON:0001199	98.08	gold quality
popliteal artery	UBERON:0002250	98.08	gold quality
tibial artery	UBERON:0007610	98.08	gold quality
testis	UBERON:0000473	97.93	gold quality
prostate gland	UBERON:0002367	97.86	gold quality
fundus of stomach	UBERON:0001160	97.85	gold quality
body of uterus	UBERON:0009853	97.84	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.74	gold quality
left uterine tube	UBERON:0001303	97.72	gold quality
hypothalamus	UBERON:0001898	97.72	gold quality
right coronary artery	UBERON:0001625	97.70	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.59	gold quality
spleen	UBERON:0002106	97.58	gold quality
metanephros cortex	UBERON:0010533	97.57	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.57	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.54	gold quality
lower esophagus	UBERON:0013473	97.53	gold quality
ascending aorta	UBERON:0001496	97.52	gold quality
thoracic aorta	UBERON:0001515	97.52	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.06

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
HOXA10	Repression
HOXA9	Repression

miRNA regulators (miRDB)

62 targeting PHF1, 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-6867-5P	100.00	82.21	3464
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-371A-3P	99.99	66.77	91
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111

Literature-anchored findings (GeneRIF, showing 26)

• The role of PHF1 in H3K27 methylation and Hox gene silencing is reported. (PMID:18086877)
• PHF1 modulates the activity of Ezh2 in favor of the repressive H3K27me3 mark (PMID:18285464)
• PHF1 interacts physically with Ku70/Ku80, suggesting that PHF1 promotes nonhomologous end-joining processes. (PMID:18385154)
• predicted 684-amino acid JAZF1/PHF1 chimeric protein retained one zinc finger domain from JAZF1 and the two zinc finger domains from PHF1, and its oncogenic mechanism should be similar to that of the JAZF1/SUZ12 protein (PMID:18722875)
• The PHF1 gene, previously shown to be the 3’-partner of fusion genes in endometrial stromal tumors, is also recurrently involved in the pathogenesis of ossifying fibromyxoid tumors. (PMID:22796436)
• Morphological features, immunoprofile and fluorescence in situ hybridization rearrangements of JAZF1 and PHF1 genes were correlated with tumor category and outcome in endometrial sarcomas (PMID:22918161)
• findings show that the interaction of Phf19 with H3K36me2 and H3K36me3 is essential for PRC2 complex activity and for proper regulation of gene repression in embryonic stem cells (PMID:23104054)
• findings suggest that PHF1 can mediate deposition of the repressive H3K27me3 mark and acts as a cofactor in early DNA-damage response (PMID:23142980)
• Polycomb group protein PHF1 regulates p53-dependent cell growth arrest and apoptosis (PMID:23150668)
• All endometrial stromal sarcomas showing sex cords had PHF1 genetic rearrangement, suggesting that such rearrangements may induce sex cord differentiation. (PMID:23211293)
• 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)
• PHF1b may be a molecular transducer of GABA A receptor function and thus GABA-mediated neurotransmission in the central nervous system. (PMID:23879974)
• Underscore the likely importance of PHF1 rearrangements in the pathogenesis of ossifying fibromyxoid tumors of soft parts. (PMID:23887158)
• full-length PHF1 in HEK293 cells co-localizes with histone K27me3, but not with K36me3, and this co-localization depends on the trimethyllysine binding pocket indicating that K27me3 is an in vivo target for the PHF1 Tudor domain (PMID:23954330)
• ZC3H7B-BCOR and MEAF6-PHF1 fusions occurred predominantly in S100 protein-negative and malignant OFMT. (PMID:24285434)
• ZC3H7B-BCOR and MEAF6-PHF1 fusions occurred predominantly in S100 protein-negative and malignant ossifying fibromyxoid tumors. (PMID:24285434)
• present two more ESS with MEAF6/PHF1 detected by transcriptome sequencing (case 1) and RT-PCR (case 2), proving that this fusion is recurrent in ESS (PMID:24530230)
• the F61L/S86F mutant of MTF2 Tudor-PHD1 was able to bind to H3K36me3 as strong as the PHF1 Tudor bound to this PTM . We concluded that the hydrophobic patch plays an essential role in binding of these Tudors to methylated chromatin (PMID:25923537)
• PCL1 binds to and stabilizes p53 to induce cellular quiescence (PMID:26494712)
• the increase of DNA accessibility within the H3K36me3-containing nucleosome, instigated by the Tudor domain of PHF1 binding to H3K36me3, is dramatically enhanced by the PHF1 N-terminal domain. (PMID:28082396)
• PHF1 promotes cell proliferation, invasion, and tumorigenesis in vivo and in vitro and its expression is markedly upregulated in a variety of human cancers (PMID:29846670)
• PHF1 fusions cause distinct gene expression and chromatin accessibility profiles in ossifying fibromyxoid tumors and mesenchymal cells. (PMID:31932680)
• A novel MBTD1-PHF1 gene fusion in endometrial stromal sarcoma: A case report and literature review. (PMID:32237188)
• Primary malignant ossifying fibromyxoid tumour of the bone. A clinicopathologic and molecular report of two cases. (PMID:33179613)
• A PHF1-TFE3 fusion atypical ossifying fibromyxoid tumor with prominent collagenous rosettes: Case report with a brief review. (PMID:34560087)
• When molecular outsmarts morphology: Malignant ossifying fibromyxoid tumors masquerading as osteosarcomas, including a novel CREBZF::PHF1 fusion. (PMID:37819540)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	phf1	ENSDARG00000057439
mus_musculus	Phf1	ENSMUSG00000024193
rattus_norvegicus	Phf1	ENSRNOG00000000480
drosophila_melanogaster	Pcl	FBGN0003044

Paralogs (2): PHF19 (ENSG00000119403), MTF2 (ENSG00000143033)

Protein

Protein identifiers

PHD finger protein 1 — O43189 (reviewed: O43189)

Alternative names: Polycomb-like protein 1

All UniProt accessions (8): O43189, A0A087WVG4, A0A1U9X8A3, A2AB22, A2AB23, A2AB25, E9PQT8, E9PQZ5

UniProt curated annotations — full annotation on UniProt →

Function. Polycomb group (PcG) that specifically binds histone H3 trimethylated at ‘Lys-36’ (H3K36me3) and recruits the PRC2 complex. Involved in DNA damage response and is recruited at double-strand breaks (DSBs). Acts by binding to H3K36me3, a mark for transcriptional activation, and recruiting the PRC2 complex: it is however unclear whether recruitment of the PRC2 complex to H3K36me3 leads to enhance or inhibit H3K27me3 methylation mediated by the PRC2 complex. According to some reports, PRC2 recruitment by PHF1 promotes H3K27me3 and subsequent gene silencing by inducing spreading of PRC2 and H3K27me3 into H3K36me3 loci. According to another report, PHF1 recruits the PRC2 complex at double-strand breaks (DSBs) and inhibits the activity of PRC2. Regulates p53/TP53 stability and prolonges its turnover: may act by specifically binding to a methylated from of p53/TP53.

Subunit / interactions. Interacts with CHMP1. Associated component of the PRC2 complex. Interacts with p53/TP53.

Subcellular location. Nucleus. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome.

Tissue specificity. Highest levels in heart, skeletal muscle, and pancreas, lower levels in brain, placenta, lung, liver and kidney.

Disease relevance. A chromosomal aberration involving PHF1 may be a cause of endometrial stromal tumors. Translocation t(6;7)(p21;p22) with JAZF1. Translocation t(1;6)(p34;p21) with MEAF6.

Domain organisation. The Tudor domain recognizes and binds H3K36me3.

Similarity. Belongs to the Polycomblike family.

Isoforms (2)

UniProt ID	Names	Canonical?
O43189-1	2, PHF2	yes
O43189-2	1, PHF1

RefSeq proteins (2): NP_002627, NP_077084* (*=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
IPR031202	PHF1_PDH-finger1	Domain
IPR040477	KDM4-like_Tudor	Domain
IPR047010	PHF1_PHD-finger2	Domain
IPR047399	Tudor_PHF1	Domain

Pfam: PF00628, PF14061, PF18104

UniProt features (62 total): strand 16, helix 13, turn 10, compositionally biased region 5, mutagenesis site 5, region of interest 3, modified residue 2, splice variant 2, sequence variant 2, zinc finger region 2, chain 1, domain 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
6WAV	X-RAY DIFFRACTION	1.7
6WAT	X-RAY DIFFRACTION	1.8
4HCZ	X-RAY DIFFRACTION	1.85
7LKY	X-RAY DIFFRACTION	1.85
5XFN	X-RAY DIFFRACTION	1.9
5XFO	X-RAY DIFFRACTION	1.9
5XFP	X-RAY DIFFRACTION	2.3
8H43	X-RAY DIFFRACTION	2.3
2E5P	SOLUTION NMR
2M0O	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43189-F1	72.53	0.52

Functional residue map

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

Post-translational modifications (2): 420, 360

Mutagenesis-validated functional residues (5):

Position	Phenotype
41	abolishes histone h3k36me3-binding and localization at double-strand breaks (dsbs).
47	abolishes histone h3k36me3-binding.
65	abolishes histone h3k36me3-binding.
66	impairs histone h3k36me3-binding.
71	abolishes histone h3k36me3-binding.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 233 (showing top): AHRARNT_01, ZHAN_MULTIPLE_MYELOMA_PR_DN, TGCGCANK_UNKNOWN, AREB6_03, GGGTGGRR_PAX4_03, AAAYRNCTG_UNKNOWN, CAGCTG_AP4_Q5, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_UP, GOCC_MICROTUBULE_ORGANIZING_CENTER, WANG_ESOPHAGUS_CANCER_VS_NORMAL_DN, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, KESHELAVA_MULTIPLE_DRUG_RESISTANCE, BLALOCK_ALZHEIMERS_DISEASE_UP, GOCC_CENTROSOME, GOBP_DNA_DAMAGE_RESPONSE

GO Biological Process (4): negative regulation of gene expression, epigenetic (GO:0045814), DNA repair-dependent chromatin remodeling (GO:0140861), chromatin organization (GO:0006325), DNA damage response (GO:0006974)

GO Molecular Function (10): transcription corepressor binding (GO:0001222), DNA binding (GO:0003677), chromatin binding (GO:0003682), zinc ion binding (GO:0008270), identical protein binding (GO:0042802), histone H3K4me3 reader activity (GO:0140002), histone H3K36me3 reader activity (GO:0140003), histone methyltransferase binding (GO:1990226), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (8): nucleus (GO:0005634), nucleoplasm (GO:0005654), centrosome (GO:0005813), cytosol (GO:0005829), ESC/E(Z) complex (GO:0035098), site of double-strand break (GO:0035861), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

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
cellular anatomical structure	3
binding	2
histone H3 reader activity	2
negative regulation of gene expression	1
epigenetic regulation of gene expression	1
chromatin remodeling	1
DNA damage response	1
cellular component organization	1
cellular response to stress	1
transcription coregulator binding	1
nucleic acid binding	1
transition metal ion binding	1
protein binding	1
enzyme binding	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
centriole	1
microtubule organizing center	1
cytoplasm	1
PcG protein complex	1
histone methyltransferase complex	1
site of DNA damage	1
intracellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1248 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PHF1	EPOP	A6NHQ4	978
PHF1	EZH2	Q15910	967
PHF1	JARID2	Q92833	958
PHF1	AEBP2	Q6ZN18	942
PHF1	MTF2	Q9Y483	912
PHF1	PHF19	Q5T6S3	899
PHF1	SUZ12	Q15022	886
PHF1	MEAF6	Q9HAF1	828
PHF1	MAPT	P10636	772
PHF1	MBTD1	Q05BQ5	729
PHF1	JAZF1	Q86VZ6	714
PHF1	RBBP7	Q16576	710
PHF1	H3C14	Q71DI3	705
PHF1	EZH1	Q92800	704
PHF1	PHF13	Q86YI8	676

IntAct

256 interactions, top by confidence:

A	B	Type	Score
PHF1	EZH2	psi-mi:“MI:0915”(physical association)	0.900
NAB2	PHF1	psi-mi:“MI:0915”(physical association)	0.780
HSD17B14	PHF1	psi-mi:“MI:0915”(physical association)	0.780
PHF1	HSD17B14	psi-mi:“MI:0915”(physical association)	0.780
PHF1	NAB2	psi-mi:“MI:0915”(physical association)	0.780
EZH2	EPOP	psi-mi:“MI:0914”(association)	0.730
PHF1	TRIM23	psi-mi:“MI:0915”(physical association)	0.670
PHF1	TFCP2	psi-mi:“MI:0915”(physical association)	0.670
PHF1	RBPMS	psi-mi:“MI:0915”(physical association)	0.670
PHF1	BIRC7	psi-mi:“MI:0915”(physical association)	0.670
PHF1	PDLIM7	psi-mi:“MI:0915”(physical association)	0.670
RBPMS	PHF1	psi-mi:“MI:0915”(physical association)	0.670
TFCP2	PHF1	psi-mi:“MI:0915”(physical association)	0.670
TRIM23	PHF1	psi-mi:“MI:0915”(physical association)	0.670
PDLIM7	PHF1	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (293): PHF1 (Two-hybrid), PHF1 (Two-hybrid), TFCP2 (Two-hybrid), PDLIM7 (Two-hybrid), CALCOCO2 (Two-hybrid), RBPMS (Two-hybrid), HSD17B14 (Two-hybrid), VAC14 (Two-hybrid), BIRC7 (Two-hybrid), ATXN7L1 (Two-hybrid), PHF1 (Affinity Capture-MS), PHF1 (Affinity Capture-MS), RBPMS (Two-hybrid), THAP1 (Two-hybrid), PHF1 (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

2 interactions.

A	Effect	B	Mechanism
PHF1	“down-regulates quantity by repression”	HOXA9	“transcriptional regulation”
PHF1	“down-regulates quantity by repression”	HOXA10	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	57
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2017 predictions. Top by Δscore:

Variant	Effect	Δscore
6:33411214:CGGTA:C	donor_loss	1.0000
6:33411216:G:GG	donor_gain	1.0000
6:33411216:GT:G	donor_loss	1.0000
6:33412241:T:TA	acceptor_gain	1.0000
6:33412242:G:A	acceptor_gain	1.0000
6:33412246:A:AG	acceptor_gain	1.0000
6:33412246:AG:A	acceptor_gain	1.0000
6:33412247:G:GG	acceptor_gain	1.0000
6:33412247:GG:G	acceptor_gain	1.0000
6:33412247:GGC:G	acceptor_gain	1.0000
6:33412247:GGCC:G	acceptor_gain	1.0000
6:33412247:GGCCC:G	acceptor_gain	1.0000
6:33412420:AAG:A	donor_gain	1.0000
6:33412420:AAGGT:A	donor_loss	1.0000
6:33412421:AG:A	donor_gain	1.0000
6:33412421:AGGTA:A	donor_loss	1.0000
6:33412422:GG:G	donor_gain	1.0000
6:33412423:G:GG	donor_gain	1.0000
6:33412423:GTA:G	donor_loss	1.0000
6:33412424:T:A	donor_loss	1.0000
6:33412841:G:GT	donor_gain	1.0000
6:33413531:T:G	donor_gain	1.0000
6:33413553:GGGGA:G	donor_gain	1.0000
6:33413554:GGGA:G	donor_gain	1.0000
6:33413554:GGGAG:G	donor_gain	1.0000
6:33413555:G:T	donor_gain	1.0000
6:33413555:GGA:G	donor_gain	1.0000
6:33413555:GGAG:G	donor_gain	1.0000
6:33413556:GA:G	donor_gain	1.0000
6:33413556:GAG:G	donor_gain	1.0000

AlphaMissense

3623 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:33412379:C:A	A39D	1.000
6:33412384:T:A	W41R	1.000
6:33412384:T:C	W41R	1.000
6:33412390:G:C	D43H	1.000
6:33412390:G:T	D43Y	1.000
6:33412391:A:C	D43A	1.000
6:33412391:A:T	D43V	1.000
6:33412393:G:A	G44R	1.000
6:33412393:G:C	G44R	1.000
6:33412393:G:T	G44W	1.000
6:33412394:G:A	G44E	1.000
6:33412394:G:T	G44V	1.000
6:33412397:T:C	L45P	1.000
6:33412402:T:G	Y47D	1.000
6:33412408:G:C	G49R	1.000
6:33412409:G:A	G49D	1.000
6:33412529:T:C	C61R	1.000
6:33412536:T:A	V63D	1.000
6:33412541:T:A	F65I	1.000
6:33412541:T:C	F65L	1.000
6:33412541:T:G	F65V	1.000
6:33412542:T:C	F65S	1.000
6:33412542:T:G	F65C	1.000
6:33412543:T:A	F65L	1.000
6:33412543:T:G	F65L	1.000
6:33412547:G:C	D67H	1.000
6:33412548:A:T	D67V	1.000
6:33412559:T:C	F71L	1.000
6:33412561:T:A	F71L	1.000
6:33412561:T:G	F71L	1.000

dbSNP variants (sampled 300 via entrez): RS1000420976 (6:33408691 A>T), RS1000806306 (6:33410217 C>T), RS1000881131 (6:33412978 G>A), RS1001202102 (6:33414172 C>A), RS1001792307 (6:33413790 C>G,T), RS1002353031 (6:33410997 T>A,C,G), RS1002746274 (6:33412116 T>C), RS1002879087 (6:33412335 C>G,T), RS1003589792 (6:33408573 C>G), RS1003798973 (6:33411067 C>T), RS1003817785 (6:33409579 G>A), RS1003883081 (6:33409336 G>A,T), RS1003886535 (6:33409123 G>A,C), RS1004036561 (6:33415636 G>A,T), RS1004492886 (6:33416085 G>A)

Disease associations

OMIM: gene MIM:602881 | 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
GCST004521_251	Autism spectrum disorder or schizophrenia	6.000000e-12
GCST004521_287	Autism spectrum disorder or schizophrenia	5.000000e-08
GCST004521_75	Autism spectrum disorder or schizophrenia	8.000000e-10
GCST005951_153	Body mass index	5.000000e-09
GCST007656_5	Chronic obstructive pulmonary disease or resting heart rate (pleiotropy)	3.000000e-15
GCST010002_50	Refractive error	4.000000e-34

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6196060 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases expression	5
sodium arsenite	affects expression, increases abundance, increases expression	3
Cyclosporine	increases expression	3
cobaltous chloride	increases expression	2
Benzo(a)pyrene	decreases methylation, increases expression	2
Tobacco Smoke Pollution	increases expression	2
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
geraniol	increases expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
linalool	decreases expression	1
nickel sulfate	increases expression	1
cupric oxide	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	decreases expression, affects cotreatment	1
abrine	increases expression	1
quinocetone	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
NSC 689534	affects binding, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Bortezomib	increases expression	1
Arsenic Trioxide	increases expression	1
Vorinostat	decreases expression	1
Arsenic	increases abundance, increases expression	1
Atrazine	increases expression	1
Vehicle Emissions	affects cotreatment, increases abundance, increases expression, increases response to substance	1
Caffeine	decreases phosphorylation	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
CHEMBL6131007	Binding	Antagonist activity at PHF1 chromodomain (unknown origin) using UNC6957 as substrate measured after 1 hr by TR-FRET assay	Discovery of CHD1 Antagonists for PTEN-Deficient Prostate Cancer. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8MI	Abcam HCT 116 PHF1 KO	Cancer cell line	Male
CVCL_B9A9	Abcam MCF-7 PHF1 KO	Cancer cell line	Female
CVCL_B9PP	Abcam A-549 PHF1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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