PFN2

Summary

PFN2 (profilin 2, HGNC:8882) is a protein-coding gene on chromosome 3q25.1, encoding Profilin-2 (P35080). Binds to actin and affects the structure of the cytoskeleton.

The protein encoded by this gene is a ubiquitous actin monomer-binding protein belonging to the profilin family. It is thought to regulate actin polymerization in response to extracellular signals. There are two alternatively spliced transcript variants encoding different isoforms described for this gene.

Source: NCBI Gene 5217 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 13 total
• Druggable target: yes
• MANE Select transcript: NM_053024

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8882
Approved symbol	PFN2
Name	profilin 2
Location	3q25.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000070087
Ensembl biotype	protein_coding
OMIM	176590
Entrez	5217

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 15 protein_coding, 3 nonsense_mediated_decay, 1 retained_intron

ENST00000239940, ENST00000423691, ENST00000452853, ENST00000460404, ENST00000461868, ENST00000461930, ENST00000468323, ENST00000475518, ENST00000481275, ENST00000481767, ENST00000489155, ENST00000490975, ENST00000494827, ENST00000497060, ENST00000497148, ENST00000498169, ENST00000498307, ENST00000649949, ENST00000936189

RefSeq mRNA: 2 — MANE Select: NM_053024 NM_002628, NM_053024

CCDS: CCDS3148, CCDS46934

Canonical transcript exons

ENST00000239940 — 3 exons

Exon	Start	End
ENSE00001008396	149964904	149966586
ENSE00001881955	149970725	149970895
ENSE00003459196	149968358	149968550

Expression profiles

Bgee: expression breadth ubiquitous, 300 present calls, max score 99.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 126.6217 / max 1019.1066, expressed in 1548 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
45078	102.5089	1536
45079	18.9135	1384
45081	2.2303	1043
45080	2.2206	1049
45076	0.4611	257
45077	0.2334	70
45087	0.0539	40

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
frontal pole	UBERON:0002795	99.65	gold quality
superior frontal gyrus	UBERON:0002661	99.62	gold quality
postcentral gyrus	UBERON:0002581	99.60	gold quality
parietal lobe	UBERON:0001872	99.59	gold quality
Brodmann (1909) area 10	UBERON:0013541	99.55	gold quality
pons	UBERON:0000988	99.54	gold quality
prefrontal cortex	UBERON:0000451	99.53	gold quality
middle temporal gyrus	UBERON:0002771	99.52	gold quality
orbitofrontal cortex	UBERON:0004167	99.51	gold quality
cortical plate	UBERON:0005343	99.49	gold quality
ganglionic eminence	UBERON:0004023	99.48	gold quality
gluteal muscle	UBERON:0002000	99.42	gold quality
ventricular zone	UBERON:0003053	99.40	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.39	gold quality
embryo	UBERON:0000922	99.38	gold quality
cerebellar vermis	UBERON:0004720	99.38	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.38	gold quality
Brodmann (1909) area 46	UBERON:0006483	99.36	gold quality
frontal cortex	UBERON:0001870	99.35	gold quality
superior vestibular nucleus	UBERON:0007227	99.32	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.30	gold quality
cerebral cortex	UBERON:0000956	99.29	gold quality
neocortex	UBERON:0001950	99.27	gold quality
entorhinal cortex	UBERON:0002728	99.25	gold quality
CA1 field of hippocampus	UBERON:0003881	99.24	gold quality
Ammon’s horn	UBERON:0001954	99.22	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.21	gold quality
occipital lobe	UBERON:0002021	99.19	gold quality
temporal lobe	UBERON:0001871	99.15	gold quality
telencephalon	UBERON:0001893	99.15	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-HCAD-10	yes	50.32
E-HCAD-5	yes	27.79
E-GEOD-84465	yes	24.37
E-MTAB-5061	yes	16.88
E-CURD-112	yes	15.86
E-MTAB-9388	yes	15.06
E-MTAB-8271	yes	8.86
E-GEOD-83139	yes	8.46
E-MTAB-8894	no	2530.23
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

136 targeting PFN2, 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-3120-5P	100.00	65.56	965
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-371A-3P	99.99	66.77	91
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-526B-3P	99.88	74.06	2587
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

Literature-anchored findings (GeneRIF, showing 30)

• These findings raise the possibility that Rgl3 mediates interaction between Ras/Rap-family proteins and profilin II, an important activator of actin polymerization. (PMID:17382517)
• A signaling pathway from ROCK1 to profilin controls polyglutamine protein aggregation. (PMID:18573880)
• Oral squamous cell carcinomas with weak PFN2 expression were associated with a significantly worse prognosis than strongly expressed tumours. (PMID:21725608)
• effects of profilin-1 and profilin-2, the two major isoforms of profilin, on actin cytoskeletal regulation, motility, and invasion of breast cancer cells (PMID:23827010)
• Therefore, this study indicates that profilin 2 affects the metastatic potential and stemness of colorectal CSCs by regulating EMT- and stemness-related proteins. (PMID:25964982)
• Pfn2 suppresses the recruitment of HDAC1 to Smad2 and Smad3 promoters, increasing their expression, and, in turn, enhancing TGFB1 induced epithelial-mesenchymal transformation and VEGF and CTGF production. (PMID:26354229)
• Disease causing mutations in inverted formin 2 regulate its binding to G-actin, F-actin capping protein (CapZ alpha-1) and profilin 2. (PMID:26764407)
• PFN2 has a novel role in promoting Esophageal squamous cell carcinoma progression and metastasis. (PMID:27188458)
• Study demonstrated that miR30a inhibits epithelial-mesenchymal transition (EMT) and invasion in highly invasive non-small cell lung cancer (NSCLC) cell lines via targeting PFN2 suggesting that miR30a with PFN2 may play an essential role in the development of NSCLC by modulating EMT and cell invasion. (PMID:28405690)
• Data suggest 2 major isoforms of profilin (Pfn1 and Pfn2) are co-regulated by a common mechanism involving the action of MKL1 [megakaryoblastic leukemia (translocation) 1 protein] that is independent of its SRF- (serum-response factor)-related activity; cellular externalization of Pfn1, rather than transcription, is affected by the perturbations of MKL1; MKL1 can influence cell migration by modulating Pfn1 expression. (PMID:28546428)
• High PFN2 expression might serve as a valuable predictor for poor overall survival of HNSC. DNA amplification and hypomethylation might be two mechanisms of PFN2 dysregulation. (PMID:29322815)
• We unveil PFN2 and GAMT as molecular determinants of Charcot-Marie-Tooth type 2 neuropathy, with possible indications of the role of PFN2 in the pathogenesis and disease progression. (PMID:29449460)
• PFN2 gene, related to regulation of actin cytoskeleton in protein complex F, might play momentous roles in the initiation and development of consecutive Trauma-Induced Sepsis. (PMID:29642183)
• Study indicated that PFN2 may function as a negative regulator of colorectal cancer (CRC) metastasis and, thus, may represent a potential target for CRC therapy. (PMID:30015842)
• Pfn2 levels, regulated by cIAP1, affected intracellular levels of reactive oxygen species. (PMID:30352681)
• Profilin 2 (PFN2) expression is significantly upregulated in Breast cancer (BC) tissues. The abnormal upregulation of PFN2 is associated with poor prognosis in patients with BC. Long noncoding RNA FOXD2 adjacent opposite strand RNA 1 and PFN2 expression is positively correlated. (PMID:30628646)
• Results suggest that PFN2 promotes the proliferation and metastasis of HNSC by activating the PI3K/Akt/beta-catenin signaling pathway. (PMID:31122311)
• hPIV-2 V protein promotes F-actin formation by affecting actin-profilin2 interaction through its binding to profilin2. (PMID:31150988)
• Long non-coding RNA TUG1 regulates the progression and metastasis of osteosarcoma cells via miR-140-5p/PFN2 axis. (PMID:31799645)
• Profilin2a-phosphorylation as a regulatory mechanism for actin dynamics. (PMID:31908005)
• MicroRNA-dependent inhibition of PFN2 orchestrates ERK activation and pluripotent state transitions by regulating endocytosis. (PMID:32788350)
• PFN2 and NAA80 cooperate to efficiently acetylate the N-terminus of actin. (PMID:32978259)
• Profilin 2 (PFN2) promotes the proliferation, migration, invasion and epithelial-to-mesenchymal transition of triple negative breast cancer cells. (PMID:33047272)
• Profilin 2 promotes growth, metastasis, and angiogenesis of small cell lung cancer through cancer-derived exosomes. (PMID:33234737)
• ets1 associates with KMT5A to participate in high glucose-mediated EndMT via upregulation of PFN2 expression in diabetic nephropathy. (PMID:34238215)
• [Profilin 2 is highly expressed in gastric cancer and promotes tumor cell proliferation and migration]. (PMID:35365445)
• OCT1-target neural gene PFN2 promotes tumor growth in androgen receptor-negative prostate cancer. (PMID:35413990)
• MiR-200b-3p is upregulated in the placental tissues from patients with preeclampsia and promotes the development of preeclampsia via targeting profilin 2. (PMID:35613309)
• ELAVL4 promotes the tumorigenesis of small cell lung cancer by stabilizing LncRNA LYPLAL1-DT and enhancing profilin 2 activation. (PMID:37676718)
• Oncogenic circ-SLC16A1 promotes progression of non-small cell lung cancer via regulation of the miR-1287-5p/profilin 2 axis. (PMID:38539084)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pfn2b	ENSDARG00000003952
danio_rerio	pfn2a	ENSDARG00000012682
mus_musculus	Pfn2	ENSMUSG00000027805
rattus_norvegicus	Pfn2	ENSRNOG00000017427

Paralogs (2): PFN1 (ENSG00000108518), PFN3 (ENSG00000196570)

Protein

Protein identifiers

Profilin-2 — P35080 (reviewed: P35080)

Alternative names: Profilin II

All UniProt accessions (8): P35080, C9J0J7, C9J2N0, C9J5V8, C9J712, C9JQ45, F2Z3G0, G5E9Q6

UniProt curated annotations — full annotation on UniProt →

Function. Binds to actin and affects the structure of the cytoskeleton. At high concentrations, profilin prevents the polymerization of actin, whereas it enhances it at low concentrations. By binding to PIP2, it inhibits the formation of IP3 and DG.

Subunit / interactions. Occurs in many kinds of cells as a complex with monomeric actin in a 1:1 ratio. Interacts with PFN2. Interacts with ACTMAP (via N-terminus); the interaction may facilitate efficient cleavage of the acetylated N-terminus of immature actin by ACTMAP. Interacts with ACTMAP (via N-terminus); the interaction may facilitate efficient cleavage of the acetylated N-terminus of immature actin by ACTMAP.

Subcellular location. Cytoplasm. Cytoskeleton.

Tissue specificity. Highly expressed in brain, skeletal muscle and kidney and less strongly in heart, placenta, lung and liver.

Similarity. Belongs to the profilin family.

Isoforms (2)

UniProt ID	Names	Canonical?
P35080-1	IIa	yes
P35080-2	IIb

RefSeq proteins (2): NP_002619, NP_444252* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005454	Profilin1/2/3_vertebrate	Family
IPR005455	PFN_euk	Family
IPR027310	Profilin_CS	Conserved_site
IPR036140	PFN_sf	Homologous_superfamily
IPR048278	PFN	Family

Pfam: PF00235

UniProt features (19 total): strand 9, helix 5, initiator methionine 1, chain 1, modified residue 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1D1J	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35080-F1	95.62	0.92

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 (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-376176	Signaling by ROBO receptors
R-HSA-5663220	RHO GTPases Activate Formins

MSigDB gene sets: 443 (showing top): GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, FAELT_B_CLL_WITH_VH_REARRANGEMENTS_DN, TGCACTT_MIR519C_MIR519B_MIR519A, TTTGTAG_MIR520D, GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_REGULATION_OF_EPITHELIAL_CELL_MIGRATION, GOBP_REGULATION_OF_EXOCYTOSIS, GOBP_REGULATION_OF_RUFFLE_ASSEMBLY, MCBRYAN_PUBERTAL_TGFB1_TARGETS_DN, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT

GO Biological Process (15): negative regulation of epithelial cell migration (GO:0010633), actin cytoskeleton organization (GO:0030036), regulation of actin filament polymerization (GO:0030833), positive regulation of actin filament polymerization (GO:0030838), positive regulation of actin filament bundle assembly (GO:0032233), protein stabilization (GO:0050821), positive regulation of stress fiber assembly (GO:0051496), modification of postsynaptic actin cytoskeleton (GO:0098885), presynaptic actin cytoskeleton organization (GO:0099140), presynaptic modulation of chemical synaptic transmission (GO:0099171), negative regulation of ruffle assembly (GO:1900028), regulation of synaptic vesicle exocytosis (GO:2000300), positive regulation of peptidyl-serine phosphorylation (GO:0033138), modulation of chemical synaptic transmission (GO:0050804), regulation of actin filament organization (GO:0110053)

GO Molecular Function (5): actin binding (GO:0003779), actin monomer binding (GO:0003785), phosphatidylinositol-4,5-bisphosphate binding (GO:0005546), ATP hydrolysis activity (GO:0016887), protein binding (GO:0005515)

GO Cellular Component (8): cytoplasm (GO:0005737), cytoskeleton (GO:0005856), extracellular exosome (GO:0070062), Schaffer collateral - CA1 synapse (GO:0098685), presynapse (GO:0098793), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Axon guidance	1
RHO GTPase Effectors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
synapse	4
actin filament polymerization	2
positive regulation of cytoskeleton organization	2
positive regulation of supramolecular fiber organization	2
epithelial cell migration	1
regulation of epithelial cell migration	1
negative regulation of cell migration	1
negative regulation of multicellular organismal process	1
cytoskeleton organization	1
actin filament-based process	1
regulation of actin polymerization or depolymerization	1
regulation of protein polymerization	1
regulation of actin filament polymerization	1
positive regulation of protein polymerization	1
regulation of actin filament bundle assembly	1
positive regulation of cellular component biogenesis	1
actin filament bundle assembly	1
regulation of protein stability	1
positive regulation of actin filament bundle assembly	1
stress fiber assembly	1
regulation of stress fiber assembly	1
modification of postsynaptic structure	1
actin cytoskeleton organization	1
presynaptic cytoskeleton organization	1
modulation of chemical synaptic transmission	1
presynapse	1
ruffle assembly	1
negative regulation of plasma membrane bounded cell projection assembly	1
regulation of ruffle assembly	1
synaptic vesicle exocytosis	1
regulation of neurotransmitter secretion	1
regulation of regulated secretory pathway	1
positive regulation of protein phosphorylation	1
peptidyl-serine phosphorylation	1
regulation of peptidyl-serine phosphorylation	1
chemical synaptic transmission	1
regulation of trans-synaptic signaling	1
actin filament organization	1
regulation of actin cytoskeleton organization	1

Protein interactions and networks

STRING

1660 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PFN2	HDAC1	Q13547	786
PFN2	ARPC1A	Q92747	785
PFN2	VASP	P50552	724
PFN2	SHMT1	P34896	658
PFN2	WASL	O00401	586
PFN2	RALA	P11233	563
PFN2	CLRN1	P58418	543
PFN2	DNM1	Q05193	539
PFN2	RRAS	P10301	521
PFN2	AKT1	P31749	508
PFN2	ARPC2	O15144	495
PFN2	USP9X	Q93008	495
PFN2	PPP1R1B	Q9UD71	476
PFN2	GPHN	Q9NQX3	474
PFN2	RAP1A	P10113	473

IntAct

91 interactions, top by confidence:

A	B	Type	Score
SMN1	GEMIN2	psi-mi:“MI:0914”(association)	0.960
NS	PIK3R2	psi-mi:“MI:0914”(association)	0.750
VASP	CEP43	psi-mi:“MI:0914”(association)	0.740
PFN2	HTT	psi-mi:“MI:0915”(physical association)	0.700
HTT	PFN2	psi-mi:“MI:0915”(physical association)	0.700
Wasl	PFN2	psi-mi:“MI:0914”(association)	0.600
Wasl	PFN2	psi-mi:“MI:0407”(direct interaction)	0.600
DNALI1	GSN	psi-mi:“MI:0914”(association)	0.510
GOLGB1	PFN2	psi-mi:“MI:0915”(physical association)	0.510
WASF1	PFN2	psi-mi:“MI:0915”(physical association)	0.400
MUC7	PFN2	psi-mi:“MI:0915”(physical association)	0.370
PFN2	MSANTD3	psi-mi:“MI:0915”(physical association)	0.370
OTUB1		psi-mi:“MI:0914”(association)	0.350
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
TK	AP3B1	psi-mi:“MI:0914”(association)	0.350
	IPO5	psi-mi:“MI:0914”(association)	0.350
E6	TRAFD1	psi-mi:“MI:0914”(association)	0.350
E6	PLOD2	psi-mi:“MI:0914”(association)	0.350
MAD2L2		psi-mi:“MI:0914”(association)	0.350
DLD	NFKBIE	psi-mi:“MI:0914”(association)	0.350
DLD	IRS4	psi-mi:“MI:0914”(association)	0.350
GRN	OPA1	psi-mi:“MI:0914”(association)	0.350
KDM6B	PFN2	psi-mi:“MI:0914”(association)	0.350
ZDHHC5	HACD3	psi-mi:“MI:0914”(association)	0.350

BioGRID (187): FHOD1 (Two-hybrid), PFN2 (Affinity Capture-MS), PFN2 (Affinity Capture-MS), NAT6 (Affinity Capture-MS), INF2 (Affinity Capture-MS), PALLD (Affinity Capture-MS), ACTBL2 (Affinity Capture-MS), ACTA2 (Affinity Capture-MS), ACTB (Affinity Capture-MS), DIAPH1 (Affinity Capture-MS), BLVRB (Affinity Capture-MS), ENAH (Affinity Capture-MS), VASP (Affinity Capture-MS), PFN2 (Affinity Capture-MS), PFN2 (Affinity Capture-MS)

ESM2 similar proteins: A4GCR5, A4GCR7, A4GCR8, A4GD50, A4GD54, A4GDQ8, A4GDR9, A4GDT3, A4GE38, A4GE39, A4KA54, A4KA61, A7RT29, A7S6M8, A9UMU8, D3ZVF4, P02584, P06625, P07737, P08240, P35080, P38334, P62962, P62963, Q08CN0, Q09430, Q0P3X8, Q0VGL1, Q29EZ6, Q29NZ8, Q2M2U3, Q2NKT1, Q3MHE8, Q4PM15, Q4R4P8, Q4S4I5, Q54DY3, Q54QW5, Q5IRJ7, Q5R483

Diamond homologs: M0RCP6, P02584, P07737, P35080, P60673, P62962, P62963, Q09430, Q32PB1, Q4R4P8, Q5R4E2, Q9DAD6, Q9EPC6, Q9JJV2, A0A7H0DND9, O57243, P0DSW5, P0DSW6, P68695, Q6RZE1, Q76ZN5, Q775N7, Q77DS0, Q77TH1, Q80DT4, Q8JL78, Q8V2L6, Q8V4T7

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 86 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
FCGR3A-mediated phagocytosis	5	13.8×	5e-03
Regulation of actin dynamics for phagocytic cup formation	5	13.5×	5e-03
Translocation of SLC2A4 (GLUT4) to the plasma membrane	5	11.3×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	7
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1036 predictions. Top by Δscore:

Variant	Effect	Δscore
3:149968355:CACC:C	donor_loss	1.0000
3:149968356:A:T	donor_loss	1.0000
3:149968562:C:CT	acceptor_gain	1.0000
3:149968563:A:T	acceptor_gain	1.0000
3:149970719:CCTCA:C	donor_loss	1.0000
3:149970720:CTCA:C	donor_loss	1.0000
3:149970721:TCAC:T	donor_loss	1.0000
3:149970722:CA:C	donor_loss	1.0000
3:149970723:A:AC	donor_gain	1.0000
3:149970724:C:CC	donor_gain	1.0000
3:149966273:C:CT	acceptor_gain	0.9900
3:149966276:A:T	acceptor_gain	0.9900
3:149966473:A:C	donor_gain	0.9900
3:149968357:CCT:C	donor_gain	0.9900
3:149968559:C:T	acceptor_gain	0.9900
3:149968562:C:T	acceptor_gain	0.9900
3:149966275:C:CT	acceptor_gain	0.9800
3:149966587:C:CC	acceptor_gain	0.9800
3:149968356:A:AC	donor_gain	0.9800
3:149968357:C:CC	donor_gain	0.9800
3:149968550:GC:G	acceptor_loss	0.9800
3:149968551:C:CC	acceptor_gain	0.9800
3:149968559:C:CT	acceptor_gain	0.9800
3:149966582:CAAGA:C	acceptor_gain	0.9700
3:149968352:A:AC	donor_gain	0.9700
3:149968353:C:CC	donor_gain	0.9700
3:149968496:C:CT	acceptor_gain	0.9700
3:149968547:TTGG:T	acceptor_gain	0.9700
3:149968549:GG:G	acceptor_gain	0.9700
3:149971422:G:GT	donor_gain	0.9700

AlphaMissense

918 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:149966508:A:G	L135S	1.000
3:149966537:A:C	N125K	1.000
3:149966537:A:T	N125K	1.000
3:149966547:C:T	G122D	1.000
3:149966550:C:T	G121E	1.000
3:149966568:C:A	G115V	1.000
3:149966568:C:T	G115E	1.000
3:149966569:C:G	G115R	1.000
3:149966569:C:T	G115R	1.000
3:149966580:A:T	V111D	1.000
3:149968372:C:T	G104D	1.000
3:149968375:A:T	V103D	1.000
3:149968383:A:C	N100K	1.000
3:149968383:A:T	N100K	1.000
3:149968410:C:A	K91N	1.000
3:149968410:C:G	K91N	1.000
3:149968412:T:C	K91E	1.000
3:149968417:C:G	R89P	1.000
3:149968422:G:C	D87E	1.000
3:149968422:G:T	D87E	1.000
3:149968423:T:A	D87V	1.000
3:149968423:T:C	D87G	1.000
3:149968423:T:G	D87A	1.000
3:149968424:C:A	D87Y	1.000
3:149968424:C:G	D87H	1.000
3:149968456:T:A	D76V	1.000
3:149968456:T:G	D76A	1.000
3:149968457:C:G	D76H	1.000
3:149968458:T:A	R75S	1.000
3:149968458:T:G	R75S	1.000

dbSNP variants (sampled 300 via entrez): RS1001019125 (3:149971732 A>C), RS1001533617 (3:149972075 A>G), RS1001692797 (3:149970073 T>C), RS1002136514 (3:149971250 G>A), RS1002185213 (3:149965520 T>A), RS1002204428 (3:149970255 A>C,G), RS1002301099 (3:149965156 A>G,T), RS1002396255 (3:149970232 G>A,C), RS1002424942 (3:149971146 T>A,C,G), RS1003228762 (3:149971758 A>G,T), RS1003829053 (3:149965756 T>C), RS1004128196 (3:149970995 C>A,T), RS1004929526 (3:149972332 T>A), RS1005042726 (3:149972839 G>C,T), RS1005600597 (3:149970464 C>A)

Disease associations

OMIM: gene MIM:176590 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010142_40	Fish- and plant-related diet	1.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008111	diet measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725166 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	5
Particulate Matter	affects cotreatment, increases expression, decreases expression, increases abundance	3
bisphenol A	decreases expression, increases expression	2
trichostatin A	increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	2
Fluorouracil	increases expression, affects response to substance, affects reaction, decreases expression	2
Cyclosporine	increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
beta-Naphthoflavone	increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression, increases expression	1
decabromobiphenyl ether	decreases expression	1
sodium arsenite	affects binding, increases reaction	1
tetrabromobisphenol A	decreases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	increases expression	1
perfluorooctanoic acid	increases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol B	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	increases expression	1
LDN 193189	increases expression, affects cotreatment	1
bisphenol AF	increases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Acetaminophen	decreases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697413	Binding	Inhibition of PFN2 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C0BK	Abcam HeLa PFN2 KO	Cancer cell line	Female
CVCL_TC98	HAP1 PFN2 (-) 1	Cancer cell line	Male
CVCL_XR55	HAP1 PFN2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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