PFN3

Summary

PFN3 (profilin 3, HGNC:18627) is a protein-coding gene on chromosome 5q35.3, encoding Profilin-3 (P60673). Binds to actin and affects the structure of the cytoskeleton.

The product of this gene belongs to the profilin family of proteins. This protein binds to actin and affects the structure of the cytoskeleton. It also may be involved in spermatogenesis. It is a single exon gene.

Source: NCBI Gene 345456 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 30 total — 1 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_001029886

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18627
Approved symbol	PFN3
Name	profilin 3
Location	5q35.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000196570
Ensembl biotype	protein_coding
OMIM	612812
Entrez	345456

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000358571

RefSeq mRNA: 1 — MANE Select: NM_001029886 NM_001029886

CCDS: CCDS34301

Canonical transcript exons

ENST00000358571 — 1 exons

Exon	Start	End
ENSE00001410937	177400109	177400661

Expression profiles

Bgee: expression breadth broad, 24 present calls, max score 95.55.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0435 / max 24.8097, expressed in 9 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
65085	0.0223	8
65083	0.0140	3
65084	0.0040	3
65082	0.0033	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	95.55	gold quality
right testis	UBERON:0004534	81.05	gold quality
left testis	UBERON:0004533	80.80	gold quality
testis	UBERON:0000473	78.60	gold quality
adult mammalian kidney	UBERON:0000082	52.53	gold quality
cortical plate	UBERON:0005343	51.80	gold quality
right lobe of liver	UBERON:0001114	46.95	gold quality
kidney	UBERON:0002113	46.31	gold quality
liver	UBERON:0002107	42.67	gold quality
metanephros cortex	UBERON:0010533	40.79	gold quality
cortex of kidney	UBERON:0001225	40.41	gold quality
bone marrow cell	CL:0002092	38.76	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
bone marrow	UBERON:0002371	33.07	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
prefrontal cortex	UBERON:0000451	31.20	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
duodenum	UBERON:0002114	28.14	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	27.98	silver quality
lymph node	UBERON:0000029	27.57	gold quality
leukocyte	CL:0000738	27.42	silver quality
monocyte	CL:0000576	27.40	silver quality
tonsil	UBERON:0002372	27.05	gold quality
frontal cortex	UBERON:0001870	26.96	silver quality
islet of Langerhans	UBERON:0000006	26.55	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.16

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• Porfilin 3 has the actin-binding site conserved, but retains only approximately half of the common poly-L-proline binding site. (PMID:19419568)
• Profilin 3 genetic architecture in glioma formalin fixed paraffin embedded (FFPE) archive. (PMID:33775850)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pfn3	ENSMUSG00000044444
rattus_norvegicus	Pfn3	ENSRNOG00000082948

Paralogs (2): PFN2 (ENSG00000070087), PFN1 (ENSG00000108518)

Protein

Protein identifiers

Profilin-3 — P60673 (reviewed: P60673)

Alternative names: Profilin III

All UniProt accessions (1): P60673

UniProt curated annotations — full annotation on UniProt →

Function. Binds to actin and affects the structure of the cytoskeleton. Slightly reduces actin polymerization. Binds to poly-L-proline, phosphatidylinositol 3-phosphate (PtdIns(3)P), phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and phosphatidylinositol 4-phosphate (PtdIns(4)P). May be involved in spermatogenesis.

Subunit / interactions. Interacts with ACTRT3.

Subcellular location. Cytoplasm. Cytoskeleton. Nucleus.

Tissue specificity. Testis specific.

Similarity. Belongs to the profilin family.

RefSeq proteins (1): NP_001025057* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF00235

UniProt features (1 total): chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P60673-F1	94.41	0.91

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 45 (showing top): GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_ACTIN_FILAMENT_ORGANIZATION, GOBP_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_REGULATION_OF_ACTIN_FILAMENT_BUNDLE_ASSEMBLY, GOMF_ACTIN_BINDING, GOBP_POSITIVE_REGULATION_OF_ACTIN_FILAMENT_BUNDLE_ASSEMBLY, GOBP_REGULATION_OF_CYTOSKELETON_ORGANIZATION, GOBP_REGULATION_OF_ACTIN_FILAMENT_LENGTH, KEGG_REGULATION_OF_ACTIN_CYTOSKELETON

GO Biological Process (3): actin cytoskeleton organization (GO:0030036), regulation of actin filament polymerization (GO:0030833), positive regulation of actin filament bundle assembly (GO:0032233)

GO Molecular Function (2): actin binding (GO:0003779), lipid binding (GO:0008289)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoskeleton organization	1
actin filament-based process	1
regulation of actin polymerization or depolymerization	1
actin filament polymerization	1
regulation of protein polymerization	1
regulation of actin filament bundle assembly	1
positive regulation of cellular component biogenesis	1
actin filament bundle assembly	1
positive regulation of cytoskeleton organization	1
positive regulation of supramolecular fiber organization	1
cytoskeletal protein binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1781 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PFN3	VASP	P50552	998
PFN3	ACTB	P02570	988
PFN3	WAS	P42768	980
PFN3	GSN	P06396	955
PFN3	XPO6	Q96QU8	952
PFN3	APBB1IP	Q7Z5R6	951
PFN3	CFL2	Q9Y281	948
PFN3	CFL1	P23528	948
PFN3	TMSB4X	P01253	934
PFN3	WASL	O00401	899
PFN3	FMNL1	O95466	887
PFN3	SCIN	Q9Y6U3	879
PFN3	ACTR2	P61160	867
PFN3	ACTG1	P02571	862
PFN3	RAPH1	Q70E73	849

IntAct

4 interactions, top by confidence:

A	B	Type	Score
PFN3	ACTB	psi-mi:“MI:0914”(association)	0.350
TCHHL1	PFN3	psi-mi:“MI:0914”(association)	0.350
PFN3	POTEJ	psi-mi:“MI:0914”(association)	0.350

BioGRID (9): ACTC1 (Affinity Capture-MS), ACTB (Affinity Capture-MS), PFN3 (Affinity Capture-MS), ACTBL2 (Affinity Capture-MS), ACTA2 (Affinity Capture-MS), TUBA3C (Affinity Capture-MS), CBWD1 (Affinity Capture-MS), POTEJ (Affinity Capture-MS), TUBA1A (Affinity Capture-MS)

ESM2 similar proteins: A4KA36, A4KA41, A4KA54, A4KA55, A4KA57, A4KA61, A7S6M8, A9UMU8, M0RCP6, P02584, P07274, P07737, P0C0Y3, P25843, P35080, P39825, P49842, P52184, P53696, P60673, P62962, P62963, Q09430, Q0P3X8, Q0VGL1, Q2M2U3, Q2NKT1, Q32PB1, Q42418, Q4R4P8, Q5IRJ7, Q5R483, Q5R4E2, Q64LH2, Q68HB4, Q6QEJ7, Q6VH22, Q8CF66, Q8GT39, Q8NHR9

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.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	26
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
979537	GRCh37/hg19 5q35.2-35.3(chr5:175394616-177436413)x3	Pathogenic
1807722	GRCh37/hg19 5q35.2-35.3(chr5:176547912-177126647)x3	Likely pathogenic

SpliceAI

112 predictions. Top by Δscore:

Variant	Effect	Δscore
5:177400490:G:C	donor_gain	0.9700
5:177400437:T:TA	donor_gain	0.9400
5:177400486:CGCAG:C	donor_gain	0.8600
5:177400521:T:TA	donor_gain	0.8000
5:177400434:ACCT:A	donor_gain	0.7800
5:177400435:CCTC:C	donor_gain	0.7800
5:177400430:GCCCA:G	donor_loss	0.7300
5:177400431:CCCAC:C	donor_loss	0.7300
5:177400432:CCACC:C	donor_loss	0.7300
5:177400433:CA:C	donor_loss	0.7300
5:177400434:A:AG	donor_loss	0.7300
5:177400435:C:A	donor_loss	0.7300
5:177400489:AG:A	donor_gain	0.7300
5:177400436:C:G	donor_loss	0.6800
5:177400386:AGGC:A	donor_gain	0.6700
5:177400489:A:AC	donor_gain	0.6700
5:177400386:AGG:A	donor_gain	0.6600
5:177400481:C:T	donor_gain	0.6600
5:177400564:T:A	donor_gain	0.6600
5:177400392:G:A	donor_gain	0.6500
5:177400497:T:TA	donor_gain	0.6300
5:177400408:G:A	donor_gain	0.6100
5:177400485:A:C	donor_gain	0.5900
5:177400438:C:A	donor_gain	0.5800
5:177400324:CGCCG:C	donor_gain	0.5700
5:177400431:C:CA	donor_gain	0.5600
5:177400484:CACG:C	donor_gain	0.5500
5:177400326:CCG:C	donor_gain	0.5300
5:177400557:TAG:T	donor_gain	0.5300
5:177400558:AGA:A	donor_gain	0.5300

AlphaMissense

870 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:177400449:A:T	I43N	0.953
5:177400512:A:T	I22N	0.949
5:177400515:G:T	A21D	0.947
5:177400350:T:A	D76V	0.946
5:177400377:C:T	G67E	0.936
5:177400567:A:G	W4R	0.936
5:177400567:A:T	W4R	0.936
5:177400449:A:G	I43T	0.935
5:177400481:C:A	W32C	0.933
5:177400481:C:G	W32C	0.933
5:177400215:A:T	L121H	0.929
5:177400351:C:G	D76H	0.929
5:177400350:T:G	D76A	0.928
5:177400449:A:C	I43S	0.926
5:177400359:A:T	V73D	0.925
5:177400522:C:G	D19H	0.923
5:177400212:T:A	N122I	0.922
5:177400520:G:C	D19E	0.917
5:177400520:G:T	D19E	0.917
5:177400516:C:G	A21P	0.916
5:177400349:G:C	D76E	0.913
5:177400349:G:T	D76E	0.913
5:177400425:A:T	L51H	0.912
5:177400354:G:T	R75S	0.910
5:177400243:C:G	G112R	0.908
5:177400521:T:A	D19V	0.907
5:177400356:A:G	I74T	0.906
5:177400483:A:G	W32R	0.904
5:177400483:A:T	W32R	0.904
5:177400280:G:C	C99W	0.902

dbSNP variants (sampled 300 via entrez): RS1000253382 (5:177402599 G>A), RS1001326017 (5:177401256 G>T), RS1001479722 (5:177401482 T>C), RS1002201363 (5:177401109 A>T), RS1002229639 (5:177399729 G>A), RS1002732466 (5:177399983 T>C,G), RS1003208101 (5:177399881 G>A), RS1006054767 (5:177400072 TC>T,TCC), RS1006587732 (5:177400345 G>A,C,T), RS1007642333 (5:177400716 G>A,T), RS1008975357 (5:177402198 G>A,T), RS1009927611 (5:177400948 A>T), RS1010403616 (5:177402511 C>G,T), RS1011078817 (5:177399853 A>G,T), RS1011827952 (5:177401039 G>A)

Disease associations

OMIM: gene MIM:612812 | 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
GCST000649_23	Chronic kidney disease	1.000000e-14
GCST001432_1	Nephrolithiasis	9.000000e-12
GCST001639_21	Metabolite levels	3.000000e-14
GCST005956_15	Waist-to-hip ratio adjusted for BMI	1.000000e-07
GCST005957_13	Waist-to-hip ratio adjusted for BMI (age <50)	3.000000e-07
GCST005962_42	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	1.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004723	coronary artery calcification
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression	1
Benzo(a)pyrene	affects methylation	1
Ivermectin	decreases expression	1
Silicon Dioxide	decreases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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