PFN4

Summary

PFN4 (profilin family member 4, HGNC:31103) is a protein-coding gene on chromosome 2p23.3, encoding Profilin-4 (Q8NHR9). Involved in male fertility.

Predicted to enable actin monomer binding activity. Predicted to be involved in acrosome assembly; manchette assembly; and sperm flagellum assembly. Predicted to be located in cytoplasm. Predicted to be active in cell cortex.

Source: NCBI Gene 375189 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_199346

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31103
Approved symbol	PFN4
Name	profilin family member 4
Location	2p23.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000176732
Ensembl biotype	protein_coding
OMIM	620046
Entrez	375189

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000313213, ENST00000436622, ENST00000465360, ENST00000897652, ENST00000897653, ENST00000897654, ENST00000897655, ENST00000897656, ENST00000897657, ENST00000897658

RefSeq mRNA: 1 — MANE Select: NM_199346 NM_199346

CCDS: CCDS1709

Canonical transcript exons

ENST00000313213 — 5 exons

Exon	Start	End
ENSE00001270730	24123118	24123334
ENSE00001270738	24114809	24115611
ENSE00001270748	24122419	24122547
ENSE00003512583	24119577	24119682
ENSE00003637815	24121163	24121300

Expression profiles

Bgee: expression breadth ubiquitous, 161 present calls, max score 97.17.

FANTOM5 (CAGE): breadth broad, TPM avg 1.0045 / max 272.9064, expressed in 440 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
27316	0.4745	214
27318	0.2548	45
27319	0.1847	46
27317	0.0906	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	97.17	gold quality
right testis	UBERON:0004534	96.71	gold quality
testis	UBERON:0000473	94.78	gold quality
sperm	CL:0000019	93.26	gold quality
adult organism	UBERON:0007023	90.94	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.24	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.39	gold quality
pancreatic ductal cell	CL:0002079	80.70	silver quality
oviduct epithelium	UBERON:0004804	72.98	gold quality
left ovary	UBERON:0002119	71.19	gold quality
tibial nerve	UBERON:0001323	70.47	gold quality
lower esophagus mucosa	UBERON:0035834	69.90	gold quality
right ovary	UBERON:0002118	69.83	gold quality
tibialis anterior	UBERON:0001385	69.77	silver quality
buccal mucosa cell	CL:0002336	69.55	silver quality
right uterine tube	UBERON:0001302	69.08	gold quality
adenohypophysis	UBERON:0002196	68.63	gold quality
popliteal artery	UBERON:0002250	68.57	gold quality
tibial artery	UBERON:0007610	68.57	gold quality
metanephros cortex	UBERON:0010533	68.07	gold quality
calcaneal tendon	UBERON:0003701	67.74	gold quality
cortical plate	UBERON:0005343	67.15	gold quality
ventricular zone	UBERON:0003053	66.97	gold quality
pituitary gland	UBERON:0000007	66.93	gold quality
ovary	UBERON:0000992	66.90	gold quality
ileal mucosa	UBERON:0000331	66.85	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	66.82	gold quality
endocervix	UBERON:0000458	66.64	gold quality
right lobe of thyroid gland	UBERON:0001119	66.47	gold quality
aorta	UBERON:0000947	66.46	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	27.74
E-ANND-3	no	3.36

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

48 targeting PFN4, 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-5692A	100.00	74.40	6850
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-324-3P	99.26	66.31	1034
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-143-5P	98.98	68.87	946
HSA-MIR-511-5P	98.97	70.94	2268
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-219A-1-3P	98.91	67.87	639
HSA-MIR-6871-5P	98.90	66.67	671
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-6830-3P	98.62	68.07	1760
HSA-MIR-1261	98.62	68.10	896

Literature-anchored findings (GeneRIF, showing 1)

• Porfilin 4 bound to selected phosphoinositides but not to poly-L-proline, proline-rich proteins, or actin. (PMID:19419568)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pfn4	ENSDARG00000097487
mus_musculus	Pfn4	ENSMUSG00000020639
rattus_norvegicus	Pfn4	ENSRNOG00000050386
drosophila_melanogaster	chic	FBGN0000308
caenorhabditis_elegans		WBGENE00003991

Protein

Protein identifiers

Profilin-4 — Q8NHR9 (reviewed: Q8NHR9)

Alternative names: Profilin IV

All UniProt accessions (2): Q8NHR9, A0A1D5RMN8

UniProt curated annotations — full annotation on UniProt →

Function. Involved in male fertility. Required for manchette development and acrosome biogenesis during spermiogenesis. Binds in vitro to phospholipids, including phosphatidylinositol 3-phosphate (PtdIns(3)P), phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), phosphatidylinositol 4-phosphate (PtdIns(4)P) and phosphatidic acid (PA). Contrary to other profilin family members, does not bind to actin in vitro.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed in testis, in germ cells in seminiferous tubules (at protein level). Prominently expressed in pachytene/diplotene stage spematocytes.

Similarity. Belongs to the profilin family.

RefSeq proteins (1): NP_955378* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
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-Q8NHR9-F1	94.16	0.84

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 62 (showing top): GOBP_VESICLE_ORGANIZATION, GOBP_MALE_GAMETE_GENERATION, GOBP_SECRETORY_GRANULE_ORGANIZATION, GOBP_CELLULAR_COMPONENT_ASSEMBLY_INVOLVED_IN_MORPHOGENESIS, GOBP_CILIUM_ORGANIZATION, GOBP_CILIUM_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_ACROSOME_ASSEMBLY, GOBP_ORGANELLE_ASSEMBLY, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOMF_ACTIN_BINDING, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_MOTILE_CILIUM_ASSEMBLY, GOBP_CELL_PROJECTION_ORGANIZATION

GO Biological Process (6): acrosome assembly (GO:0001675), spermatogenesis (GO:0007283), flagellated sperm motility (GO:0030317), sperm flagellum assembly (GO:0120316), manchette assembly (GO:1905198), cell differentiation (GO:0030154)

GO Molecular Function (3): actin monomer binding (GO:0003785), lipid binding (GO:0008289), actin binding (GO:0003779)

GO Cellular Component (2): cell cortex (GO:0005938), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
developmental process involved in reproduction	3
spermatid development	3
cellular component assembly involved in morphogenesis	1
cellular process involved in reproduction in multicellular organism	1
secretory granule organization	1
organelle assembly	1
male gamete generation	1
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
flagellated sperm motility	1
motile cilium assembly	1
cellular component assembly	1
cellular developmental process	1
actin binding	1
binding	1
cytoskeletal protein binding	1
cytoplasm	1
cell periphery	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2018 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PFN4	VASP	P50552	998
PFN4	ACTB	P02570	989
PFN4	WAS	P42768	984
PFN4	GSN	P06396	960
PFN4	CFL2	Q9Y281	958
PFN4	CFL1	P23528	957
PFN4	XPO6	Q96QU8	954
PFN4	APBB1IP	Q7Z5R6	951
PFN4	TMSB4X	P01253	934
PFN4	WASL	O00401	919
PFN4	SCIN	Q9Y6U3	892
PFN4	FMNL1	O95466	892
PFN4	ACTR2	P61160	886
PFN4	ACTG1	P02571	872
PFN4	RAPH1	Q70E73	850

IntAct

3 interactions, top by confidence:

A	B	Type	Score
INSR	BLTP3B	psi-mi:“MI:0914”(association)	0.350

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: A4GCR7, A4GD56, A4GDR8, A4GDT0, A4GE44, A4GFB7, A4GFB9, A4GFC2, A4GFC4, A4K9Z8, A4KA38, A4KA39, A4KA40, A4KA41, A4KA44, A4KA45, A4KA55, C6JWH0, O04725, O65812, P07274, P18322, P19984, P22271, P25816, P25843, P26199, P26200, P35081, P35083, P39825, P49230, P53696, P68696, P84177, Q21193, Q2NKT1, Q38905, Q42449, Q5IRJ7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1087 predictions. Top by Δscore:

Variant	Effect	Δscore
2:24119575:A:AC	donor_gain	1.0000
2:24119575:AC:A	donor_gain	1.0000
2:24119576:C:CC	donor_gain	1.0000
2:24119576:CC:C	donor_gain	1.0000
2:24119680:CTC:C	acceptor_gain	1.0000
2:24119683:C:CC	acceptor_gain	1.0000
2:24121161:A:AC	donor_gain	1.0000
2:24121162:C:CC	donor_gain	1.0000
2:24122417:A:AC	donor_gain	1.0000
2:24122418:C:CC	donor_gain	1.0000
2:24123213:C:A	donor_gain	1.0000
2:24123636:G:GT	donor_gain	1.0000
2:24115609:CTCCT:C	acceptor_loss	0.9900
2:24115612:CTGAA:C	acceptor_loss	0.9900
2:24115613:T:C	acceptor_loss	0.9900
2:24118676:G:C	acceptor_gain	0.9900
2:24119570:AACTT:A	donor_loss	0.9900
2:24119571:ACTT:A	donor_loss	0.9900
2:24119572:CT:C	donor_loss	0.9900
2:24119573:TT:T	donor_loss	0.9900
2:24119574:TA:T	donor_loss	0.9900
2:24119575:A:AA	donor_loss	0.9900
2:24119576:C:CT	donor_loss	0.9900
2:24119678:TTCTC:T	acceptor_gain	0.9900
2:24119679:TCTC:T	acceptor_gain	0.9900
2:24119679:TCTCC:T	acceptor_loss	0.9900
2:24119680:CTCC:C	acceptor_gain	0.9900
2:24119681:TC:T	acceptor_gain	0.9900
2:24119681:TCCT:T	acceptor_gain	0.9900
2:24119682:CC:C	acceptor_gain	0.9900

AlphaMissense

824 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:24119599:A:C	C113W	0.984
2:24119633:G:T	A102E	0.979
2:24122472:C:G	A22P	0.976
2:24121170:G:T	A83D	0.975
2:24121194:C:G	R75P	0.975
2:24119601:A:G	C113R	0.974
2:24122471:G:T	A22D	0.972
2:24122474:G:T	A21E	0.971
2:24119600:C:T	C113Y	0.970
2:24121171:C:G	A83P	0.967
2:24121192:C:G	A76P	0.967
2:24119592:C:G	A116P	0.966
2:24121176:A:G	L81P	0.965
2:24122483:A:T	V18E	0.965
2:24119663:A:T	V92D	0.962
2:24119634:C:G	A102P	0.961
2:24119666:A:T	V91D	0.960
2:24119642:A:G	L99P	0.958
2:24119672:C:T	G89D	0.957
2:24122468:A:G	L23P	0.956
2:24121201:A:G	C73R	0.955
2:24122475:C:G	A21P	0.952
2:24121262:A:C	F52L	0.951
2:24121262:A:T	F52L	0.951
2:24121264:A:G	F52L	0.951
2:24115602:A:G	L124P	0.949
2:24121221:A:G	F66S	0.945
2:24119605:G:C	S111R	0.944
2:24119605:G:T	S111R	0.944
2:24119607:T:G	S111R	0.944

dbSNP variants (sampled 300 via entrez): RS1000436993 (2:24120208 G>A), RS1001439737 (2:24118334 G>A), RS1001622513 (2:24118910 A>C,T), RS1002180794 (2:24117839 T>G), RS1002345727 (2:24124603 G>C), RS1002359544 (2:24120481 A>T), RS1002699816 (2:24124952 G>A), RS1002999815 (2:24117340 C>T), RS1003029061 (2:24122009 G>C), RS1003182111 (2:24116461 G>C), RS1003297352 (2:24123602 C>T), RS1003780134 (2:24116686 C>G,T), RS1003794072 (2:24123711 G>A,C,T), RS1003928709 (2:24116724 G>T), RS1004118024 (2:24123638 C>T)

Disease associations

OMIM: gene MIM:620046 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sotorasib	affects cotreatment, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
jinfukang	affects cotreatment, increases expression	1
trametinib	affects cotreatment, increases expression	1
NVP-BKM120	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	increases methylation	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects cotreatment, increases expression	1
Lead	decreases expression	1
Cyclosporine	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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