PHACTR3

Summary

PHACTR3 (phosphatase and actin regulator 3, HGNC:15833) is a protein-coding gene on chromosome 20q13.32-q13.33, encoding Phosphatase and actin regulator 3 (Q96KR7).

This gene encodes a member of the phosphatase and actin regulator protein family. The encoded protein is associated with the nuclear scaffold in proliferating cells, and binds to actin and the catalytic subunit of protein phosphatase-1, suggesting that it functions as a regulatory subunit of protein phosphatase-1. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 116154 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 86 total
• MANE Select transcript: NM_080672

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15833
Approved symbol	PHACTR3
Name	phosphatase and actin regulator 3
Location	20q13.32-q13.33
Locus type	gene with protein product
Status	Approved
Aliases	PPP1R123
Ensembl gene	ENSG00000087495
Ensembl biotype	protein_coding
OMIM	608725
Entrez	116154

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 11 protein_coding, 1 retained_intron

ENST00000355648, ENST00000359926, ENST00000361300, ENST00000371015, ENST00000395636, ENST00000434923, ENST00000473657, ENST00000492611, ENST00000541461, ENST00000908180, ENST00000908181, ENST00000944653

RefSeq mRNA: 6 — MANE Select: NM_080672 NM_001199505, NM_001199506, NM_001281507, NM_080672, NM_183244, NM_183246

CCDS: CCDS13480, CCDS13481, CCDS42895, CCDS56202

Canonical transcript exons

ENST00000371015 — 13 exons

Exon	Start	End
ENSE00000557160	59836505	59836560
ENSE00000845882	59747758	59747835
ENSE00000845883	59755182	59755364
ENSE00000845884	59767186	59767395
ENSE00000845885	59773279	59773453
ENSE00000845886	59774243	59774490
ENSE00000845887	59806041	59806194
ENSE00003485943	59840369	59840430
ENSE00003515025	59743107	59743268
ENSE00003556427	59845189	59845265
ENSE00003593564	59604540	59605132
ENSE00003622454	59847115	59847711
ENSE00003646397	59841395	59841535

Expression profiles

Bgee: expression breadth ubiquitous, 194 present calls, max score 97.14.

FANTOM5 (CAGE): breadth broad, TPM avg 10.6317 / max 1356.8538, expressed in 342 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
185630	4.2784	146
185629	2.3540	144
185631	1.3099	108
185644	1.2137	220
185627	0.8073	142
185636	0.2039	14
185643	0.1235	69
185632	0.1175	50
185634	0.0988	54
185642	0.0664	28

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	97.14	gold quality
amygdala	UBERON:0001876	96.76	gold quality
medial globus pallidus	UBERON:0002477	96.32	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.94	gold quality
globus pallidus	UBERON:0001875	95.91	gold quality
substantia nigra	UBERON:0002038	95.79	gold quality
corpus callosum	UBERON:0002336	95.75	gold quality
anterior cingulate cortex	UBERON:0009835	95.60	gold quality
right frontal lobe	UBERON:0002810	95.56	gold quality
spinal cord	UBERON:0002240	95.50	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.27	gold quality
midbrain	UBERON:0001891	95.12	gold quality
Ammon’s horn	UBERON:0001954	95.12	gold quality
putamen	UBERON:0001874	94.91	gold quality
ganglionic eminence	UBERON:0004023	94.91	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.73	gold quality
prefrontal cortex	UBERON:0000451	94.54	gold quality
hypothalamus	UBERON:0001898	94.54	gold quality
temporal lobe	UBERON:0001871	94.47	gold quality
caudate nucleus	UBERON:0001873	94.31	gold quality
neocortex	UBERON:0001950	94.29	gold quality
frontal cortex	UBERON:0001870	94.28	gold quality
cerebral cortex	UBERON:0000956	94.24	gold quality
nucleus accumbens	UBERON:0001882	93.72	gold quality
lateral globus pallidus	UBERON:0002476	93.71	gold quality
forebrain	UBERON:0001890	93.66	gold quality
brain	UBERON:0000955	93.56	gold quality
substantia nigra pars reticulata	UBERON:0001966	93.37	gold quality
subthalamic nucleus	UBERON:0001906	93.12	gold quality
cerebellar cortex	UBERON:0002129	92.73	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.58

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

45 targeting PHACTR3, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-4528	99.18	69.77	1936
HSA-MIR-3160-3P	99.07	64.78	955

Literature-anchored findings (GeneRIF, showing 6)

• scapinin is a putative regulatory subunit of PP1 and is involved in transformed or immature phenotypes of HL-60 cells (PMID:12925532)
• a highly conserved complex genomic organization with four different leader exons; Alternative splicing of exon 5 was found to be limited to human vs. mouse; expression seems to occur predominantly in the brain (PMID:16974080)
• scapinin enhances cell spreading and motility through direct interaction with actin and PP1 plays a regulatory role in scapinin-induced morphological changes (PMID:19158953)
• E2F4, PHACTR3, PRAME family member and CDH12 most probably play important role in non-small-cell lung cancer geneses (PMID:19473719)
• Because its expression is highest in relatively plastic regions of the adult brain (cortex, hippocampus), scapinin is a new regulator of neurite outgrowth and neuroplasticity in the brain. (PMID:21487013)
• DNA methylation of phosphatase and actin regulator 3 is associated with colorectal cancer. (PMID:22135045)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	phactr3b	ENSDARG00000019304
danio_rerio	phactr3a	ENSDARG00000058243
mus_musculus	Phactr3	ENSMUSG00000027525
rattus_norvegicus	Phactr3	ENSRNOG00000057996
drosophila_melanogaster	CG32264	FBGN0052264
caenorhabditis_elegans	phac-1	WBGENE00009174

Paralogs (3): PHACTR1 (ENSG00000112137), PHACTR2 (ENSG00000112419), PHACTR4 (ENSG00000204138)

Protein

Protein identifiers

Phosphatase and actin regulator 3 — Q96KR7 (reviewed: Q96KR7)

Alternative names: Scaffold-associated PP1-inhibiting protein

All UniProt accessions (3): Q96KR7, A0A5F9ZHM5, F6RP66

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Binds actin and PPP1CA; thus inhibiting the protein phosphatase 1 (PP1) activity.

Subcellular location. Nucleus matrix.

Tissue specificity. Abundantly expressed in brain. Also found in several tumors such as lung carcinomas, nervous tumors and HL-60 leukemia cells. Isoform 3 is the major form in U-937, GOTO and HL-60 leukemia cells.

Induction. Down-regulated in HL-60 leukemia cells by RA, PMA and dimethyl sulfoxide.

Similarity. Belongs to the phosphatase and actin regulator family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q96KR7-1	1, Scapinin 1B	yes
Q96KR7-2	2, Scapinin-L, Scapinin 1C
Q96KR7-3	3, Scapinin-S
Q96KR7-4	4

RefSeq proteins (6): NP_001186434, NP_001186435, NP_001268436, NP_542403, NP_899067, NP_899069 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004018	RPEL_repeat	Repeat

Pfam: PF02755

UniProt features (29 total): compositionally biased region 8, repeat 4, sequence conflict 4, modified residue 3, splice variant 3, region of interest 3, coiled-coil region 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96KR7-F1	64.19	0.24

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 (3): 70, 230, 236

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 166 (showing top): ATF_B, GCANCTGNY_MYOD_Q6, AREB6_03, TGACCTY_ERR1_Q2, TAL1ALPHAE47_01, AP2_Q3, FOXO1_01, GGGTGGRR_PAX4_03, CREB_Q4, AGGAGTG_MIR483, ATF3_Q6, MYOD_Q6, ATF4_Q2, AACTTT_UNKNOWN, GFI1_01

GO Biological Process (1): actin cytoskeleton organization (GO:0030036)

GO Molecular Function (3): actin binding (GO:0003779), protein phosphatase inhibitor activity (GO:0004864), protein binding (GO:0005515)

GO Cellular Component (3): nucleoplasm (GO:0005654), nuclear matrix (GO:0016363), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear lumen	2
cellular anatomical structure	2
cytoskeleton organization	1
actin filament-based process	1
cytoskeletal protein binding	1
phosphoprotein phosphatase activity	1
phosphatase inhibitor activity	1
protein phosphatase regulator activity	1
binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

768 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PHACTR3	TAFA4	Q96LR4	730
PHACTR3	PPP1CA	P08129	717
PHACTR3	TMA16	Q96EY4	529
PHACTR3	PRDM14	Q9GZV8	511
PHACTR3	SMIM17	P0DL12	470
PHACTR3	PHYHIPL	Q96FC7	466
PHACTR3	HS3ST2	Q9Y278	445
PHACTR3	FAM209B	Q5JX69	438
PHACTR3	SIDT2	Q8NBJ9	436
PHACTR3	PEPD	P12955	427
PHACTR3	DPYSL4	O14531	420
PHACTR3	BCAS4	Q8TDM0	405
PHACTR3	PFDN4	Q9NQP4	405
PHACTR3	DUT	P33316	389
PHACTR3	ARRDC2	Q8TBH0	388
PHACTR3	TMEM214	Q6NUQ4	388

IntAct

26 interactions, top by confidence:

A	B	Type	Score
PPP1CB	PHACTR3	psi-mi:“MI:0915”(physical association)	0.560
PHACTR3	CAPNS2	psi-mi:“MI:0915”(physical association)	0.560
CYB5B	PHACTR3	psi-mi:“MI:0915”(physical association)	0.560
PLPP6	PHACTR3	psi-mi:“MI:0915”(physical association)	0.560
PHACTR3	UBL5	psi-mi:“MI:0915”(physical association)	0.560
PHACTR3	UBIAD1	psi-mi:“MI:0915”(physical association)	0.560
PHACTR3	PPP1CA	psi-mi:“MI:0915”(physical association)	0.550
PHACTR3	AMH	psi-mi:“MI:0915”(physical association)	0.400
PHACTR3	TAB1	psi-mi:“MI:0915”(physical association)	0.370
PHACTR3	MAPK6	psi-mi:“MI:0915”(physical association)	0.370
PHACTR3	KCNK3	psi-mi:“MI:0914”(association)	0.350
LXN	PHACTR3	psi-mi:“MI:0915”(physical association)	0.000
PHACTR3	PPP1CB	psi-mi:“MI:0915”(physical association)	0.000
CYB5B	PHACTR3	psi-mi:“MI:0915”(physical association)	0.000
PLPP6	PHACTR3	psi-mi:“MI:0915”(physical association)	0.000
UBL5	PHACTR3	psi-mi:“MI:0915”(physical association)	0.000
CAPNS2	PHACTR3	psi-mi:“MI:0915”(physical association)	0.000
UBIAD1	PHACTR3	psi-mi:“MI:0915”(physical association)	0.000
PHACTR3		psi-mi:“MI:0915”(physical association)	0.000

BioGRID (41): PHACTR3 (Affinity Capture-MS), KCNK3 (Affinity Capture-MS), AMH (Affinity Capture-MS), PPP1CC (Affinity Capture-MS), EIF3B (Affinity Capture-MS), ACTB (Affinity Capture-MS), PPP1CA (Affinity Capture-MS), ACTC1 (Affinity Capture-MS), GTF2I (Affinity Capture-MS), EIF3A (Affinity Capture-MS), LSM14A (Affinity Capture-MS), CPVL (Affinity Capture-MS), ATP10B (Affinity Capture-MS), LRPPRC (Affinity Capture-MS), G3BP1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8ER70, A1L253, A2AHC3, A5WUN7, B1AZP2, D4AEC2, O14490, P28290, P62024, P97836, P97839, Q148W8, Q14CH0, Q2KI52, Q2M3X8, Q3ZBW7, Q4KM62, Q4R2Y2, Q4R707, Q52KF3, Q5PQL8, Q5R3Z9, Q5RD34, Q5RJX2, Q5VUB5, Q5VZP5, Q5XII9, Q6GLU8, Q6NSV7, Q6P995, Q6PEI3, Q6RFY2, Q7T3E8, Q8BJ42, Q8BYK5, Q8C1B1, Q922B9, Q95X94, Q96BN6, Q96KR7

Diamond homologs: F1MCY2, F1N8V3, F1QIC4, F7EC58, O75167, P62024, P62025, Q2M3X8, Q501J7, Q5HZA1, Q5RAU1, Q5XHF3, Q6GLU8, Q6PEI3, Q6RFY2, Q801X6, Q8BYK5, Q8IZ21, Q96KR7, Q9C0D0

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CDK5	“down-regulates quantity”	PHACTR3	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	73
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3420 predictions. Top by Δscore:

Variant	Effect	Δscore
20:59605132:GGTA:G	donor_loss	1.0000
20:59605134:T:A	donor_loss	1.0000
20:59747756:A:AG	acceptor_gain	1.0000
20:59747757:G:GC	acceptor_gain	1.0000
20:59747757:GC:G	acceptor_gain	1.0000
20:59747831:GCAGG:G	donor_gain	1.0000
20:59747834:GG:G	donor_gain	1.0000
20:59747835:GG:G	donor_gain	1.0000
20:59755176:TTGTA:T	acceptor_loss	1.0000
20:59755180:A:AC	acceptor_loss	1.0000
20:59755181:G:GT	acceptor_loss	1.0000
20:59774241:A:AG	acceptor_gain	1.0000
20:59774242:G:GA	acceptor_gain	1.0000
20:59774497:A:T	donor_gain	1.0000
20:59806020:T:TA	acceptor_gain	1.0000
20:59806025:T:TA	acceptor_gain	1.0000
20:59806026:G:A	acceptor_gain	1.0000
20:59806030:G:A	acceptor_gain	1.0000
20:59806036:TTTA:T	acceptor_loss	1.0000
20:59806037:TTAG:T	acceptor_loss	1.0000
20:59806038:TAG:T	acceptor_loss	1.0000
20:59806039:A:AG	acceptor_gain	1.0000
20:59806039:AG:A	acceptor_gain	1.0000
20:59806040:G:GG	acceptor_gain	1.0000
20:59806040:GG:G	acceptor_gain	1.0000
20:59806040:GGA:G	acceptor_gain	1.0000
20:59806040:GGAA:G	acceptor_gain	1.0000
20:59806040:GGAAC:G	acceptor_gain	1.0000
20:59806191:CCAAG:C	donor_loss	1.0000
20:59806192:CAAGT:C	donor_loss	1.0000

AlphaMissense

3641 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:59836520:A:C	R448S	1.000
20:59836520:A:T	R448S	1.000
20:59836537:T:A	L454Q	1.000
20:59836537:T:C	L454P	1.000
20:59836546:G:C	R457T	1.000
20:59836552:T:A	I459N	1.000
20:59836552:T:C	I459T	1.000
20:59836552:T:G	I459S	1.000
20:59836555:T:C	L460S	1.000
20:59840420:T:C	L479S	1.000
20:59840430:G:C	K482N	1.000
20:59840430:G:T	K482N	1.000
20:59841396:T:A	L483H	1.000
20:59841396:T:C	L483P	1.000
20:59841404:A:G	R486G	1.000
20:59841405:G:C	R486T	1.000
20:59841406:A:C	R486S	1.000
20:59841406:A:T	R486S	1.000
20:59841407:C:A	P487T	1.000
20:59841407:C:T	P487S	1.000
20:59841408:C:A	P487H	1.000
20:59841414:T:A	V489D	1.000
20:59841423:T:C	L492S	1.000
20:59841424:A:C	L492F	1.000
20:59841424:A:T	L492F	1.000
20:59841438:T:A	I497N	1.000
20:59841438:T:C	I497T	1.000
20:59841438:T:G	I497S	1.000
20:59841441:T:A	L498Q	1.000
20:59841441:T:C	L498P	1.000

dbSNP variants (sampled 300 via entrez): RS1000000282 (20:59707992 T>C), RS1000036420 (20:59592035 A>G), RS1000055493 (20:59744667 A>G), RS1000070291 (20:59765256 G>A), RS1000086368 (20:59839010 T>G), RS1000087929 (20:59635616 T>C), RS1000088954 (20:59582398 G>A), RS1000098325 (20:59780349 G>A), RS1000100373 (20:59713777 T>C), RS1000107287 (20:59835854 TG>T), RS1000124347 (20:59821179 T>C), RS1000124798 (20:59732940 C>G,T), RS1000133835 (20:59799149 C>G,T), RS1000142673 (20:59632300 G>A), RS1000152198 (20:59702142 G>C)

Disease associations

OMIM: gene MIM:608725 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST005316_253	Intelligence (MTAG)	3.000000e-08
GCST005316_254	Intelligence (MTAG)	8.000000e-10
GCST005316_255	Intelligence (MTAG)	2.000000e-09
GCST005316_256	Intelligence (MTAG)	1.000000e-09
GCST006269_1194	General cognitive ability	4.000000e-08
GCST007201_266	Schizophrenia	3.000000e-06
GCST007201_458	Schizophrenia	8.000000e-06
GCST007843_29	Rheumatoid arthritis	7.000000e-09
GCST009144_18	Disease progression in age-related macular degeneration (adjusted for baseline)	3.000000e-06
GCST010002_70	Refractive error	2.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0008336	disease progression measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases methylation, affects cotreatment, increases expression, affects expression	5
Cadmium Chloride	decreases expression, increases abundance, increases expression	3
Particulate Matter	decreases expression, increases abundance, affects cotreatment, increases expression	3
Tobacco Smoke Pollution	decreases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
aristolochic acid I	increases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
trichostatin A	increases expression	1
sodium arsenite	affects methylation	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects cotreatment, decreases expression, affects response to substance	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
avobenzone	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
NSC 689534	affects binding, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Leflunomide	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Ethanol	affects cotreatment, decreases expression, increases abundance	1
Atrazine	decreases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	1
Cadmium	decreases expression, increases abundance	1
Copper	affects binding, decreases expression	1
Diazinon	decreases methylation	1
Estradiol	increases expression, affects cotreatment	1
Formaldehyde	decreases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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