PPP4R3C

Summary

PPP4R3C (protein phosphatase 4 regulatory subunit 3C, HGNC:33146) is a protein-coding gene on chromosome Xp21.3, encoding Protein PPP4R3C (Q6ZMV5).

Predicted to enable protein phosphatase activator activity. Predicted to be involved in DNA damage response and regulation of double-strand break repair. Predicted to be located in nucleus. Predicted to be part of protein phosphatase 4 complex. Predicted to be active in nucleoplasm.

Source: NCBI Gene 139420 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 3 total
• MANE Select transcript: NM_207319

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33146
Approved symbol	PPP4R3C
Name	protein phosphatase 4 regulatory subunit 3C
Location	Xp21.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ32867, FLFL3P, smk1
Ensembl gene	ENSG00000224960
Ensembl biotype	protein_coding
Entrez	139420

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000412172

RefSeq mRNA: 1 — MANE Select: NM_207319 NM_207319

CCDS: CCDS87732

Canonical transcript exons

ENST00000412172 — 1 exons

Exon	Start	End
ENSE00001711439	27460207	27463341

Expression profiles

Bgee: expression breadth tissue_specific, 10 present calls, max score 80.16.

Top tissues by expression

246 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	80.16	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	64.58	gold quality
lower lobe of lung	UBERON:0008949	55.07	silver quality
right testis	UBERON:0004534	52.44	gold quality
testis	UBERON:0000473	51.39	gold quality
left testis	UBERON:0004533	49.33	gold quality
buccal mucosa cell	CL:0002336	44.21	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
placenta	UBERON:0001987	42.59	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
vastus lateralis	UBERON:0001379	41.41	gold quality
quadriceps femoris	UBERON:0001377	41.37	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
oviduct epithelium	UBERON:0004804	41.11	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
amniotic fluid	UBERON:0000173	40.69	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
biceps brachii	UBERON:0001507	40.57	gold quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality
myocardium	UBERON:0002349	40.45	gold quality
gingival epithelium	UBERON:0001949	40.43	gold quality
germinal epithelium of ovary	UBERON:0001304	40.33	gold quality
esophagus squamous epithelium	UBERON:0006920	40.29	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	40.27	gold quality
jejunum	UBERON:0002115	40.18	gold quality
cartilage tissue	UBERON:0002418	40.06	gold quality
mammary duct	UBERON:0001765	39.98	gold quality
mucosa of sigmoid colon	UBERON:0004993	39.95	gold quality
deltoid	UBERON:0001476	39.83	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.63

Regulation

Is transcription factor: no

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	ppp4r3b	ENSDARG00000103415
mus_musculus	Ppp4r3c1	ENSMUSG00000035387
mus_musculus	Ppp4r3c2	ENSMUSG00000079513
rattus_norvegicus	AABR07038788.1	ENSRNOG00000029559
rattus_norvegicus	Ppp4r3cl2	ENSRNOG00000031719
rattus_norvegicus	Ppp4r3cl3	ENSRNOG00000051287
rattus_norvegicus		ENSRNOG00000089952
drosophila_melanogaster	flfl	FBGN0024555
caenorhabditis_elegans		WBGENE00018285

Paralogs (2): PPP4R3A (ENSG00000100796), PPP4R3B (ENSG00000275052)

Protein

Protein identifiers

Protein PPP4R3C — Q6ZMV5 (reviewed: Q6ZMV5)

Alternative names: SMEK homolog 3, Serine/threonine-protein phosphatase 4 regulatory subunit 3C

All UniProt accessions (1): Q6ZMV5

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the SMEK family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6ZMV5-1	1	yes
Q6ZMV5-2	2

RefSeq proteins (1): NP_997202* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006887	P4R3-like_central_dom	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR051137	PP4R3-like	Family
IPR055236	EVH1_PP4R3	Domain

Pfam: PF04802, PF22972

UniProt features (9 total): compositionally biased region 4, sequence conflict 2, chain 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZMV5-F1	76.16	0.48

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 36 (showing top): GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_REGULATION_OF_DNA_REPAIR, COUP_01, BRN2_01, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_DNA_DAMAGE_RESPONSE, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_STRESS, GOBP_DNA_METABOLIC_PROCESS, GOMF_PHOSPHATASE_ACTIVATOR_ACTIVITY, GOBP_DNA_REPAIR, GOMF_ENZYME_ACTIVATOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, GOMF_PHOSPHATASE_REGULATOR_ACTIVITY, RP58_01, chrXp21

GO Biological Process (2): DNA damage response (GO:0006974), regulation of double-strand break repair (GO:2000779)

GO Molecular Function (2): protein phosphatase activator activity (GO:0072542), protein phosphatase regulator activity (GO:0019888)

GO Cellular Component (3): nucleoplasm (GO:0005654), protein phosphatase 4 complex (GO:0030289), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phosphoprotein phosphatase activity	2
cellular response to stress	1
regulation of DNA repair	1
double-strand break repair	1
phosphatase activator activity	1
protein phosphatase regulator activity	1
phosphatase regulator activity	1
protein phosphatase binding	1
nuclear lumen	1
cellular anatomical structure	1
protein serine/threonine phosphatase complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

534 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPP4R3C	SCGB1D4	Q6XE38	570
PPP4R3C	PPP4R2	Q9NY27	498
PPP4R3C	SENP7	Q9BQF6	480
PPP4R3C	HCFC1	P51610	474
PPP4R3C	PPP4C	P33172	442
PPP4R3C	KRI1	Q8N9T8	436
PPP4R3C	HORMAD2	Q8N7B1	419
PPP4R3C	SPATA31A6	Q5VVP1	417
PPP4R3C	MEAK7	Q6P9B6	395
PPP4R3C	RIMS4	Q9H426	394
PPP4R3C	HORMAD1	Q86X24	390
PPP4R3C	MYRF	Q9Y2G1	370
PPP4R3C	RNF212	Q495C1	353
PPP4R3C	GSC2	O15499	348
PPP4R3C	TCERG1	O14776	342

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A1D5P556, F1LVW7, F1M775, F4JN05, F4JSZ5, J9SQF3, O08808, O60610, O82233, O95466, P0C5K2, P0C5K3, P0C5K4, P0C5K5, P0CG39, P58069, Q0VAA2, Q15111, Q15283, Q3T0T8, Q3USB7, Q3V124, Q4V3E2, Q569R5, Q62688, Q63713, Q6K641, Q6NXC0, Q6R8G2, Q6R8G4, Q6RG78, Q6ZMV5, Q6ZPF4, Q7Z4N2, Q80YW0, Q84WJ0, Q864Z2, Q8CIR4, Q8N140, Q9C7P6

Diamond homologs: Q3V0Y1, Q4S6U8, Q54I18, Q5MIZ7, Q5SP90, Q6DFT3, Q6IN85, Q6INN7, Q6P2K6, Q6ZMV5, Q7ZX60, Q801Q7, Q922R5, Q9VFS5, Q9Y7J8, Q6CQ91, Q75E32

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

5573 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:27463045:G:C	F84L	0.994
X:27463045:G:T	F84L	0.994
X:27463047:A:G	F84L	0.994
X:27462773:A:G	L175P	0.993
X:27463046:A:G	F84S	0.991
X:27462624:A:G	C225R	0.990
X:27462875:A:T	L141H	0.987
X:27463052:A:G	L82P	0.987
X:27463172:A:T	V42D	0.985
X:27461372:A:G	L642S	0.984
X:27462716:A:G	L194S	0.984
X:27463017:A:G	W94R	0.984
X:27463017:A:T	W94R	0.984
X:27463083:A:G	W72R	0.984
X:27463083:A:T	W72R	0.984
X:27463178:A:G	L40P	0.984
X:27462620:A:G	L226P	0.983
X:27461419:A:C	F626L	0.981
X:27461419:A:T	F626L	0.981
X:27461421:A:G	F626L	0.981
X:27462725:A:G	L191S	0.981
X:27462751:A:C	C182W	0.981
X:27463015:C:A	W94C	0.980
X:27463015:C:G	W94C	0.980
X:27463142:A:G	L52P	0.980
X:27462622:G:C	C225W	0.979
X:27462616:C:A	E227D	0.978
X:27462616:C:G	E227D	0.978
X:27462580:C:A	R239S	0.977
X:27462580:C:G	R239S	0.977

dbSNP variants (sampled 300 via entrez): RS1000639024 (X:27464956 T>C), RS1000824814 (X:27464052 C>T), RS1001714154 (X:27463425 A>C,G), RS1002333573 (X:27463654 G>A,T), RS1003125336 (X:27461436 G>A), RS1003574763 (X:27462489 G>C), RS1004212695 (X:27465219 T>C), RS1005602641 (X:27461700 T>C), RS1006206111 (X:27461247 A>C,G), RS1006283309 (X:27460845 T>C), RS1006572594 (X:27463450 G>A), RS1007012779 (X:27463759 C>T), RS1007565129 (X:27460055 C>T), RS1011063546 (X:27460320 C>T), RS1013879553 (X:27464889 A>G)

Disease associations

OMIM: gene `` | 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

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
zinc chromate	increases abundance, increases expression	1
chromium hexavalent ion	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Estradiol	decreases expression	1

Clinical trials (associated diseases)

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