PPM1J

Summary

PPM1J (protein phosphatase, Mg2+/Mn2+ dependent 1J, HGNC:20785) is a protein-coding gene on chromosome 1p13.2, encoding Protein phosphatase 1J (Q5JR12).

This gene encodes the serine/threonine protein phosphatase. The mouse homolog of this gene apparently belongs to the protein phosphatase 2C family of genes. The exact function of this gene is not yet known.

Source: NCBI Gene 333926 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 88 total
• MANE Select transcript: NM_005167

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20785
Approved symbol	PPM1J
Name	protein phosphatase, Mg2+/Mn2+ dependent 1J
Location	1p13.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ35951, MGC19531, DKFZp434P1514, PP2Czeta, PPP2CZ
Ensembl gene	ENSG00000155367
Ensembl biotype	protein_coding
OMIM	609957
Entrez	333926

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000309276, ENST00000464951, ENST00000471106, ENST00000482367, ENST00000486709, ENST00000885786, ENST00000885787, ENST00000959101

RefSeq mRNA: 1 — MANE Select: NM_005167 NM_005167

CCDS: CCDS855

Canonical transcript exons

ENST00000309276 — 10 exons

Exon	Start	End
ENSE00001909279	112709998	112710310
ENSE00001924238	112714976	112715332
ENSE00003469654	112712744	112713031
ENSE00003532042	112713497	112713611
ENSE00003695126	112710744	112710851
ENSE00003695313	112710460	112710611
ENSE00003695840	112711266	112711384
ENSE00003696447	112711008	112711071
ENSE00003697099	112712345	112712457
ENSE00003701483	112711971	112712055

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 93.96.

FANTOM5 (CAGE): breadth broad, TPM avg 1.3668 / max 100.4426, expressed in 645 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
13880	1.0352	580
13878	0.2882	80
13881	0.0316	9
13882	0.0118	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	93.96	gold quality
left testis	UBERON:0004533	93.64	gold quality
testis	UBERON:0000473	92.57	gold quality
quadriceps femoris	UBERON:0001377	90.85	silver quality
hindlimb stylopod muscle	UBERON:0004252	89.73	gold quality
gastrocnemius	UBERON:0001388	86.07	gold quality
muscle of leg	UBERON:0001383	85.97	gold quality
skeletal muscle tissue	UBERON:0001134	85.75	gold quality
apex of heart	UBERON:0002098	84.52	gold quality
right hemisphere of cerebellum	UBERON:0014890	83.07	gold quality
cerebellar vermis	UBERON:0004720	82.32	gold quality
cerebellar cortex	UBERON:0002129	81.80	gold quality
cerebellum	UBERON:0002037	81.78	gold quality
cerebellar hemisphere	UBERON:0002245	81.78	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.57	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.30	gold quality
skin of abdomen	UBERON:0001416	80.28	gold quality
muscle tissue	UBERON:0002385	80.13	gold quality
zone of skin	UBERON:0000014	80.00	gold quality
skin of leg	UBERON:0001511	79.82	gold quality
heart left ventricle	UBERON:0002084	78.07	gold quality
lower esophagus mucosa	UBERON:0035834	77.79	gold quality
thymus	UBERON:0002370	77.31	silver quality
right frontal lobe	UBERON:0002810	77.10	gold quality
prefrontal cortex	UBERON:0000451	76.98	gold quality
frontal cortex	UBERON:0001870	76.86	gold quality
primary visual cortex	UBERON:0002436	76.70	gold quality
right atrium auricular region	UBERON:0006631	76.28	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	75.85	gold quality
amygdala	UBERON:0001876	75.73	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.28

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

28 targeting PPM1J, 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-3064-3P	100.00	70.09	1254
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-12121	99.99	66.64	255
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-3975	99.62	65.97	697
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-4677-3P	99.49	67.91	1246
HSA-MIR-7151-5P	99.37	67.82	613
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-7974	99.24	65.48	1137
HSA-MIR-3154	98.94	66.55	1455
HSA-MIR-4656	98.79	66.22	1306
HSA-MIR-1537-5P	98.70	68.33	999
HSA-MIR-5088-3P	98.29	66.63	1310
HSA-MIR-7850-5P	98.12	67.28	1111
HSA-MIR-4675	97.69	64.82	774
HSA-MIR-4741	97.69	64.14	883
HSA-MIR-192-3P	97.52	67.66	1001
HSA-MIR-3620-5P	97.42	63.95	792
HSA-MIR-6501-5P	97.41	68.24	712
HSA-MIR-1587	96.95	64.03	932
HSA-MIR-5192	96.89	63.35	879

Cross-species orthologs

17 orthologs

Organism	Symbol	Gene ID
danio_rerio	ppm1na	ENSDARG00000010231
danio_rerio	ppm1nb	ENSDARG00000057032
danio_rerio	ppm1h	ENSDARG00000063684
danio_rerio	ppm1j	ENSDARG00000074690
mus_musculus	Ppm1j	ENSMUSG00000002228
rattus_norvegicus	Ppm1j	ENSRNOG00000012481
drosophila_melanogaster	Pdp	FBGN0029958
drosophila_melanogaster	CG17598	FBGN0031194
drosophila_melanogaster	CG10376	FBGN0032702
drosophila_melanogaster	Ppm1	FBGN0035143
drosophila_melanogaster	CG17746	FBGN0035425
drosophila_melanogaster	Nil	FBGN0039421
drosophila_melanogaster	alph	FBGN0086361
caenorhabditis_elegans		WBGENE00006460
caenorhabditis_elegans		WBGENE00016580
caenorhabditis_elegans		WBGENE00018362
caenorhabditis_elegans	pdp-1	WBGENE00022832

Paralogs (16): PPM1F (ENSG00000100034), TAB1 (ENSG00000100324), PPM1A (ENSG00000100614), PPM1H (ENSG00000111110), PPM1G (ENSG00000115241), ILKAP (ENSG00000132323), PPM1B (ENSG00000138032), PPM1L (ENSG00000163590), PPM1K (ENSG00000163644), PPM1M (ENSG00000164088), PDP1 (ENSG00000164951), PPM1D (ENSG00000170836), PDP2 (ENSG00000172840), PPM1E (ENSG00000175175), PP2D1 (ENSG00000183977), PPM1N (ENSG00000213889)

Protein

Protein identifiers

Protein phosphatase 1J — Q5JR12 (reviewed: Q5JR12)

Alternative names: Protein phosphatase 2C isoform zeta

All UniProt accessions (3): Q5JR12, S4R3C3, S4R3I3

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with UBE2I/UBC9.

Similarity. Belongs to the PP2C family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5JR12-1	1	yes
Q5JR12-2	2

RefSeq proteins (1): NP_005158* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001932	PPM-type_phosphatase-like_dom	Domain
IPR015655	PP2C	Family
IPR036457	PPM-type-like_dom_sf	Homologous_superfamily

Pfam: PF00481

Catalyzed reactions (Rhea), 2 shown:

• O-phospho-L-seryl-[protein] + H2O = L-seryl-[protein] + phosphate (RHEA:20629)
• O-phospho-L-threonyl-[protein] + H2O = L-threonyl-[protein] + phosphate (RHEA:47004)

UniProt features (10 total): modified residue 2, splice variant 2, sequence variant 2, chain 1, domain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5JR12-F1	84.86	0.72

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 (2): 66, 76

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 131 (showing top): XU_GH1_AUTOCRINE_TARGETS_UP, LFA1_Q6, GCANCTGNY_MYOD_Q6, AREB6_03, MAZ_Q6, AP4_Q6, CAGCTG_AP4_Q5, ATF1_Q6, AACTTT_UNKNOWN, PID_P53_DOWNSTREAM_PATHWAY, VDR_Q3, E2F_Q6_01, AP4_01, TUOMISTO_TUMOR_SUPPRESSION_BY_COL13A1_DN, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS

GO Biological Process (1): protein dephosphorylation (GO:0006470)

GO Molecular Function (5): [pyruvate dehydrogenase (acetyl-transferring)]-phosphatase activity (GO:0004741), phosphoprotein phosphatase activity (GO:0004721), protein serine/threonine phosphatase activity (GO:0004722), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (1): mitochondrion (GO:0005739)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
dephosphorylation	1
protein modification process	1
protein serine/threonine phosphatase activity	1
phosphatase activity	1
catalytic activity, acting on a protein	1
phosphoprotein phosphatase activity	1
binding	1
catalytic activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

314 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPM1J	UBE2I	P50550	561
PPM1J	SUMO1	P55856	510
PPM1J	PPTC7	Q8NI37	503
PPM1J	PPM1A	P35813	463
PPM1J	PPM1K	Q8N3J5	463
PPM1J	MAPK9	P45984	454
PPM1J	PDP1	Q9P0J1	449
PPM1J	KLHDC7A	Q5VTJ3	432
PPM1J	SLCO6A1	Q86UG4	424
PPM1J	RILPL1	Q5EBL4	422
PPM1J	ILKAP	Q9H0C8	410
PPM1J	EDEM3	Q9BZQ6	397
PPM1J	PP2D1	A8MPX8	390
PPM1J	SLC25A45	Q8N413	379
PPM1J	PPM1D	O15297	376

IntAct

25 interactions, top by confidence:

A	B	Type	Score
PPM1J	LGALS14	psi-mi:“MI:0915”(physical association)	0.560
PPM1J	SMARCD1	psi-mi:“MI:0915”(physical association)	0.560
PLEKHN1	PPM1J	psi-mi:“MI:0915”(physical association)	0.560
PPM1J	SPG21	psi-mi:“MI:0915”(physical association)	0.560
PPM1H	YWHAQ	psi-mi:“MI:0914”(association)	0.530
SS18L2	ARID1A	psi-mi:“MI:0914”(association)	0.480
	RAB10	psi-mi:“MI:0203”(dephosphorylation reaction)	0.440
PPM1J	ADORA2A	psi-mi:“MI:0915”(physical association)	0.370
PPM1J	F2RL1	psi-mi:“MI:0915”(physical association)	0.370
PPM1J	GPR37	psi-mi:“MI:0915”(physical association)	0.370
PPM1J	PTAFR	psi-mi:“MI:0915”(physical association)	0.370
PPM1H	ACACB	psi-mi:“MI:0914”(association)	0.350
PPM1J	ACTR3	psi-mi:“MI:0914”(association)	0.350
TXNDC2	H2AZ1	psi-mi:“MI:0914”(association)	0.350
PPM1J	CDKN2C	psi-mi:“MI:0914”(association)	0.350
PPM1J	TCP1	psi-mi:“MI:2364”(proximity)	0.270
LGALS14	PPM1J	psi-mi:“MI:0915”(physical association)	0.000
PLEKHN1	PPM1J	psi-mi:“MI:0915”(physical association)	0.000
SPG21	PPM1J	psi-mi:“MI:0915”(physical association)	0.000
SMARCD1	PPM1J	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (27): PPM1J (Affinity Capture-MS), ACTR3 (Affinity Capture-MS), BAX (Affinity Capture-MS), DPYSL3 (Affinity Capture-MS), NUFIP2 (Affinity Capture-MS), PPM1H (Affinity Capture-MS), PPM1M (Affinity Capture-MS), SLTM (Affinity Capture-MS), CCT7 (Proximity Label-MS), CCT2 (Proximity Label-MS), CCT5 (Proximity Label-MS), CCT3 (Proximity Label-MS), TCP1 (Proximity Label-MS), CCT4 (Proximity Label-MS), PPM1J (Reconstituted Complex)

ESM2 similar proteins: D4A1F2, E9Q4Z2, F1MF74, F1QWK4, F1RA39, O00763, O81760, O88484, O94851, P51432, P59679, Q01970, Q05AL2, Q09M05, Q0V7V2, Q10S32, Q12851, Q149T7, Q15750, Q28DF4, Q2QN36, Q4U2V3, Q501F9, Q504M2, Q5JR12, Q5MFV5, Q5PNS9, Q5Z8P0, Q641Y6, Q6F6B3, Q6ING9, Q6ZHC8, Q7XCJ7, Q7XJ53, Q7XUC5, Q7Y138, Q7ZU92, Q8BML1, Q8BU27, Q8CF89

Diamond homologs: Q05AL2, Q149T7, Q28DF4, Q2RBJ6, Q3EAF9, Q3EAZ3, Q3UYC0, Q5JR12, Q5M821, Q641Y6, Q8BU27, Q96MI6, Q9P2J9, Q9ULR3, Q53Q11, Q67UX7, Q8LAY8, Q8RXV3, Q9SLA1, P35182, Q9FIF5, Q9LNW3, Q9SUF4, A5PJZ2, O62830, O75688, P35815, P36993, Q5SGD2, Q8BHN0, O62829

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
MAPK10	down-regulates	PPM1J	phosphorylation
MAPK8	down-regulates	PPM1J	phosphorylation
MAPK9	down-regulates	PPM1J	phosphorylation
JNK	down-regulates	PPM1J	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

88 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	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1965 predictions. Top by Δscore:

Variant	Effect	Δscore
1:112710607:CGTAC:C	acceptor_gain	1.0000
1:112710608:GTAC:G	acceptor_gain	1.0000
1:112710609:TAC:T	acceptor_gain	1.0000
1:112710609:TACC:T	acceptor_loss	1.0000
1:112710610:AC:A	acceptor_gain	1.0000
1:112710610:ACC:A	acceptor_loss	1.0000
1:112710611:CC:C	acceptor_gain	1.0000
1:112710611:CCTG:C	acceptor_loss	1.0000
1:112710612:C:CA	acceptor_loss	1.0000
1:112710612:C:CC	acceptor_gain	1.0000
1:112710613:T:A	acceptor_loss	1.0000
1:112710615:G:GC	acceptor_gain	1.0000
1:112710738:GCTCA:G	donor_loss	1.0000
1:112710739:CTCAC:C	donor_loss	1.0000
1:112710740:TCA:T	donor_loss	1.0000
1:112710741:CAC:C	donor_loss	1.0000
1:112710742:ACCTC:A	donor_loss	1.0000
1:112710743:C:CT	donor_loss	1.0000
1:112710847:CGAGC:C	acceptor_gain	1.0000
1:112710848:GAGC:G	acceptor_gain	1.0000
1:112710850:GC:G	acceptor_gain	1.0000
1:112710850:GCCT:G	acceptor_loss	1.0000
1:112710851:CC:C	acceptor_gain	1.0000
1:112710851:CCT:C	acceptor_loss	1.0000
1:112710851:CCTG:C	acceptor_loss	1.0000
1:112710852:C:CA	acceptor_loss	1.0000
1:112710852:C:CC	acceptor_gain	1.0000
1:112710852:CT:C	acceptor_loss	1.0000
1:112710853:T:A	acceptor_loss	1.0000
1:112711180:C:CA	donor_gain	1.0000

AlphaMissense

3238 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:112710539:A:G	W431R	1.000
1:112710539:A:T	W431R	1.000
1:112710206:G:A	S492F	0.999
1:112710212:T:A	D490V	0.999
1:112710212:T:G	D490A	0.999
1:112710215:T:A	D489V	0.999
1:112710215:T:G	D489A	0.999
1:112710537:C:A	W431C	0.999
1:112710537:C:G	W431C	0.999
1:112710544:C:T	G429D	0.999
1:112710547:T:A	D428V	0.999
1:112710547:T:G	D428A	0.999
1:112710820:C:G	R381P	0.999
1:112711267:A:G	W349R	0.999
1:112711267:A:T	W349R	0.999
1:112711287:C:G	R342P	0.999
1:112711349:G:C	F321L	0.999
1:112711349:G:T	F321L	0.999
1:112711351:A:G	F321L	0.999
1:112712351:T:A	D279V	0.999
1:112712351:T:G	D279A	0.999
1:112713576:T:G	D121A	0.999
1:112713593:C:A	K115N	0.999
1:112713593:C:G	K115N	0.999
1:112713602:A:C	N112K	0.999
1:112713602:A:T	N112K	0.999
1:112710203:A:T	V493D	0.998
1:112710206:G:T	S492Y	0.998
1:112710213:C:G	D490H	0.998
1:112710214:A:C	D489E	0.998

dbSNP variants (sampled 300 via entrez): RS1000424483 (1:112716056 T>G), RS1000595945 (1:112711697 T>G), RS1000807781 (1:112717122 A>C), RS1001131509 (1:112715073 G>A), RS1001155217 (1:112717298 G>A,C), RS1001859887 (1:112716681 G>A), RS1001921219 (1:112715473 G>A,C), RS1002039649 (1:112716033 T>C), RS1002313704 (1:112716367 G>C), RS1002318508 (1:112711077 G>A), RS1002525643 (1:112714434 G>A), RS1002531802 (1:112713125 G>A), RS1002537856 (1:112716323 G>A), RS1002991691 (1:112714200 C>T), RS1003881672 (1:112716315 C>A,T)

Disease associations

OMIM: gene MIM:609957 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST007876_66	Estimated glomerular filtration rate	4.000000e-16
GCST008058_177	Estimated glomerular filtration rate	6.000000e-33
GCST008059_130	Estimated glomerular filtration rate	6.000000e-34
GCST008064_31	Chronic kidney disease	2.000000e-06
GCST008745_85	Estimated glomerular filtration rate in non-diabetics	4.000000e-08
GCST008747_1	Estimated glomerular filtration rate	2.000000e-25
GCST008747_61	Estimated glomerular filtration rate	9.000000e-18
GCST010696_10	Cortical thickness (min-P)	6.000000e-41
GCST010697_23	Cortical surface area (min-P)	1.000000e-08
GCST010698_26	Subcortical volume (min-P)	2.000000e-08
GCST010699_12	Brain morphology (min-P)	2.000000e-10
GCST010700_13	Cortical thickness (MOSTest)	8.000000e-13
GCST010701_138	Cortical surface area (MOSTest)	9.000000e-10
GCST010702_169	Subcortical volume (MOSTest)	2.000000e-17
GCST010703_263	Brain morphology (MOSTest)	3.000000e-13
GCST90000025_763	Appendicular lean mass	4.000000e-13

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	8
entinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Aflatoxin B1	decreases methylation, increases expression	2
OTX015	increases expression	1
FR900359	increases phosphorylation	1
mivebresib	increases expression	1
methyleugenol	increases expression	1
propionaldehyde	increases expression	1
potassium perchlorate	decreases expression	1
trichostatin A	affects expression	1
butyraldehyde	increases expression	1
pentanal	increases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
Acetaminophen	increases expression	1
Aldehydes	increases expression	1
Benzo(a)pyrene	increases expression	1
Carbamazepine	affects expression	1
Cisplatin	affects cotreatment, increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Diazinon	increases methylation	1
Estradiol	increases expression	1
Ethinyl Estradiol	increases expression	1
Lead	affects expression	1
Selenium	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TF44	HAP1 PPM1J (-) 1	Cancer cell line	Male
CVCL_TF45	HAP1 PPM1J (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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