PPM1N

Summary

PPM1N (protein phosphatase, Mg2+/Mn2+ dependent 1N (putative), HGNC:26845) is a protein-coding gene on chromosome 19q13.32, encoding Probable protein phosphatase 1N (Q8N819).

Predicted to enable protein serine/threonine phosphatase activity. Predicted to be involved in positive regulation of canonical Wnt signaling pathway and regulation of canonical NF-kappaB signal transduction. Predicted to be active in cytosol and nucleus.

Source: NCBI Gene 147699 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 80 total
• MANE Select transcript: NM_001080401

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26845
Approved symbol	PPM1N
Name	protein phosphatase, Mg2+/Mn2+ dependent 1N (putative)
Location	19q13.32
Locus type	gene with protein product
Status	Approved
Aliases	FLJ40125
Ensembl gene	ENSG00000213889
Ensembl biotype	protein_coding
Entrez	147699

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 nonsense_mediated_decay

ENST00000396735, ENST00000396736, ENST00000396737, ENST00000401593, ENST00000401705, ENST00000415077, ENST00000451287, ENST00000456399

RefSeq mRNA: 1 — MANE Select: NM_001080401 NM_001080401

CCDS: CCDS46115

Canonical transcript exons

ENST00000451287 — 5 exons

Exon	Start	End
ENSE00001560351	45502017	45502513
ENSE00002323148	45498443	45499411
ENSE00003524748	45499949	45500066
ENSE00003525352	45500650	45500710
ENSE00003601055	45500456	45500561

Expression profiles

Bgee: expression breadth ubiquitous, 159 present calls, max score 84.03.

FANTOM5 (CAGE): breadth broad, TPM avg 1.4529 / max 38.1072, expressed in 695 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176483	0.4709	235
176482	0.3833	189
176485	0.3122	132
208864	0.1371	71
176486	0.0441	17
176487	0.0408	18
176484	0.0388	11
176488	0.0257	9

Top tissues by expression

253 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	84.03	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.55	gold quality
monocyte	CL:0000576	81.59	gold quality
leukocyte	CL:0000738	81.26	gold quality
granulocyte	CL:0000094	81.15	gold quality
spleen	UBERON:0002106	77.84	gold quality
lower esophagus mucosa	UBERON:0035834	77.29	gold quality
buccal mucosa cell	CL:0002336	75.47	gold quality
pancreatic ductal cell	CL:0002079	72.35	silver quality
ileal mucosa	UBERON:0000331	72.25	gold quality
blood	UBERON:0000178	72.17	gold quality
nucleus accumbens	UBERON:0001882	69.27	gold quality
skin of abdomen	UBERON:0001416	68.97	gold quality
vermiform appendix	UBERON:0001154	68.24	gold quality
esophagus mucosa	UBERON:0002469	67.93	gold quality
putamen	UBERON:0001874	67.84	gold quality
anterior cingulate cortex	UBERON:0009835	67.82	gold quality
stromal cell of endometrium	CL:0002255	67.63	gold quality
skin of leg	UBERON:0001511	67.28	gold quality
lymph node	UBERON:0000029	67.27	gold quality
esophagus	UBERON:0001043	66.88	gold quality
caudate nucleus	UBERON:0001873	66.58	gold quality
apex of heart	UBERON:0002098	66.48	gold quality
omental fat pad	UBERON:0010414	66.43	gold quality
muscle layer of sigmoid colon	UBERON:0035805	66.37	gold quality
peritoneum	UBERON:0002358	66.36	gold quality
lower esophagus	UBERON:0013473	66.16	gold quality
lower esophagus muscularis layer	UBERON:0035833	66.12	gold quality
bone marrow cell	CL:0002092	66.09	silver quality
nasal cavity epithelium	UBERON:0005384	65.94	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-ENAD-17	yes	586.68
E-GEOD-76312	yes	29.44
E-ANND-3	yes	4.29

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

41 targeting PPM1N, 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-1252-5P	100.00	69.80	2774
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-4677-3P	99.49	67.91	1246
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-6839-3P	99.39	68.86	1301
HSA-MIR-5683	99.36	68.59	2083
HSA-MIR-4427	99.34	70.33	1854
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-1253	99.12	67.08	1688
HSA-MIR-155-3P	99.03	67.99	924
HSA-MIR-629-5P	98.78	68.72	1032
HSA-MIR-655-5P	98.74	65.93	888
HSA-MIR-34B-3P	98.70	67.40	1171
HSA-MIR-6868-3P	98.63	69.64	2259
HSA-MIR-9500	98.62	66.54	1845
HSA-MIR-6873-5P	98.45	66.14	1417

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	Ppm1n	ENSMUSG00000030402
rattus_norvegicus	Ppm1n	ENSRNOG00000058133
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), PPM1J (ENSG00000155367), PPM1L (ENSG00000163590), PPM1K (ENSG00000163644), PPM1M (ENSG00000164088), PDP1 (ENSG00000164951), PPM1D (ENSG00000170836), PDP2 (ENSG00000172840), PPM1E (ENSG00000175175), PP2D1 (ENSG00000183977)

Protein

Protein identifiers

Probable protein phosphatase 1N — Q8N819 (reviewed: Q8N819)

All UniProt accessions (5): A8MXX7, B5MCQ2, E7ENL9, Q8N819, H7C347

UniProt curated annotations — full annotation on UniProt →

Cofactor. Binds 2 magnesium or manganese ions per subunit.

Similarity. Belongs to the PP2C family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8N819-1	1	yes
Q8N819-2	2
Q8N819-3	3

RefSeq proteins (1): NP_001073870* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001932	PPM-type_phosphatase-like_dom	Domain
IPR012911	PP2C_C	Domain
IPR015655	PP2C	Family
IPR036457	PPM-type-like_dom_sf	Homologous_superfamily
IPR036580	PP2C_C_sf	Homologous_superfamily

Pfam: PF00481, PF07830

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 (13 total): binding site 5, splice variant 3, region of interest 2, chain 1, domain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N819-F1	87.36	0.78

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (5): 103; 103; 104; 274; 317

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 74 (showing top): GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_CANONICAL_WNT_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_CANONICAL_WNT_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_WNT_SIGNALING_PATHWAY, CCCNNGGGAR_OLF1_01, CP2_01, GOMF_MAGNESIUM_ION_BINDING, GOMF_MANGANESE_ION_BINDING, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS, GGGGCCC_MIR296, GOMF_PROTEIN_SERINE_THREONINE_PHOSPHATASE_ACTIVITY, GOMF_PHOSPHORIC_ESTER_HYDROLASE_ACTIVITY, MEISSNER_NPC_HCP_WITH_H3K27ME3, MEISSNER_BRAIN_HCP_WITH_H3K27ME3

GO Biological Process (3): regulation of canonical NF-kappaB signal transduction (GO:0043122), positive regulation of canonical Wnt signaling pathway (GO:0090263), protein dephosphorylation (GO:0006470)

GO Molecular Function (6): magnesium ion binding (GO:0000287), protein serine/threonine phosphatase activity (GO:0004722), manganese ion binding (GO:0030145), phosphoprotein phosphatase activity (GO:0004721), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (2): nucleus (GO:0005634), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
canonical NF-kappaB signal transduction	1
regulation of intracellular signal transduction	1
positive regulation of Wnt signaling pathway	1
canonical Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
dephosphorylation	1
protein modification process	1
metal ion binding	1
phosphoprotein phosphatase activity	1
transition metal ion binding	1
phosphatase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
cation binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1455 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPM1N	TMEM14A	Q9Y6G1	568
PPM1N	FGD6	Q6ZV73	520
PPM1N	COBLL1	Q53SF7	519
PPM1N	GCSAM	Q8N6F7	508
PPM1N	CLNK	Q7Z7G1	506
PPM1N	GGT5	P36269	471
PPM1N	UPK3A	O75631	459
PPM1N	PACSIN1	Q9BY11	451
PPM1N	MCEMP1	Q8IX19	432
PPM1N	PRAM1	Q96QH2	427
PPM1N	LRIT2	A6NDA9	412
PPM1N	TTC17	Q96AE7	401
PPM1N	MS4A10	Q96PG2	400
PPM1N	LPAR2	Q9HBW0	398
PPM1N	KAAG1	Q9UBP8	394

IntAct

1 interactions, top by confidence:

BioGRID (3): PPM1N (Proximity Label-MS), PPM1N (Affinity Capture-RNA), UBE2D2 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A2A9Q0, A6NED2, A9JSM3, B0BNK7, B7Z1M9, C9JI98, D2HFT7, D4A2Q0, O94819, P0C7J6, P0C7L8, P0CG09, P0CG25, P0DKB5, Q0MW30, Q1RMS4, Q2I0M4, Q2M3D2, Q2MJR0, Q2WF71, Q32NY4, Q5EBP3, Q5PQP9, Q6NY19, Q6P6N5, Q6PJG9, Q6UKI2, Q6ZW31, Q7Z736, Q86UD0, Q8BGL1, Q8BLY3, Q8BNW9, Q8BRJ4, Q8N144, Q8N239, Q8N4B1, Q8N819, Q8QZV0, Q96BM1

Diamond homologs: A0A7U2MSD6, A0BLX0, A0BQL0, A0CUB5, A0DSB3, A0DTY1, A3A8Q4, A3A8W2, A3A8W6, A5PJZ2, F1LNI5, G0RT93, O04719, O15355, O15743, O62829, O62830, O75688, O80871, O81716, P20650, P34221, P35813, P35814, P35815, P36993, P38089, P39966, P40371, P49443, P49444, P49593, P49595, P49596, P49597, P49598, P79126, P93006, Q09172, Q09173

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	68
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2179 predictions. Top by Δscore:

Variant	Effect	Δscore
19:45488985:CC:C	acceptor_gain	1.0000
19:45488986:CC:C	acceptor_gain	1.0000
19:45488986:CCT:C	acceptor_loss	1.0000
19:45488988:T:G	acceptor_loss	1.0000
19:45489344:A:AC	donor_gain	1.0000
19:45489345:C:CC	donor_gain	1.0000
19:45495003:CTC:C	acceptor_gain	1.0000
19:45495005:CCTGC:C	acceptor_loss	1.0000
19:45495006:CTGCA:C	acceptor_loss	1.0000
19:45495091:TTACC:T	donor_loss	1.0000
19:45495092:TAC:T	donor_loss	1.0000
19:45495094:C:CA	donor_loss	1.0000
19:45495094:CCTT:C	donor_gain	1.0000
19:45495140:C:CC	acceptor_gain	1.0000
19:45496902:T:C	donor_gain	1.0000
19:45500562:G:GG	donor_gain	1.0000
19:45488844:CCA:C	donor_loss	0.9900
19:45488845:CA:C	donor_loss	0.9900
19:45488846:ACC:A	donor_loss	0.9900
19:45488847:CC:C	donor_loss	0.9900
19:45488848:C:G	donor_loss	0.9900
19:45488982:AGGCC:A	acceptor_gain	0.9900
19:45488983:GGCC:G	acceptor_gain	0.9900
19:45488984:GCC:G	acceptor_gain	0.9900
19:45488985:CCC:C	acceptor_gain	0.9900
19:45488987:C:CC	acceptor_gain	0.9900
19:45489379:G:GA	donor_gain	0.9900
19:45489398:AAAC:A	donor_gain	0.9900
19:45493168:C:A	donor_gain	0.9900
19:45494264:T:TA	donor_gain	0.9900

AlphaMissense

2719 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:45499189:G:C	K239N	0.996
19:45499189:G:T	K239N	0.996
19:45499188:A:T	K239M	0.984
19:45499290:C:T	S273F	0.982
19:45499014:G:T	G181V	0.979
19:45499104:T:C	I211T	0.975
19:45499274:T:C	F268L	0.972
19:45499276:C:A	F268L	0.972
19:45499276:C:G	F268L	0.972
19:45499100:C:A	R210S	0.971
19:45498902:T:C	F144L	0.970
19:45498904:C:A	F144L	0.970
19:45498904:C:G	F144L	0.970
19:45499290:C:A	S273Y	0.970
19:45498780:A:T	D103V	0.969
19:45499188:A:C	K239T	0.968
19:45498713:G:C	D81H	0.967
19:45499173:G:T	G234V	0.966
19:45499177:C:A	D235E	0.966
19:45499177:C:G	D235E	0.966
19:45498915:A:T	D148V	0.965
19:45499962:A:T	N318I	0.964
19:45499980:T:A	V324D	0.964
19:45498825:T:C	L118S	0.963
19:45499187:A:G	K239E	0.963
19:45499968:C:T	T320I	0.963
19:45500650:G:C	K388N	0.963
19:45500650:G:T	K388N	0.963
19:45499236:C:A	P255Q	0.962
19:45499018:C:A	D182E	0.961

dbSNP variants (sampled 300 via entrez): RS1000057452 (19:45501428 A>G), RS1000306761 (19:45501879 A>C,G), RS1000534620 (19:45501710 G>A), RS1001466568 (19:45502989 A>T), RS1001731680 (19:45501805 G>A), RS1001750008 (19:45501025 A>G), RS1003404275 (19:45500023 G>A), RS1004077083 (19:45496554 A>G), RS1004149047 (19:45496827 G>A), RS1004275341 (19:45501872 G>A,T), RS1005084582 (19:45497596 G>T), RS1006323354 (19:45500479 C>T), RS1006422068 (19:45500804 A>C), RS1008749688 (19:45497091 C>A), RS1009001078 (19:45498876 G>A)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:604805

GenCC curated gene-disease

Mondo (1): hereditary spastic paraplegia 12 (MONDO:0011489)

Orphanet (1): Autosomal dominant spastic paraplegia type 12 (Orphanet:100993)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007827_3	Alzheimer’s disease or HDL levels (pleiotropy)	1.000000e-97

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537484	Spastic paraplegia 12, autosomal dominant (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	4
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
sotorasib	affects cotreatment, decreases expression	1
bisphenol A	decreases methylation	1
terbufos	increases methylation	1
arsenite	increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	increases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Carbamazepine	affects expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Fonofos	increases methylation	1
Parathion	increases methylation	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Antirheumatic Agents	decreases expression	1
Copper Sulfate	increases expression	1
Lactic Acid	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_TF51	HAP1 PPM1N (-) 1	Cancer cell line	Male
CVCL_TF52	HAP1 PPM1N (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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