PPM1M

Summary

PPM1M (protein phosphatase, Mg2+/Mn2+ dependent 1M, HGNC:26506) is a protein-coding gene on chromosome 3p21.2, encoding Protein phosphatase 1M (Q96MI6).

Predicted to enable [pyruvate dehydrogenase (acetyl-transferring)]-phosphatase activity and manganese ion binding activity. Predicted to be involved in protein dephosphorylation and signal transduction. Predicted to be located in nucleus. Predicted to be active in mitochondrion.

Source: NCBI Gene 132160 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 70 total
• MANE Select transcript: NM_144641

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26506
Approved symbol	PPM1M
Name	protein phosphatase, Mg2+/Mn2+ dependent 1M
Location	3p21.2
Locus type	gene with protein product
Status	Approved
Aliases	PP2Ceta, FLJ32332
Ensembl gene	ENSG00000164088
Ensembl biotype	protein_coding
OMIM	608979
Entrez	132160

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 10 protein_coding, 4 retained_intron

ENST00000296487, ENST00000323588, ENST00000409502, ENST00000443681, ENST00000457454, ENST00000467471, ENST00000472955, ENST00000482724, ENST00000489606, ENST00000855772, ENST00000933491, ENST00000970938, ENST00000970939, ENST00000970940

RefSeq mRNA: 2 — MANE Select: NM_144641 NM_001122870, NM_144641

CCDS: CCDS46840, CCDS93282

Canonical transcript exons

ENST00000323588 — 10 exons

Exon	Start	End
ENSE00001578510	52249670	52250599
ENSE00002243554	52245759	52246048
ENSE00003498118	52246974	52247228
ENSE00003499252	52249174	52249322
ENSE00003533444	52248637	52248700
ENSE00003596357	52247682	52247794
ENSE00003690324	52246695	52246812
ENSE00003807389	52248956	52249063
ENSE00003890896	52248153	52248237
ENSE00003891723	52248335	52248453

Expression profiles

Bgee: expression breadth ubiquitous, 212 present calls, max score 97.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.3043 / max 297.4962, expressed in 1710 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36827	10.3558	1695
36830	0.5027	239
36829	0.1994	89
202766	0.1037	56
36828	0.0713	35
36832	0.0412	17
36831	0.0301	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	97.10	gold quality
leukocyte	CL:0000738	95.79	gold quality
monocyte	CL:0000576	95.76	gold quality
blood	UBERON:0000178	93.43	gold quality
spleen	UBERON:0002106	92.98	gold quality
vermiform appendix	UBERON:0001154	92.47	gold quality
descending thoracic aorta	UBERON:0002345	91.69	gold quality
right coronary artery	UBERON:0001625	91.53	gold quality
right lung	UBERON:0002167	91.53	gold quality
endocervix	UBERON:0000458	91.39	gold quality
thoracic aorta	UBERON:0001515	91.14	gold quality
ascending aorta	UBERON:0001496	91.10	gold quality
lymph node	UBERON:0000029	90.82	gold quality
ectocervix	UBERON:0012249	90.44	gold quality
left coronary artery	UBERON:0001626	90.24	gold quality
body of uterus	UBERON:0009853	90.19	gold quality
upper lobe of left lung	UBERON:0008952	89.90	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	89.75	gold quality
mucosa of stomach	UBERON:0001199	89.69	gold quality
smooth muscle tissue	UBERON:0001135	89.66	gold quality
aorta	UBERON:0000947	89.65	gold quality
right ovary	UBERON:0002118	89.64	gold quality
bone marrow cell	CL:0002092	89.63	gold quality
tibial nerve	UBERON:0001323	89.61	gold quality
stromal cell of endometrium	CL:0002255	89.54	gold quality
left uterine tube	UBERON:0001303	89.35	gold quality
coronary artery	UBERON:0001621	89.30	gold quality
apex of heart	UBERON:0002098	89.27	gold quality
lower esophagus	UBERON:0013473	89.16	gold quality
lower esophagus muscularis layer	UBERON:0035833	89.16	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.52

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

65 targeting PPM1M, 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-6851-5P	100.00	65.63	1294
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-4687-3P	99.48	66.41	968
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-7854-3P	99.08	66.26	1117
HSA-MIR-5587-5P	99.07	68.58	838

Literature-anchored findings (GeneRIF, showing 3)

• PP2Ceta-2 inhibits the IL-1-NF-kappaB signalling pathway by selectively dephosphorylating IKKbeta. (PMID:19594441)
• Novel progressive acrodysostosis-like skeletal dysplasia, cerebellar atrophy, and ichthyosis. (PMID:32783359)
• Exploring the immunological role and prognostic potential of PPM1M in pan-cancer. (PMID:36961170)

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	Ppm1m	ENSMUSG00000020253
rattus_norvegicus	Ppm1m	ENSRNOG00000046535
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), PDP1 (ENSG00000164951), PPM1D (ENSG00000170836), PDP2 (ENSG00000172840), PPM1E (ENSG00000175175), PP2D1 (ENSG00000183977), PPM1N (ENSG00000213889)

Protein

Protein identifiers

Protein phosphatase 1M — Q96MI6 (reviewed: Q96MI6)

Alternative names: Protein phosphatase 2C isoform eta

All UniProt accessions (3): Q96MI6, H7C3K4, H7C3S3

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus.

Cofactor. Binds 2 magnesium or manganese ions per subunit.

Similarity. Belongs to the PP2C family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q96MI6-5	5	yes
Q96MI6-1	1
Q96MI6-2	2
Q96MI6-3	3
Q96MI6-4	4

RefSeq proteins (2): NP_001116342, NP_653242* (*=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 (17 total): splice variant 8, compositionally biased region 3, binding site 3, chain 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96MI6-F1	86.21	0.71

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 (3): 125; 125; 126

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 69 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_DEPHOSPHORYLATION, GOBP_PROTEIN_DEPHOSPHORYLATION, MORI_MATURE_B_LYMPHOCYTE_UP, GAVIN_FOXP3_TARGETS_CLUSTER_T7, GOMF_MANGANESE_ION_BINDING, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS, GOMF_PROTEIN_SERINE_THREONINE_PHOSPHATASE_ACTIVITY, GOMF_PHOSPHORIC_ESTER_HYDROLASE_ACTIVITY, CHICAS_RB1_TARGETS_CONFLUENT, BRUINS_UVC_RESPONSE_LATE, GOMF_PHOSPHOPROTEIN_PHOSPHATASE_ACTIVITY, E2F1_UP.V1_UP, GCNP_SHH_UP_LATE.V1_DN

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

GO Molecular Function (6): [pyruvate dehydrogenase (acetyl-transferring)]-phosphatase activity (GO:0004741), manganese ion binding (GO:0030145), phosphoprotein phosphatase activity (GO:0004721), protein serine/threonine phosphatase activity (GO:0004722), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (2): nucleus (GO:0005634), mitochondrion (GO:0005739)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	2
dephosphorylation	1
protein modification process	1
protein serine/threonine phosphatase activity	1
transition metal ion binding	1
phosphatase activity	1
catalytic activity, acting on a protein	1
phosphoprotein phosphatase activity	1
catalytic activity	1
cation binding	1
cytoplasm	1

Protein interactions and networks

STRING

476 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPM1M	PPM1F	P49593	598
PPM1M	PPM1G	O15355	598
PPM1M	PPM1K	Q8N3J5	576
PPM1M	PPTC7	Q8NI37	555
PPM1M	PPM1D	O15297	527
PPM1M	NT5DC2	Q9H857	463
PPM1M	PTPRU	P78399	459
PPM1M	RILP	Q96NA2	442
PPM1M	PHLPP1	O60346	430
PPM1M	BCAR1	P56945	426
PPM1M	RILPL1	Q5EBL4	423
PPM1M	PPEF2	O14830	417
PPM1M	ACTN1	P12814	409
PPM1M	ITGA3	P26006	404
PPM1M	PLPP6	Q8IY26	395

IntAct

10 interactions, top by confidence:

A	B	Type	Score
MAD2L1	PPIP5K2	psi-mi:“MI:0914”(association)	0.530
VEGFB	LAMB2	psi-mi:“MI:0914”(association)	0.530
	RAB10	psi-mi:“MI:0203”(dephosphorylation reaction)	0.440
PPM1M	AATK	psi-mi:“MI:0915”(physical association)	0.370
PPM1M	ERBB3	psi-mi:“MI:0915”(physical association)	0.370
PPM1J	ACTR3	psi-mi:“MI:0914”(association)	0.350
PPM1M	HSPA8	psi-mi:“MI:0914”(association)	0.350
PPM1M	GAK	psi-mi:“MI:0914”(association)	0.350
VEGFB	NPC1	psi-mi:“MI:0914”(association)	0.350

BioGRID (53): PPM1M (Affinity Capture-MS), ZYG11B (Affinity Capture-MS), PPM1M (Two-hybrid), PPM1M (Two-hybrid), CDC37 (Affinity Capture-MS), STIP1 (Affinity Capture-MS), TPM4 (Affinity Capture-MS), PPM1M (Affinity Capture-RNA), HSPA2 (Affinity Capture-MS), CCT6A (Affinity Capture-MS), CCT4 (Affinity Capture-MS), CCT2 (Affinity Capture-MS), ZYG11B (Affinity Capture-MS), TCP1 (Affinity Capture-MS), CCT8 (Affinity Capture-MS)

ESM2 similar proteins: A1A4I4, A6QP75, C9J798, E1BE10, E2RD63, O35465, O43374, O95294, P29376, P30530, P49593, Q14318, Q16512, Q17QS4, Q1LZ97, Q2TBI8, Q3B7U9, Q4FZD7, Q58D06, Q5SWZ9, Q5T9C9, Q6IN84, Q6P5Z2, Q6P9U1, Q6RFH5, Q86UR1, Q8BNV1, Q8CGA0, Q8IZ69, Q8N1F8, Q8N2A8, Q8N9H8, Q8NE01, Q8TCX5, Q8TDF6, Q8WXI3, Q920N2, Q925B4, Q969S8, Q96DC7

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, A0A7U2MSD6, A3A8W2, A6K136, F1LNI5, G0RT93, O04719, O15355, O62830, O64583, O75688, O82637, P34221, P35815, P38089, P39966, P49595, P49597

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	55
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1659 predictions. Top by Δscore:

Variant	Effect	Δscore
3:52246049:G:GG	donor_gain	1.0000
3:52246811:AGGTG:A	donor_loss	1.0000
3:52246813:G:GC	donor_loss	1.0000
3:52246814:T:A	donor_loss	1.0000
3:52246972:A:AG	acceptor_gain	1.0000
3:52246973:G:GG	acceptor_gain	1.0000
3:52247209:A:T	donor_gain	1.0000
3:52247224:A:T	donor_gain	1.0000
3:52247227:GT:G	donor_gain	1.0000
3:52247678:CCAGG:C	acceptor_loss	1.0000
3:52247679:CAG:C	acceptor_loss	1.0000
3:52247680:A:AG	acceptor_gain	1.0000
3:52247680:A:AT	acceptor_loss	1.0000
3:52247680:AG:A	acceptor_gain	1.0000
3:52247680:AGGAT:A	acceptor_gain	1.0000
3:52247681:G:GA	acceptor_gain	1.0000
3:52247681:GG:G	acceptor_gain	1.0000
3:52247681:GGAT:G	acceptor_gain	1.0000
3:52247681:GGATG:G	acceptor_gain	1.0000
3:52247791:GCAG:G	donor_gain	1.0000
3:52247795:G:GG	donor_gain	1.0000
3:52247796:T:G	donor_loss	1.0000
3:52248146:A:AG	acceptor_gain	1.0000
3:52248147:A:AG	acceptor_gain	1.0000
3:52248148:T:G	acceptor_gain	1.0000
3:52248149:CCAG:C	acceptor_loss	1.0000
3:52248150:CA:C	acceptor_loss	1.0000
3:52248151:A:AG	acceptor_gain	1.0000
3:52248151:AG:A	acceptor_gain	1.0000
3:52248151:AGG:A	acceptor_gain	1.0000

AlphaMissense

2975 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:52248368:T:C	F116L	0.998
3:52248370:C:A	F116L	0.998
3:52248370:C:G	F116L	0.998
3:52248383:T:C	F121L	0.996
3:52248385:C:A	F121L	0.996
3:52248385:C:G	F121L	0.996
3:52248452:T:A	W144R	0.996
3:52248452:T:C	W144R	0.996
3:52249246:T:A	W226R	0.994
3:52249246:T:C	W226R	0.994
3:52248987:G:C	R176P	0.993
3:52248190:A:C	S89R	0.992
3:52248192:C:A	S89R	0.992
3:52248192:C:G	S89R	0.992
3:52247790:A:C	S75R	0.991
3:52247792:C:A	S75R	0.991
3:52247792:C:G	S75R	0.991
3:52248369:T:C	F116S	0.991
3:52248384:T:C	F121S	0.989
3:52248963:T:C	L168S	0.989
3:52249044:T:C	F195S	0.989
3:52247737:C:A	A57D	0.988
3:52247769:T:G	Y68D	0.988
3:52247782:C:A	A72D	0.988
3:52248154:G:C	A77P	0.988
3:52248637:G:C	W144C	0.988
3:52248637:G:T	W144C	0.988
3:52249231:G:C	A221P	0.988
3:52247785:G:T	G73V	0.987
3:52248218:G:C	R98P	0.987

dbSNP variants (sampled 300 via entrez): RS1000174995 (3:52244711 G>A,T), RS1001077340 (3:52249126 G>T), RS1001524998 (3:52248075 G>A,C), RS1001849833 (3:52246620 T>C), RS1003882080 (3:52247959 G>A), RS1004134729 (3:52245502 C>G), RS1004259920 (3:52243966 C>T), RS1005207773 (3:52246594 C>A,T), RS1005764064 (3:52246937 G>A,C), RS1005986768 (3:52246190 C>T), RS1007609395 (3:52247604 G>A), RS1008660186 (3:52250146 C>T), RS1008776584 (3:52249949 C>G,T), RS1009560912 (3:52243865 T>C), RS1009880288 (3:52244664 C>T)

Disease associations

OMIM: gene MIM:608979 | disease phenotypes: MIM:612015

GenCC curated gene-disease

Mondo (1): RFT1-congenital disorder of glycosylation (MONDO:0012783)

Orphanet (1): RFT1-CDG (Orphanet:244310)

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001241_15	Bipolar disorder	2.000000e-06
GCST002149_14	Schizophrenia	1.000000e-08
GCST004521_123	Autism spectrum disorder or schizophrenia	3.000000e-12
GCST004521_201	Autism spectrum disorder or schizophrenia	4.000000e-08

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C567437	Congenital Disorder Of Glycosylation, Type In (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects expression, affects cotreatment, increases expression, decreases expression	4
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
bisphenol F	increases expression, affects cotreatment	1
triphenyl phosphate	affects expression	1
terbufos	decreases methylation	1
sodium arsenite	decreases expression	1
cobaltous chloride	affects expression	1
ferrous chloride	decreases expression	1
beta-methylcholine	affects expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	increases expression	1
Temozolomide	increases expression	1
Norethindrone Acetate	affects cotreatment, increases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Calcitriol	decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Cytarabine	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Diuron	decreases expression	1
Drugs, Chinese Herbal	increases expression	1
Fonofos	decreases methylation	1
Indomethacin	affects cotreatment, increases expression	1
Naphthoquinones	increases expression	1
Parathion	decreases methylation	1
Quercetin	increases expression	1
Silicon Dioxide	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TF50	HAP1 PPM1M (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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