PP2D1

Summary

PP2D1 (protein phosphatase 2C like domain containing 1, HGNC:28406) is a protein-coding gene on chromosome 3p24.3, encoding Protein phosphatase 2C-like domain-containing protein 1 (A8MPX8).

Predicted to enable protein serine/threonine phosphatase activity. Predicted to be involved in negative regulation of MAPK cascade and signal transduction. Predicted to be active in cytoplasm and nucleus.

Source: NCBI Gene 151649 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 7 total
• MANE Select transcript: NM_001252657

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28406
Approved symbol	PP2D1
Name	protein phosphatase 2C like domain containing 1
Location	3p24.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ25449
Ensembl gene	ENSG00000183977
Ensembl biotype	protein_coding
OMIM	621037
Entrez	151649

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 1 nonsense_mediated_decay, 1 protein_coding, 1 retained_intron

ENST00000333083, ENST00000389050, ENST00000461033

RefSeq mRNA: 1 — MANE Select: NM_001252657 NM_001252657

CCDS: CCDS58817

Canonical transcript exons

ENST00000389050 — 3 exons

Exon	Start	End
ENSE00001317787	20001030	20002096
ENSE00001504765	19985346	19986182
ENSE00001860873	20012050	20012264

Expression profiles

Bgee: expression breadth ubiquitous, 158 present calls, max score 91.34.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0320 / max 29.7716, expressed in 3 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
41415	0.0161	3
41413	0.0079	3
41414	0.0079	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	91.34	gold quality
left testis	UBERON:0004533	81.62	gold quality
right testis	UBERON:0004534	80.78	gold quality
testis	UBERON:0000473	79.79	gold quality
buccal mucosa cell	CL:0002336	69.34	silver quality
monocyte	CL:0000576	67.77	gold quality
leukocyte	CL:0000738	66.07	gold quality
tendon of biceps brachii	UBERON:0008188	62.73	gold quality
smooth muscle tissue	UBERON:0001135	62.03	gold quality
islet of Langerhans	UBERON:0000006	60.89	gold quality
bone marrow cell	CL:0002092	59.65	gold quality
right lung	UBERON:0002167	59.20	gold quality
mucosa of stomach	UBERON:0001199	58.79	gold quality
tendon	UBERON:0000043	58.46	silver quality
skin of abdomen	UBERON:0001416	58.11	gold quality
left uterine tube	UBERON:0001303	57.98	gold quality
skin of leg	UBERON:0001511	57.94	gold quality
rectum	UBERON:0001052	57.83	gold quality
stromal cell of endometrium	CL:0002255	57.68	gold quality
ectocervix	UBERON:0012249	57.46	gold quality
pancreas	UBERON:0001264	57.21	gold quality
tibial artery	UBERON:0007610	57.00	gold quality
popliteal artery	UBERON:0002250	56.97	gold quality
upper lobe of left lung	UBERON:0008952	56.72	gold quality
aorta	UBERON:0000947	56.71	gold quality
ascending aorta	UBERON:0001496	56.67	gold quality
thoracic aorta	UBERON:0001515	56.60	gold quality
body of pancreas	UBERON:0001150	56.50	gold quality
descending thoracic aorta	UBERON:0002345	56.46	gold quality
upper lobe of lung	UBERON:0008948	56.30	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.01

Regulation

Is transcription factor: no

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pp2d1	ENSMUSG00000044957
rattus_norvegicus	Pp2d1	ENSRNOG00000004719
drosophila_melanogaster	Pdp	FBGN0029958
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		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), PPM1N (ENSG00000213889)

Protein

Protein identifiers

Protein phosphatase 2C-like domain-containing protein 1 — A8MPX8 (reviewed: A8MPX8)

All UniProt accessions (1): A8MPX8

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the PP2C family.

Isoforms (3)

UniProt ID	Names	Canonical?
A8MPX8-1	1	yes
A8MPX8-2	2
A8MPX8-3	3

RefSeq proteins (1): NP_001239586* (*=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

UniProt features (11 total): splice variant 4, sequence variant 3, 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-A8MPX8-F1	71.02	0.40

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 16 (showing top): GOBP_NEGATIVE_REGULATION_OF_MAPK_CASCADE, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_DN, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS, GOMF_PROTEIN_SERINE_THREONINE_PHOSPHATASE_ACTIVITY, GOMF_PHOSPHORIC_ESTER_HYDROLASE_ACTIVITY, chr3p24, GOMF_PHOSPHOPROTEIN_PHOSPHATASE_ACTIVITY, GOMF_PHOSPHATASE_ACTIVITY, SMTTTTGT_UNKNOWN, DESCARTES_MAIN_FETAL_CORNEAL_AND_CONJUNCTIVAL_EPITHELIAL_CELLS, GOBP_MAPK_CASCADE, GOBP_NEGATIVE_REGULATION_OF_CELL_COMMUNICATION, GSE19198_1H_VS_6H_IL21_TREATED_TCELL_UP, GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_STIMULUS

GO Biological Process (3): signal transduction (GO:0007165), negative regulation of MAPK cascade (GO:0043409), protein dephosphorylation (GO:0006470)

GO Molecular Function (1): protein serine/threonine phosphatase activity (GO:0004722)

GO Cellular Component (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
MAPK cascade	1
regulation of MAPK cascade	1
negative regulation of intracellular signal transduction	1
dephosphorylation	1
protein modification process	1
phosphoprotein phosphatase activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

957 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PP2D1	SPINT4	Q6UDR6	507
PP2D1	PPTC7	Q8NI37	475
PP2D1	HCFC1R1	Q9NWW0	458
PP2D1	SAXO1	Q8IYX7	456
PP2D1	D6RAR5	D6RAR5	411
PP2D1	PPM1M	Q96MI6	392
PP2D1	PPM1J	Q5JR12	390
PP2D1	SIAH3	Q8IW03	388
PP2D1	ZMYM5	Q9UJ78	379
PP2D1	ABHD17B	Q5VST6	371
PP2D1	LSM5	Q9Y4Y9	360
PP2D1	PPP1R1C	Q8WVI7	348
PP2D1	ALKBH7	Q9BT30	339
PP2D1	TRIM67	Q6ZTA4	331
PP2D1	NUDT11	Q96G61	328

IntAct

3 interactions, top by confidence:

A	B	Type	Score
PP2D1	iglC2	psi-mi:“MI:0915”(physical association)	0.370
M		psi-mi:“MI:0914”(association)	0.350

BioGRID (3): PP2D1 (Reconstituted Complex), PP2D1 (Synthetic Lethality), APP (Reconstituted Complex)

ESM2 similar proteins: A0JMR6, A2RRS8, A6NFN9, A8MPX8, B1ANS9, O15297, O75747, P25022, P79457, Q08AW4, Q14680, Q14AW5, Q15052, Q2IBB1, Q2IBB4, Q2IBG0, Q2QL84, Q2QLH1, Q3MJ13, Q3US16, Q4R3G4, Q4R7Q1, Q5H913, Q5JTW2, Q5R5T0, Q5R6E1, Q5RFQ4, Q5SUS0, Q5XGI3, Q5XX13, Q5XXR3, Q692V3, Q6P2S7, Q6P3V7, Q7XVF9, Q86VS3, Q8BVT6, Q8C0W1, Q8C5W4, Q8IV35

Diamond homologs: A5PJZ2, A6K136, A8MPX8, O04719, O60346, O64583, P40371, P49595, P49597, P49598, Q0D673, Q0JAA0, Q2PC20, Q2QWE3, Q4PSE8, Q53Q11, Q5R522, Q5SGD2, Q65XK7, Q6EN45, Q6L4R7, Q6L5C4, Q6L5H6, Q6ZVD8, Q7XQU7, Q7XR06, Q8BVT6, Q8BXN7, Q8CHE4, Q8LAY8, Q8N3J5, Q93YW5, Q9FIF5, Q9LDA7, Q9LME4, Q9LNW3, Q9S9Z7, Q9WTR8, Q9XEE8, Q9ZW21

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	2
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

740 predictions. Top by Δscore:

Variant	Effect	Δscore
3:19983702:TTTCA:T	acceptor_loss	0.9900
3:19983703:TTCAG:T	acceptor_loss	0.9900
3:19983704:TCAG:T	acceptor_loss	0.9900
3:19983705:CA:C	acceptor_loss	0.9900
3:19983706:A:AG	acceptor_gain	0.9900
3:19983706:AGCT:A	acceptor_loss	0.9900
3:19983707:G:GG	acceptor_gain	0.9900
3:19983707:GCT:G	acceptor_gain	0.9900
3:19983707:GCTA:G	acceptor_gain	0.9900
3:19983707:GCTAA:G	acceptor_gain	0.9900
3:20001498:C:CT	acceptor_gain	0.9900
3:20002095:CT:C	acceptor_gain	0.9900
3:19980095:G:T	donor_gain	0.9800
3:20001495:C:CT	acceptor_gain	0.9800
3:20001507:C:CT	acceptor_gain	0.9800
3:20002093:CACT:C	acceptor_gain	0.9800
3:19983707:GC:G	acceptor_gain	0.9700
3:20001486:CGTGA:C	acceptor_gain	0.9700
3:20008055:G:C	donor_gain	0.9700
3:20001508:A:T	acceptor_gain	0.9600
3:20008132:CG:C	donor_gain	0.9600
3:19986180:TACCT:T	acceptor_loss	0.9500
3:19986181:ACC:A	acceptor_loss	0.9500
3:19986182:CCTAA:C	acceptor_loss	0.9500
3:19986183:C:CG	acceptor_loss	0.9500
3:19986184:T:G	acceptor_loss	0.9500
3:20001499:A:T	acceptor_gain	0.9500
3:20001937:C:A	donor_gain	0.9500
3:19982668:G:GG	donor_gain	0.9400
3:20008045:A:AC	donor_gain	0.9400

AlphaMissense

4174 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:20001039:C:G	A361P	0.980
3:19985901:A:G	W458R	0.977
3:19985901:A:T	W458R	0.977
3:20001171:A:G	C317R	0.974
3:20001038:G:T	A361E	0.972
3:19985924:A:G	L450P	0.971
3:19985927:A:G	F449S	0.971
3:19986164:A:G	L370S	0.971
3:19985459:G:T	A605D	0.970
3:19985471:A:G	L601P	0.970
3:19985492:G:T	A594D	0.970
3:19985951:A:T	V441D	0.970
3:19985899:C:A	W458C	0.968
3:19985899:C:G	W458C	0.968
3:20001047:A:G	L358S	0.968
3:19985479:G:C	S598R	0.967
3:19985479:G:T	S598R	0.967
3:19985481:T:G	S598R	0.967
3:19985934:A:G	C447R	0.966
3:19985426:A:T	V616D	0.964
3:20001250:A:C	F290L	0.964
3:20001250:A:T	F290L	0.964
3:20001252:A:G	F290L	0.964
3:20001255:C:G	A289P	0.962
3:19985471:A:T	L601H	0.961
3:20001041:A:T	V360D	0.959
3:19985916:C:G	A453P	0.958
3:20001452:A:G	L223P	0.957
3:20001195:A:G	W309R	0.956
3:20001195:A:T	W309R	0.956

dbSNP variants (sampled 300 via entrez): RS1000106887 (3:19997518 C>G), RS1000352050 (3:20010941 G>A), RS1000403071 (3:20002265 G>T), RS1000465847 (3:19986828 C>A,G,T), RS1000544918 (3:19995867 A>G), RS1000547223 (3:19995598 G>A), RS1000842221 (3:20005638 T>C), RS1001056060 (3:19992689 A>G), RS1001112039 (3:19999153 C>T), RS1001247610 (3:20006676 G>A), RS1001256803 (3:20013300 C>A,G,T), RS1001309721 (3:20009951 A>C,G), RS1001336915 (3:20005366 C>T), RS1001347684 (3:20003933 A>C), RS1001383197 (3:19996671 G>C)

Disease associations

OMIM: gene MIM:621037 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003181_1	Staphylococcus aureus nasal carriage (intermittent)	9.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007758	intermittent Staphylococcus aureus carrier status

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
jinfukang	decreases expression	1
Lipopolysaccharides	increases expression, affects response to substance	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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