PTPN20

Summary

PTPN20 (protein tyrosine phosphatase non-receptor type 20, HGNC:23423) is a protein-coding gene on chromosome 10q11.22, encoding Tyrosine-protein phosphatase non-receptor type 20 (Q4JDL3). Tyrosine-protein phosphatase targeted to sites of actin polymerization in response of varied extracellular stimuli.

The product of this gene belongs to the family of classical tyrosine-specific protein tyrosine phosphatases. Many protein tyrosine phosphatases have been shown to regulate fundamental cellular processes. The encoded protein appears to be targeted to sites of actin polymerization. A pseudogene of this gene has been defined on chromosome 10. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 26095 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 1 total
• MANE Select transcript: NM_001042357

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23423
Approved symbol	PTPN20
Name	protein tyrosine phosphatase non-receptor type 20
Location	10q11.22
Locus type	gene with protein product
Status	Approved
Aliases	bA42B19.1, DKFZP566K0524, bA142I17.1, CT126
Ensembl gene	ENSG00000204179
Ensembl biotype	protein_coding
OMIM	610630
Entrez	26095

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 31 protein_coding, 3 nonsense_mediated_decay, 1 retained_intron

ENST00000374218, ENST00000374339, ENST00000374342, ENST00000374346, ENST00000395721, ENST00000395722, ENST00000395725, ENST00000395727, ENST00000417004, ENST00000437863, ENST00000466912, ENST00000502254, ENST00000502705, ENST00000503851, ENST00000505814, ENST00000506080, ENST00000506881, ENST00000508357, ENST00000508602, ENST00000508715, ENST00000509599, ENST00000509774, ENST00000509900, ENST00000510335, ENST00000511769, ENST00000513156, ENST00000513159, ENST00000513266, ENST00000513756, ENST00000863830, ENST00000863831, ENST00000928031, ENST00000928032, ENST00000951656, ENST00000951657

RefSeq mRNA: 53 — MANE Select: NM_001042357 NM_001042357, NM_001042358, NM_001042359, NM_001042360, NM_001042361, NM_001042362, NM_001042363, NM_001042364, NM_001042365, NM_001320681, NM_001320682, NM_001320683, NM_001320684, NM_001320685, NM_001320686, NM_001320688, NM_001320689, NM_001320690, NM_001320691, NM_001352521, NM_001352522, NM_001352523, NM_001352524, NM_001352525, NM_001352526, NM_001352527, NM_001352528, NM_001352529, NM_001352530, NM_001352531, NM_001352532, NM_001352533, NM_001352534, NM_001352535, NM_001352536, NM_001352537, NM_001352538, NM_001352539, NM_001352540, NM_001352541, NM_001352542, NM_001352543, NM_001352545, NM_001352547, NM_001352548, NM_001352549, NM_001352550, NM_001352551, NM_001352552, NM_001352553, NM_001352554, NM_001352555, NM_015605

CCDS: CCDS73105, CCDS73106, CCDS73107, CCDS73108, CCDS73109, CCDS73110, CCDS73111, CCDS73114, CCDS73115, CCDS73116, CCDS81454, CCDS81456, CCDS86087

Canonical transcript exons

ENST00000374339 — 11 exons

Exon	Start	End
ENSE00002512165	46911428	46911501
ENSE00003465258	47000676	47002322
ENSE00003512451	46940623	46940717
ENSE00003548703	46984230	46984564
ENSE00003559122	46964986	46965137
ENSE00003562313	46943918	46944015
ENSE00003580116	46932377	46932533
ENSE00003629204	46967957	46968047
ENSE00003666118	46987340	46987555
ENSE00003673124	46946563	46946675
ENSE00003748210	46999912	46999974

Expression profiles

Bgee: expression breadth ubiquitous, 205 present calls, max score 90.60.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2068 / max 17.4796, expressed in 123 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
205848	0.2068	123

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pons	UBERON:0000988	90.60	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.82	gold quality
adrenal tissue	UBERON:0018303	84.09	gold quality
hindlimb stylopod muscle	UBERON:0004252	82.26	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.20	gold quality
right testis	UBERON:0004534	81.46	gold quality
left testis	UBERON:0004533	81.45	gold quality
testis	UBERON:0000473	80.86	gold quality
right adrenal gland	UBERON:0001233	79.32	gold quality
right adrenal gland cortex	UBERON:0035827	78.99	gold quality
heart left ventricle	UBERON:0002084	78.77	gold quality
right uterine tube	UBERON:0001302	78.60	gold quality
cerebellar cortex	UBERON:0002129	78.58	gold quality
left adrenal gland	UBERON:0001234	78.52	gold quality
cerebellar hemisphere	UBERON:0002245	78.47	gold quality
cardiac ventricle	UBERON:0002082	78.33	gold quality
prefrontal cortex	UBERON:0000451	78.03	gold quality
left adrenal gland cortex	UBERON:0035825	77.91	gold quality
apex of heart	UBERON:0002098	77.77	gold quality
adrenal gland	UBERON:0002369	77.62	gold quality
cerebellum	UBERON:0002037	77.58	gold quality
islet of Langerhans	UBERON:0000006	77.50	gold quality
right hemisphere of cerebellum	UBERON:0014890	77.39	gold quality
right atrium auricular region	UBERON:0006631	77.24	gold quality
body of pancreas	UBERON:0001150	76.80	gold quality
heart	UBERON:0000948	76.55	gold quality
adrenal cortex	UBERON:0001235	76.45	gold quality
pancreas	UBERON:0001264	75.60	gold quality
cardiac atrium	UBERON:0002081	75.43	gold quality
muscle of leg	UBERON:0001383	75.33	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.48

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

96 targeting PTPN20, 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-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646

Literature-anchored findings (GeneRIF, showing 2)

• identification of hPTPN20a as a novel and widely expressed phosphatase with a dynamic subcellular distribution that is targeted to sites of actin polymerization (PMID:15790311)
• Identification of PTPN20 as an innate immunity-related gene in gastric cancer with Helicobacter pylori infection. (PMID:37359510)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ptpn20	ENSDARG00000075459
mus_musculus	Ptpn20	ENSMUSG00000021940
rattus_norvegicus	Ptpn20	ENSRNOG00000020203

Paralogs (35): PTPRN (ENSG00000054356), PTPRU (ENSG00000060656), PTPN3 (ENSG00000070159), PTPN21 (ENSG00000070778), PTPN18 (ENSG00000072135), PTPN23 (ENSG00000076201), PTPRH (ENSG00000080031), PTPRC (ENSG00000081237), PTPN4 (ENSG00000088179), PTPRS (ENSG00000105426), PTPRZ1 (ENSG00000106278), PTPN5 (ENSG00000110786), PTPN6 (ENSG00000111679), PTPRB (ENSG00000127329), PTPN12 (ENSG00000127947), PTPRE (ENSG00000132334), PTPRA (ENSG00000132670), PTPN22 (ENSG00000134242), PTPRF (ENSG00000142949), PTPN7 (ENSG00000143851), PTPRG (ENSG00000144724), PTPRJ (ENSG00000149177), PTPRO (ENSG00000151490), PTPN14 (ENSG00000152104), PTPRK (ENSG00000152894), PTPRR (ENSG00000153233), PTPRD (ENSG00000153707), PTPRN2 (ENSG00000155093), PTPN13 (ENSG00000163629), PTPN9 (ENSG00000169410), PTPRM (ENSG00000173482), PTPN2 (ENSG00000175354), PTPN11 (ENSG00000179295), PTPRT (ENSG00000196090), PTPN1 (ENSG00000196396)

Protein

Protein identifiers

Tyrosine-protein phosphatase non-receptor type 20 — Q4JDL3 (reviewed: Q4JDL3)

All UniProt accessions (6): A0A0A0MSU6, Q4JDL3, D6RC68, D6RF36, Q4JDK3, Q5T1G4

UniProt curated annotations — full annotation on UniProt →

Function. Tyrosine-protein phosphatase targeted to sites of actin polymerization in response of varied extracellular stimuli. Has tyrosine phosphatase activity towards various tyrosyl phosphorylated substrates.

Subcellular location. Nucleus. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome.

Tissue specificity. Present in many cell lines (at protein level). Widely expressed.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the protein-tyrosine phosphatase family. Non-receptor class subfamily.

Isoforms (15)

UniProt ID	Names	Canonical?
Q4JDL3-1	1	yes
Q4JDL3-2	2, Variant 1
Q4JDL3-3	3, Variant 10
Q4JDL3-4	4, Variant 12
Q4JDL3-5	5, Variant 13
Q4JDL3-6	6, Variant 3
Q4JDL3-7	7, Variant 7
Q4JDL3-8	8, Variant 4
Q4JDL3-9	9, Variant 18
Q4JDL3-10	10, Variant 8
Q4JDL3-11	11, Variant 2
Q4JDL3-12	12, Variant 11
Q4JDL3-13	13, Variant 9
Q4JDL3-14	14, Variant 14
Q4JDL3-15	15, Variant 5

RefSeq proteins (53): NP_001035816, NP_001035817, NP_001035818, NP_001035819, NP_001035820, NP_001035821, NP_001035822, NP_001035823, NP_001035824, NP_001307610, NP_001307611, NP_001307612, NP_001307613, NP_001307614, NP_001307615, NP_001307617, NP_001307618, NP_001307619, NP_001307620, NP_001339450, NP_001339451, NP_001339452, NP_001339453, NP_001339454, NP_001339455, NP_001339456, NP_001339457, NP_001339458, NP_001339459, NP_001339460, NP_001339461, NP_001339462, NP_001339463, NP_001339464, NP_001339465, NP_001339466, NP_001339467, NP_001339468, NP_001339469, NP_001339470, NP_001339471, NP_001339472, NP_001339474, NP_001339476, NP_001339477, NP_001339478, NP_001339479, NP_001339480, NP_001339481, NP_001339482, NP_001339483, NP_001339484, NP_056420 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000242	PTP_cat	Domain
IPR000387	Tyr_Pase_dom	Domain
IPR003595	Tyr_Pase_cat	Domain
IPR016130	Tyr_Pase_AS	Active_site
IPR029021	Prot-tyrosine_phosphatase-like	Homologous_superfamily
IPR052074	NonRcpt_TyrProt_Phosphatase	Family

Pfam: PF00102

Catalyzed reactions (Rhea), 1 shown:

• O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate (RHEA:10684)

UniProt features (25 total): splice variant 13, binding site 3, modified residue 2, region of interest 2, compositionally biased region 2, chain 1, domain 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q4JDL3-F1	78.24	0.62

Functional residue map

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

Catalytic / active sites (1): 353 (phosphocysteine intermediate)

Ligand- & substrate-binding residues (3): 323; 353–359; 397

Post-translational modifications (2): 76, 120

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9008059	Interleukin-37 signaling

MSigDB gene sets: 85 (showing top): MORF_ITGA2, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, MORF_RAD51L3, GOCC_MICROTUBULE_ORGANIZING_CENTER, MORF_CTSB, GOCC_CENTROSOME, MORF_PRKCA, KIM_WT1_TARGETS_12HR_UP, MORF_ATF2, CAMPS_COLON_CANCER_COPY_NUMBER_DN, GOCC_CENTRIOLAR_SATELLITE, MORF_PTPRR, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS, GOMF_PHOSPHORIC_ESTER_HYDROLASE_ACTIVITY, GOMF_PROTEIN_TYROSINE_PHOSPHATASE_ACTIVITY

GO Biological Process (3): lymphangiogenesis (GO:0001946), protein dephosphorylation (GO:0006470), dephosphorylation (GO:0016311)

GO Molecular Function (3): phosphoprotein phosphatase activity (GO:0004721), protein tyrosine phosphatase activity (GO:0004725), hydrolase activity (GO:0016787)

GO Cellular Component (7): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), microtubule (GO:0005874), centriolar satellite (GO:0034451), nucleus (GO:0005634), centrosome (GO:0005813), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Interleukin-1 family signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
anatomical structure morphogenesis	1
lymph vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
dephosphorylation	1
protein modification process	1
phosphate-containing compound metabolic process	1
phosphatase activity	1
catalytic activity, acting on a protein	1
phosphoprotein phosphatase activity	1
catalytic activity	1
nuclear lumen	1
intracellular anatomical structure	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
centrosome	1
intracellular membrane-bounded organelle	1
centriole	1
microtubule organizing center	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

828 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTPN20	FRMPD2	Q68DX3	533
PTPN20	TCAF1	Q9Y4C2	532
PTPN20	FAM81A	Q8TBF8	531
PTPN20	EGF	P01133	503
PTPN20	ARHGEF5	Q12774	494
PTPN20	ARHGEF35	A5YM69	492
PTPN20	GPRIN2	O60269	490
PTPN20	LMBR1L	Q6UX01	472
PTPN20	A0A1B0GVM2	A0A1B0GVM2	458
PTPN20	TCAF2	A6NFQ2	458
PTPN20	FAM72A	Q5TYM5	456
PTPN20	TOR2A	Q5JU69	438
PTPN20	ARHGAP11A	Q6P4F7	435
PTPN20	GTF2I	P78347	435
PTPN20	CD8B2	A6NJW9	433

IntAct

6 interactions, top by confidence:

A	B	Type	Score
PTPN20	PTPN20	psi-mi:“MI:0915”(physical association)	0.470
PTPN20	PTPN20	psi-mi:“MI:2364”(proximity)	0.470
PTPN20	GAPDHS	psi-mi:“MI:0915”(physical association)	0.400
NP	KPNA6	psi-mi:“MI:0914”(association)	0.350
NP	TRIM66	psi-mi:“MI:0914”(association)	0.350

BioGRID (14): PTPN20B (Affinity Capture-MS), PTPN20B (Affinity Capture-MS), PTPN20B (Proximity Label-MS), GAPDHS (Affinity Capture-MS), PTPN20B (Affinity Capture-MS), PTPN20B (Two-hybrid), PTPN20B (Two-hybrid), PTPN20B (Two-hybrid), PTPN20B (Two-hybrid), PTPN20B (Two-hybrid), PTPN20B (Two-hybrid), PRH1 (Affinity Capture-MS), PTPN1 (Affinity Capture-MS), PTPN6 (Affinity Capture-MS)

ESM2 similar proteins: A1L1L3, B3NKK1, B4IMC3, B4NSS9, G5EC24, G5EGA9, G5EGU2, H2KZM6, H2KZW3, O08617, O55082, P04157, P06800, P08575, P18052, P18475, P28192, P29349, P29351, P34138, P34337, P34442, P35235, P41499, P42083, P42159, P81718, Q05209, Q06124, Q10656, Q15256, Q20402, Q22712, Q4JDL3, Q5I124, Q5I128, Q5I137, Q5I138, Q5I139, Q5I141

Diamond homologs: A0A6I8TCE0, A1L1L3, A2ALK8, A4IFW2, B0V2N1, B0X4T2, B1AUH1, B2GV87, B2RU80, B3DK56, B9EKR1, E9Q0N2, E9Q612, F1NWE3, G5EC24, G5EGJ9, H2KZM6, O02695, O08617, O13016, O35239, O55082, P06800, P16620, P17706, P18031, P18052, P18433, P20417, P23467, P23468, P23469, P23470, P23471, P26045, P28191, P29074, P29350, P29351, P29352

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

2799 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:46984280:A:C	S212R	0.998
10:46984282:T:A	S212R	0.998
10:46984282:T:G	S212R	0.998
10:46987382:T:A	W321R	0.998
10:46987382:T:C	W321R	0.998
10:46984245:T:A	V200D	0.997
10:46984364:T:A	W240R	0.997
10:46984364:T:C	W240R	0.997
10:46984539:G:C	R298P	0.997
10:46999951:C:A	R392S	0.997
10:46999952:G:C	R392P	0.997
10:46984277:G:C	A211P	0.996
10:46987478:T:C	C353R	0.995
10:46987480:C:G	C353W	0.995
10:46984278:C:A	A211D	0.994
10:46987384:G:C	W321C	0.994
10:46987384:G:T	W321C	0.994
10:46968025:T:A	N187K	0.993
10:46968025:T:G	N187K	0.993
10:46968028:A:C	R188S	0.993
10:46968028:A:T	R188S	0.993
10:46984326:C:A	A227D	0.993
10:46987488:G:A	G356D	0.993
10:46987497:G:C	R359P	0.993
10:46984276:T:A	N210K	0.992
10:46984276:T:G	N210K	0.992
10:46987481:A:C	S354R	0.992
10:46987483:T:A	S354R	0.992
10:46987483:T:G	S354R	0.992
10:46987488:G:T	G356V	0.991

dbSNP variants (sampled 300 via entrez): RS1000405237 (10:47000464 C>T), RS1000666132 (10:46999158 A>G), RS1000734035 (10:47000792 C>G,T), RS1001142130 (10:46998859 C>T), RS1001484054 (10:46992672 T>C), RS1001515072 (10:46992306 A>G), RS1002407911 (10:46997275 A>G), RS1002507401 (10:47002973 T>C), RS1002644758 (10:47003245 A>G), RS1002707368 (10:46995913 C>A,G), RS1002744147 (10:46997789 A>G), RS1003148372 (10:46995717 A>C,G,T), RS1004317494 (10:46997847 C>G), RS1004414145 (10:46998038 G>A,C,T), RS1004589918 (10:47003281 T>C,G)

Disease associations

OMIM: gene MIM:610630 | 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

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation	2
CGP 52608	affects binding, increases reaction	1
ICG 001	increases expression	1
abrine	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Zoledronic Acid	increases expression	1
Copper	affects cotreatment, decreases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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