PHOSPHO2

Summary

PHOSPHO2 (phosphatase, orphan 2, HGNC:28316) is a protein-coding gene on chromosome 2q31.1, encoding Pyridoxal phosphate phosphatase PHOSPHO2 (Q8TCD6). Phosphatase that has high activity toward pyridoxal 5’-phosphate (PLP).

Predicted to enable phosphatase activity.

Source: NCBI Gene 493911 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 32 total
• MANE Select transcript: NM_001008489

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28316
Approved symbol	PHOSPHO2
Name	phosphatase, orphan 2
Location	2q31.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC22679
Ensembl gene	ENSG00000144362
Ensembl biotype	protein_coding
Entrez	493911

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 33 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000359744, ENST00000438710, ENST00000438838, ENST00000449906, ENST00000476919, ENST00000616481, ENST00000616524, ENST00000617738, ENST00000857416, ENST00000857417, ENST00000857418, ENST00000857419, ENST00000857420, ENST00000857421, ENST00000857422, ENST00000857423, ENST00000857424, ENST00000931227, ENST00000931228, ENST00000931229, ENST00000931230, ENST00000931231, ENST00000931232, ENST00000931233, ENST00000931234, ENST00000931235, ENST00000931236, ENST00000931237, ENST00000931238, ENST00000931239, ENST00000931240, ENST00000961207, ENST00000961208, ENST00000961209

RefSeq mRNA: 5 — MANE Select: NM_001008489 NM_001008489, NM_001199285, NM_001199286, NM_001199287, NM_001199288

CCDS: CCDS33319

Canonical transcript exons

ENST00000359744 — 4 exons

Exon	Start	End
ENSE00001413182	169700946	169701708
ENSE00001466648	169694469	169694622
ENSE00003515401	169697361	169697531
ENSE00003520671	169695215	169695247

Expression profiles

Bgee: expression breadth ubiquitous, 237 present calls, max score 96.30.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0250 / max 4.5835, expressed in 15 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
23564	5.7217	1471
23566	0.0250	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	96.30	gold quality
oocyte	CL:0000023	96.21	gold quality
sperm	CL:0000019	94.25	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.33	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.95	gold quality
corpus epididymis	UBERON:0004359	86.54	gold quality
caput epididymis	UBERON:0004358	86.45	gold quality
tibia	UBERON:0000979	85.69	gold quality
epithelial cell of pancreas	CL:0000083	84.81	gold quality
left testis	UBERON:0004533	84.42	gold quality
right testis	UBERON:0004534	84.06	gold quality
testis	UBERON:0000473	83.61	gold quality
bronchial epithelial cell	CL:0002328	82.38	gold quality
cauda epididymis	UBERON:0004360	82.18	gold quality
bronchus	UBERON:0002185	81.39	gold quality
calcaneal tendon	UBERON:0003701	80.91	gold quality
germinal epithelium of ovary	UBERON:0001304	80.43	gold quality
rectum	UBERON:0001052	80.18	gold quality
epithelium of mammary gland	UBERON:0003244	80.11	gold quality
mammary duct	UBERON:0001765	80.03	gold quality
thoracic mammary gland	UBERON:0005200	79.68	gold quality
mammary gland	UBERON:0001911	79.57	gold quality
mucosa of paranasal sinus	UBERON:0005030	79.20	gold quality
duodenum	UBERON:0002114	79.19	gold quality
islet of Langerhans	UBERON:0000006	78.82	gold quality
right uterine tube	UBERON:0001302	78.77	gold quality
prostate gland	UBERON:0002367	78.76	gold quality
thyroid gland	UBERON:0002046	78.63	gold quality
adipose tissue	UBERON:0001013	78.48	gold quality
muscle layer of sigmoid colon	UBERON:0035805	78.41	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.44

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• Models of PHOSPHO2 and PHOSPHO1 suggest subtle differences in the charge distributions around the putative substrate entry site and in the location of potential H-bond donors. (PMID:16054448)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	phospho2	ENSDARG00000102202
mus_musculus	Phospho2	ENSMUSG00000027088
rattus_norvegicus	Phospho2	ENSRNOG00000007979
drosophila_melanogaster	CG14212	FBGN0031045
drosophila_melanogaster	CG12237	FBGN0031048

Paralogs (1): PHOSPHO1 (ENSG00000173868)

Protein

Protein identifiers

Pyridoxal phosphate phosphatase PHOSPHO2 — Q8TCD6 (reviewed: Q8TCD6)

All UniProt accessions (4): Q8TCD6, C9J4G2, C9JD35, C9JZQ7

UniProt curated annotations — full annotation on UniProt →

Function. Phosphatase that has high activity toward pyridoxal 5’-phosphate (PLP). Also active at much lower level toward pyrophosphate, phosphoethanolamine (PEA), phosphocholine (PCho), phospho-l-tyrosine, fructose-6-phosphate, p-nitrophenyl phosphate, and h-glycerophosphate.

Similarity. Belongs to the HAD-like hydrolase superfamily. PHOSPHO family.

RefSeq proteins (5): NP_001008489, NP_001186214, NP_001186215, NP_001186216, NP_001186217 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006384	HAD_hydro_PyrdxlP_Pase-like	Family
IPR016965	Pase_PHOSPHO-typ	Family
IPR023214	HAD_sf	Homologous_superfamily
IPR036412	HAD-like_sf	Homologous_superfamily

Pfam: PF06888

Catalyzed reactions (Rhea), 1 shown:

• pyridoxal 5’-phosphate + H2O = pyridoxal + phosphate (RHEA:20533)

UniProt features (9 total): binding site 5, active site 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TCD6-F1	96.04	0.94

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 (2): 8 (nucleophile); 10 (proton donor)

Ligand- & substrate-binding residues (5): 8; 10; 19; 99; 179

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 52 (showing top): GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS, GOMF_PHOSPHORIC_ESTER_HYDROLASE_ACTIVITY, JOHNSTONE_PARVB_TARGETS_3_DN, WAKABAYASHI_ADIPOGENESIS_PPARG_RXRA_BOUND_8D, FORTSCHEGGER_PHF8_TARGETS_DN, GOMF_PHOSPHATASE_ACTIVITY, WNT_UP.V1_DN, FOXJ2_TARGET_GENES, FOXN3_TARGET_GENES, ZNF711_TARGET_GENES, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_2, GSE14769_UNSTIM_VS_120MIN_LPS_BMDM_UP, GSE14769_UNSTIM_VS_240MIN_LPS_BMDM_DN, GSE15930_STIM_VS_STIM_AND_IFNAB_48H_CD8_T_CELL_DN, GSE17721_CPG_VS_GARDIQUIMOD_24H_BMDC_DN

GO Biological Process (0):

GO Molecular Function (5): phosphatase activity (GO:0016791), pyridoxal phosphatase activity (GO:0033883), metal ion binding (GO:0046872), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phosphoric ester hydrolase activity	1
phosphatase activity	1
cation binding	1
binding	1
catalytic activity	1

Protein interactions and networks

STRING

268 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PHOSPHO2	KLHL23	Q8NBE8	608
PHOSPHO2	A0A0A6YYL6	A0A0A6YYL6	605
PHOSPHO2	A6NDT3	A6NDT3	579
PHOSPHO2	C18orf32	Q8TCD1	446
PHOSPHO2	GMNC	A6NCL1	387
PHOSPHO2	ZNF417	Q8TAU3	375
PHOSPHO2	RPL17	P18621	375
PHOSPHO2	IWS1	Q96ST2	359
PHOSPHO2	RBMXL1	Q96E39	358
PHOSPHO2	PAPSS1	O43252	338
PHOSPHO2	OSTN	P61366	337
PHOSPHO2	IAH1	Q2TAA2	334
PHOSPHO2	ARHGAP8	P85298	321
PHOSPHO2	PNPO	Q9NVS9	306
PHOSPHO2	RETSAT	Q6NUM9	301

IntAct

41 interactions, top by confidence:

A	B	Type	Score
NAB2	PHOSPHO2	psi-mi:“MI:0915”(physical association)	0.720
GKAP1	PHOSPHO2	psi-mi:“MI:0915”(physical association)	0.560
PHOSPHO2	WASHC3	psi-mi:“MI:0915”(physical association)	0.560
FLNA	PHOSPHO2	psi-mi:“MI:0915”(physical association)	0.560
PHOSPHO2	TSEN15	psi-mi:“MI:0915”(physical association)	0.560
ATP5PF	PHOSPHO2	psi-mi:“MI:0915”(physical association)	0.560
PHOSPHO2	C1QTNF2	psi-mi:“MI:0915”(physical association)	0.560
PHOSPHO2	VHL	psi-mi:“MI:0915”(physical association)	0.560
PHOSPHO2	JPH3	psi-mi:“MI:0915”(physical association)	0.560
PHOSPHO2	SIGLEC5	psi-mi:“MI:0914”(association)	0.530
PHOSPHO2	SPARC	psi-mi:“MI:0915”(physical association)	0.400
PHOSPHO2	FLNA	psi-mi:“MI:0915”(physical association)	0.000
PHOSPHO2	NAB2	psi-mi:“MI:0915”(physical association)	0.000
PHOSPHO2	GKAP1	psi-mi:“MI:0915”(physical association)	0.000
PHOSPHO2	WASHC3	psi-mi:“MI:0915”(physical association)	0.000
PHOSPHO2	ATP5PF	psi-mi:“MI:0915”(physical association)	0.000
PHOSPHO2	TSEN15	psi-mi:“MI:0915”(physical association)	0.000
PHOSPHO2	C1QTNF2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (15): PHOSPHO2 (Two-hybrid), DNTTIP1 (Affinity Capture-MS), SIGLEC5 (Affinity Capture-MS), CPNE4 (Affinity Capture-MS), PHOSPHO2 (Two-hybrid), C1QTNF2 (Two-hybrid), ATP5J (Two-hybrid), GKAP1 (Two-hybrid), NAB2 (Two-hybrid), FLNA (Two-hybrid), TSEN15 (Two-hybrid), PHOSPHO2 (Proximity Label-MS), PHOSPHO2 (Affinity Capture-RNA), DNTTIP1 (Affinity Capture-MS), SIGLEC5 (Affinity Capture-MS)

ESM2 similar proteins: A1TZ36, A8Y461, A9RBS1, B3M173, B3P2A7, B4GFE6, B4I3X6, B4JSP3, B4KCL9, B4PV71, B4QW91, B5X2D1, C3XR70, C5DDS4, C7Z9X4, D2UYP1, O80738, Q00IB6, Q08B22, Q0J7N5, Q0WUI9, Q21012, Q28C69, Q296B0, Q2KI06, Q2SKZ0, Q2TAG6, Q3TZM9, Q569R5, Q66HC4, Q66KD6, Q6C8V1, Q6DE00, Q6GMI7, Q6NWX7, Q6P312, Q7Q9C0, Q7ZW24, Q7ZWS2, Q84MD8

Diamond homologs: O73884, Q2KI06, Q66HC4, Q66KD6, Q67YC0, Q6DBV4, Q8R2H9, Q8TCD6, Q8TCT1, Q9D9M5, Q9FZ62, Q9SU92

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

837 predictions. Top by Δscore:

Variant	Effect	Δscore
2:169694627:G:GG	donor_gain	1.0000
2:169694518:GGCTT:G	donor_gain	0.9800
2:169694519:GCTT:G	donor_gain	0.9800
2:169694519:GCTTG:G	donor_gain	0.9800
2:169694523:G:GG	donor_gain	0.9800
2:169694799:TG:T	donor_gain	0.9800
2:169694800:GG:G	donor_gain	0.9800
2:169701122:GTCTT:G	donor_gain	0.9800
2:169701123:TCTTT:T	donor_gain	0.9800
2:169694623:GTCA:G	donor_gain	0.9700
2:169694626:A:AG	donor_gain	0.9700
2:169695244:GCTG:G	donor_gain	0.9700
2:169695247:GGTA:G	donor_loss	0.9700
2:169695248:G:GG	donor_gain	0.9700
2:169695248:GT:G	donor_loss	0.9700
2:169695249:TAA:T	donor_loss	0.9700
2:169695249:TAAG:T	donor_loss	0.9700
2:169695250:A:AG	donor_loss	0.9700
2:169695250:AA:A	donor_loss	0.9700
2:169698246:T:A	donor_gain	0.9700
2:169701126:T:G	donor_gain	0.9700
2:169701126:T:TG	donor_gain	0.9700
2:169694634:GCCC:G	donor_gain	0.9600
2:169695210:TTTA:T	acceptor_loss	0.9600
2:169695213:A:G	acceptor_loss	0.9600
2:169695214:G:A	acceptor_loss	0.9600
2:169695251:AG:A	donor_loss	0.9600
2:169694803:GT:G	donor_gain	0.9500
2:169695211:TTA:T	acceptor_loss	0.9500
2:169695212:TAG:T	acceptor_loss	0.9500

AlphaMissense

1621 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:169701429:A:T	K153I	0.997
2:169701430:A:C	K153N	0.990
2:169701430:A:T	K153N	0.990
2:169700995:C:A	D8E	0.989
2:169700995:C:G	D8E	0.989
2:169700994:A:T	D8V	0.986
2:169701023:A:C	S18R	0.982
2:169701025:T:A	S18R	0.982
2:169701025:T:G	S18R	0.982
2:169701429:A:C	K153T	0.982
2:169701567:G:C	R199P	0.982
2:169700994:A:C	D8A	0.979
2:169701644:T:A	W225R	0.978
2:169701644:T:C	W225R	0.978
2:169701520:T:A	D183E	0.977
2:169701520:T:G	D183E	0.977
2:169701000:A:T	D10V	0.975
2:169701001:C:A	D10E	0.974
2:169701001:C:G	D10E	0.974
2:169701268:T:A	D99E	0.974
2:169701268:T:G	D99E	0.974
2:169701507:A:T	D179V	0.972
2:169701267:A:T	D99V	0.971
2:169701274:T:A	N101K	0.971
2:169701274:T:G	N101K	0.971
2:169701421:T:A	N150K	0.971
2:169701421:T:G	N150K	0.971
2:169701425:T:A	C152S	0.971
2:169701426:G:C	C152S	0.971
2:169701518:G:C	D183H	0.971

dbSNP variants (sampled 300 via entrez): RS1000145909 (2:169696623 A>G), RS1000178995 (2:169696172 C>T), RS1000426311 (2:169694624 T>C), RS1000864554 (2:169700789 A>C), RS1000895554 (2:169700317 G>C), RS1001032342 (2:169701844 G>A), RS1001465328 (2:169695727 A>G), RS1001816246 (2:169697783 A>G), RS1001847137 (2:169697453 G>A), RS1002521178 (2:169700912 G>A), RS1002726862 (2:169694529 G>C,T), RS1003386907 (2:169699053 G>A), RS1003528307 (2:169699264 T>G), RS1004217345 (2:169697305 C>T), RS1004265746 (2:169695512 C>A)

Disease associations

OMIM: gene `` | 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
GCST005184_8	Common carotid intima-media thickness in HIV infection	5.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	decreases expression, affects cotreatment	3
Dexamethasone	increases expression, affects cotreatment	2
Nickel	decreases expression	2
Cyclosporine	decreases expression	2
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases expression	1
potassium chromate(VI)	increases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	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
(+)-JQ1 compound	decreases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Acetaminophen	increases expression	1
Cisplatin	decreases expression	1
Coumestrol	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Quercetin	affects expression	1
Dihydrotestosterone	increases expression	1
Urethane	decreases expression	1
Vanadates	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Aflatoxin B1	decreases methylation	1
Copper Sulfate	decreases expression	1
Magnetite Nanoparticles	increases methylation	1

Clinical trials (associated diseases)

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