PSTK

Summary

PSTK (phosphoseryl-tRNA kinase, HGNC:28578) is a protein-coding gene on chromosome 10q26.13, encoding L-seryl-tRNA(Sec) kinase (Q8IV42). Specifically phosphorylates seryl-tRNA(Sec) to O-phosphoseryl-tRNA(Sec), an activated intermediate for selenocysteine biosynthesis. It is a selective cancer dependency (DepMap: 55.0% of cell lines).

Predicted to enable kinase activity and tRNA binding activity. Predicted to be involved in translation. Predicted to act upstream of or within selenocysteine incorporation.

Source: NCBI Gene 118672 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 40 total
• Cancer dependency (DepMap): dependent in 55.0% of screened cell lines
• MANE Select transcript: NM_001363531

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28578
Approved symbol	PSTK
Name	phosphoseryl-tRNA kinase
Location	10q26.13
Locus type	gene with protein product
Status	Approved
Aliases	MGC35392
Ensembl gene	ENSG00000179988
Ensembl biotype	protein_coding
OMIM	611310
Entrez	118672

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding_CDS_not_defined, 3 protein_coding, 1 retained_intron

ENST00000368887, ENST00000405485, ENST00000406217, ENST00000465232, ENST00000483455, ENST00000483755, ENST00000493461, ENST00000496079, ENST00000497219

RefSeq mRNA: 2 — MANE Select: NM_001363531 NM_001363531, NM_153336

CCDS: CCDS7633, CCDS86153

Canonical transcript exons

ENST00000406217 — 6 exons

Exon	Start	End
ENSE00001253355	122982733	122983024
ENSE00001674773	122980401	122980695
ENSE00003494362	122983272	122983470
ENSE00003566173	122986869	122986962
ENSE00003587065	122986300	122986375
ENSE00003662770	122990174	122990390

Expression profiles

Bgee: expression breadth ubiquitous, 199 present calls, max score 86.67.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.7260 / max 68.3181, expressed in 1711 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
107471	3.9798	1580
107470	3.2588	1054
107472	0.4874	255

Top tissues by expression

246 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	86.67	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.31	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	83.76	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.69	gold quality
prefrontal cortex	UBERON:0000451	82.84	gold quality
right frontal lobe	UBERON:0002810	81.47	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	81.27	gold quality
anterior cingulate cortex	UBERON:0009835	81.25	gold quality
caudate nucleus	UBERON:0001873	80.32	gold quality
spinal cord	UBERON:0002240	80.11	gold quality
cortical plate	UBERON:0005343	79.67	gold quality
hypothalamus	UBERON:0001898	79.53	gold quality
amygdala	UBERON:0001876	79.43	gold quality
putamen	UBERON:0001874	79.40	gold quality
neocortex	UBERON:0001950	79.36	gold quality
nucleus accumbens	UBERON:0001882	79.17	gold quality
right lobe of liver	UBERON:0001114	79.11	gold quality
frontal cortex	UBERON:0001870	79.05	gold quality
body of pancreas	UBERON:0001150	78.46	gold quality
cerebral cortex	UBERON:0000956	78.21	gold quality
adenohypophysis	UBERON:0002196	78.06	gold quality
pituitary gland	UBERON:0000007	78.03	gold quality
cerebellar hemisphere	UBERON:0002245	77.93	gold quality
right hemisphere of cerebellum	UBERON:0014890	77.92	gold quality
gastrocnemius	UBERON:0001388	77.83	gold quality
cerebellar cortex	UBERON:0002129	77.76	gold quality
right adrenal gland cortex	UBERON:0035827	77.64	gold quality
forebrain	UBERON:0001890	77.58	gold quality
ganglionic eminence	UBERON:0004023	77.32	gold quality
right adrenal gland	UBERON:0001233	77.27	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-6142	no	51.79
E-ANND-3	no	4.75

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting PSTK, 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-590-3P	99.96	74.34	6478
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-489-3P	99.80	66.46	839
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-148A-5P	99.30	68.27	1141
HSA-MIR-16-2-3P	99.29	70.60	1954
HSA-MIR-195-3P	99.29	70.61	1954
HSA-MIR-5584-3P	99.23	68.79	1351
HSA-MIR-502-5P	98.77	66.51	906
HSA-MIR-6728-3P	98.63	67.63	1534
HSA-MIR-22-5P	97.67	68.92	1355
HSA-MIR-4774-5P	95.92	68.27	827

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 55.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• Same but different - Molecular comparison of human KTI12 and PSTK. (PMID:33417976)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
		ENSDARG00000101800
danio_rerio		ENSDARG00000115015
mus_musculus	Pstk	ENSMUSG00000063179
rattus_norvegicus	Pstk	ENSRNOG00000020605
drosophila_melanogaster	Pstk	FBGN0031041
caenorhabditis_elegans		WBGENE00013041

Protein

Protein identifiers

L-seryl-tRNA(Sec) kinase — Q8IV42 (reviewed: Q8IV42)

Alternative names: O-phosphoseryl-tRNA(Sec) kinase

All UniProt accessions (2): Q8IV42, H7BYY4

UniProt curated annotations — full annotation on UniProt →

Function. Specifically phosphorylates seryl-tRNA(Sec) to O-phosphoseryl-tRNA(Sec), an activated intermediate for selenocysteine biosynthesis. No activity with other tRNAs has been detected.

Pathway. Aminoacyl-tRNA biosynthesis; selenocysteinyl-tRNA(Sec) biosynthesis; selenocysteinyl-tRNA(Sec) from L-seryl-tRNA(Sec) (archaeal/eukaryal route): step 1/2.

Similarity. Belongs to the L-seryl-tRNA(Sec) kinase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IV42-1	1	yes
Q8IV42-2	2

RefSeq proteins (2): NP_001350460, NP_699167 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013641	KTI12/PSTK	Family
IPR020028	L-seryl-tRNA_Sec_kinase_euk	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR052648	Ser-tRNA(Sec)_kinase	Family

Pfam: PF08433

Catalyzed reactions (Rhea), 1 shown:

• L-seryl-tRNA(Sec) + ATP = O-phospho-L-seryl-tRNA(Sec) + ADP (RHEA:25037)

UniProt features (4 total): chain 1, binding site 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IV42-F1	76.96	0.47

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 (1): 25–32

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-2408557	Selenocysteine synthesis

MSigDB gene sets: 116 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_TRANSLATION, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, KEGG_AMINOACYL_TRNA_BIOSYNTHESIS, GOMF_TRNA_BINDING, GOMF_KINASE_ACTIVITY, GOMF_ADENYL_NUCLEOTIDE_BINDING, GOMF_TRANSFERASE_ACTIVITY_TRANSFERRING_PHOSPHORUS_CONTAINING_GROUPS, GOMF_CATALYTIC_ACTIVITY_ACTING_ON_RNA, GOMF_CATALYTIC_ACTIVITY_ACTING_ON_A_TRNA, REACTOME_SELENOAMINO_ACID_METABOLISM, GSE14415_INDUCED_TREG_VS_FOXP3_KO_INDUCED_TREG_DN, GSE14415_INDUCED_TREG_VS_TCONV_DN, ALKBH3_TARGET_GENES, CEBPZ_TARGET_GENES

GO Biological Process (2): translation (GO:0006412), selenocysteine incorporation (GO:0001514)

GO Molecular Function (6): tRNA binding (GO:0000049), ATP binding (GO:0005524), kinase activity (GO:0016301), L-seryl-tRNA(Sec) kinase activity (GO:0043915), nucleotide binding (GO:0000166), transferase activity (GO:0016740)

GO Cellular Component (0):

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Selenoamino acid metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
translational readthrough	1
RNA binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
transferase activity, transferring phosphorus-containing groups	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a tRNA	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
catalytic activity	1

Protein interactions and networks

STRING

360 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PSTK	EEFSEC	P57772	993
PSTK	SEPSECS	Q9HD40	993
PSTK	SARS1	P49591	990
PSTK	M0R2C6	M0R2C6	990
PSTK	SARS2	Q9NP81	990
PSTK	TRNAU1AP	Q9NX07	935
PSTK	SEPHS2	Q99611	916
PSTK	SECISBP2	Q96T21	886
PSTK	SEPHS1	P49903	807
PSTK	SCLY	Q96I15	711
PSTK	KTI12	Q96EK9	687
PSTK	SELENOK	Q9Y6D0	630
PSTK	SELENOP	P49908	611
PSTK	SELENOH	Q8IZQ5	551
PSTK	SELENOT	P62341	543

IntAct

0 interactions, top by confidence:

BioGRID (9): PSTK (Negative Genetic), PSTK (Negative Genetic), PSTK (Negative Genetic), PSTK (Two-hybrid), NAA10 (Affinity Capture-MS), SPIN3 (Affinity Capture-MS), TXLNG (Affinity Capture-MS), TXLNG (Affinity Capture-Western), PSTK (Affinity Capture-RNA)

ESM2 similar proteins: A2CI34, A2CI35, O14920, O15111, O18412, O43149, O88351, O93307, P29597, P52333, Q09178, Q13049, Q20CR4, Q28DZ1, Q4G3H4, Q4TVR5, Q4VSN1, Q4VSN2, Q4VSN3, Q4VSN4, Q4VSN5, Q5RBH9, Q5SSH7, Q5U464, Q5ZJB4, Q60680, Q62137, Q63272, Q67E00, Q67E01, Q6GM53, Q6XUX0, Q6XUX1, Q6XUX2, Q6XUX3, Q6ZWQ0, Q8BMQ2, Q8BP74, Q8BUI3, Q8CH72

Diamond homologs: P41476, Q58933, Q6LX62, Q8BP74, Q8IV42, Q8TUS5, Q9YCR6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1545 predictions. Top by Δscore:

Variant	Effect	Δscore
10:122980705:G:GT	donor_gain	1.0000
10:122980709:G:T	donor_gain	1.0000
10:122982850:G:GT	donor_gain	1.0000
10:122982850:G:T	donor_gain	1.0000
10:122990168:TTTTA:T	acceptor_loss	1.0000
10:122990169:TTTA:T	acceptor_loss	1.0000
10:122990170:TTAG:T	acceptor_loss	1.0000
10:122990171:TA:T	acceptor_loss	1.0000
10:122990172:A:AG	acceptor_gain	1.0000
10:122990172:A:C	acceptor_loss	1.0000
10:122990173:G:GG	acceptor_gain	1.0000
10:122990173:GAT:G	acceptor_gain	1.0000
10:122995988:CATTA:C	donor_loss	1.0000
10:122995992:ACC:A	donor_loss	1.0000
10:122995993:CC:C	donor_loss	1.0000
10:122996172:TCCAG:T	acceptor_gain	1.0000
10:122996173:CCAG:C	acceptor_gain	1.0000
10:122996173:CCAGC:C	acceptor_gain	1.0000
10:122996174:CAG:C	acceptor_gain	1.0000
10:122996174:CAGC:C	acceptor_gain	1.0000
10:122996175:AG:A	acceptor_gain	1.0000
10:122996177:C:CC	acceptor_gain	1.0000
10:122996179:A:C	acceptor_gain	1.0000
10:122996184:C:CT	acceptor_gain	1.0000
10:122996185:A:T	acceptor_gain	1.0000
10:122996188:G:C	acceptor_gain	1.0000
10:122996192:C:CT	acceptor_gain	1.0000
10:122996192:C:T	acceptor_gain	1.0000
10:122980568:G:GT	donor_gain	0.9900
10:122980569:A:T	donor_gain	0.9900

AlphaMissense

2358 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:122980571:A:T	K31I	0.995
10:122983283:T:C	F174L	0.990
10:122983285:T:A	F174L	0.990
10:122983285:T:G	F174L	0.990
10:122982975:T:A	N153K	0.987
10:122982975:T:G	N153K	0.987
10:122982971:A:T	D152V	0.986
10:122982996:A:C	R160S	0.985
10:122982996:A:T	R160S	0.985
10:122982993:G:A	M159I	0.984
10:122982993:G:C	M159I	0.984
10:122982993:G:T	M159I	0.984
10:122982995:G:C	R160T	0.984
10:122983019:G:C	R168P	0.983
10:122983418:T:A	W219R	0.982
10:122983418:T:C	W219R	0.982
10:122983016:C:A	A167D	0.980
10:122980570:A:C	K31Q	0.978
10:122983420:G:C	W219C	0.978
10:122983420:G:T	W219C	0.978
10:122982970:G:C	D152H	0.975
10:122980572:A:C	K31N	0.972
10:122980572:A:T	K31N	0.972
10:122982972:C:A	D152E	0.972
10:122982972:C:G	D152E	0.972
10:122983430:A:C	S223R	0.972
10:122983432:C:A	S223R	0.972
10:122983432:C:G	S223R	0.972
10:122982971:A:C	D152A	0.969
10:122982988:A:C	S158R	0.969

dbSNP variants (sampled 300 via entrez): RS1000307424 (10:122989596 G>A), RS1000449418 (10:122978559 AAGG>A), RS1000575232 (10:122985671 G>T), RS1001022737 (10:122987152 A>T), RS1001300456 (10:122990343 T>A,C), RS1001650436 (10:122984191 A>G), RS1001773684 (10:122990661 G>A), RS1001897447 (10:122978550 G>C), RS1001909441 (10:122978978 A>G), RS1002022144 (10:122978644 T>C), RS1002026248 (10:122985513 G>A,T), RS1002080457 (10:122985215 G>A), RS1002244131 (10:122985776 A>C), RS1002533053 (10:122986111 C>T), RS1002782064 (10:122989344 C>G,T)

Disease associations

OMIM: gene MIM:611310 | 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
GCST008502_11	Low susceptibility to hepatitis C infection	3.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010101	decreased susceptibility to hepatitis C infection

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	6
trichostatin A	affects cotreatment, decreases expression	3
sodium arsenite	decreases expression, increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
dicrotophos	decreases expression	1
pirinixic acid	increases activity, affects binding, decreases expression	1
arsenite	increases reaction, affects binding	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
entinostat	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
belinostat	decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	decreases response to substance	1
Benzo(a)pyrene	affects methylation	1
Estradiol	affects expression	1
Methyl Methanesulfonate	increases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Tretinoin	decreases expression	1
Tunicamycin	increases expression	1
Thapsigargin	increases expression	1

Clinical trials (associated diseases)

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