PUDP

Summary

PUDP (pseudouridine 5’-phosphatase, HGNC:16818) is a protein-coding gene on chromosome Xp22.31, encoding Pseudouridine-5’-phosphatase (Q08623). Dephosphorylates pseudouridine 5’-phosphate, a potential intermediate in rRNA degradation.

This gene encodes a member of the haloacid dehalogenase-like (HAD) hydrolase superfamily. The encoded protein has no known biological function. This gene has a pseudogene on chromosome 1. Multiple alternatively spliced transcript variants encoding different isoforms have been identified.

Source: NCBI Gene 8226 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 96 total — 14 pathogenic
• MANE Select transcript: NM_012080

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16818
Approved symbol	PUDP
Name	pseudouridine 5’-phosphatase
Location	Xp22.31
Locus type	gene with protein product
Status	Approved
Aliases	DXF68S1E, GS1
Ensembl gene	ENSG00000130021
Ensembl biotype	protein_coding
OMIM	306480
Entrez	8226

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000381077, ENST00000412827, ENST00000424830, ENST00000438499, ENST00000486446, ENST00000498474, ENST00000655425, ENST00000870960, ENST00000934726, ENST00000962956

RefSeq mRNA: 4 — MANE Select: NM_012080 NM_001135565, NM_001178135, NM_001178136, NM_012080

CCDS: CCDS48075, CCDS48076, CCDS55366, CCDS55367

Canonical transcript exons

ENST00000381077 — 4 exons

Exon	Start	End
ENSE00000664666	7077220	7077449
ENSE00001166329	7048920	7050472
ENSE00003597223	7105620	7105838
ENSE00003902470	7148053	7148153

Expression profiles

Bgee: expression breadth ubiquitous, 273 present calls, max score 92.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.1506 / max 183.5226, expressed in 1781 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
198358	13.9432	1781
198354	0.1694	18
198353	0.0207	2
198355	0.0111	2
198356	0.0062	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	92.79	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.24	gold quality
mucosa of sigmoid colon	UBERON:0004993	91.76	gold quality
biceps brachii	UBERON:0001507	91.55	gold quality
secondary oocyte	CL:0000655	91.47	gold quality
colonic mucosa	UBERON:0000317	91.31	gold quality
deltoid	UBERON:0001476	90.81	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	90.65	gold quality
tibialis anterior	UBERON:0001385	90.59	gold quality
epithelium of bronchus	UBERON:0002031	90.58	gold quality
bronchial epithelial cell	CL:0002328	90.42	gold quality
quadriceps femoris	UBERON:0001377	90.32	gold quality
vastus lateralis	UBERON:0001379	90.32	gold quality
bronchus	UBERON:0002185	90.02	gold quality
skeletal muscle tissue	UBERON:0001134	90.00	gold quality
placenta	UBERON:0001987	89.91	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.86	gold quality
monocyte	CL:0000576	89.55	gold quality
muscle organ	UBERON:0001630	89.45	gold quality
mononuclear cell	CL:0000842	89.37	gold quality
gastrocnemius	UBERON:0001388	89.33	gold quality
muscle of leg	UBERON:0001383	89.11	gold quality
leukocyte	CL:0000738	89.05	gold quality
muscle tissue	UBERON:0002385	88.83	gold quality
oocyte	CL:0000023	88.74	gold quality
heart right ventricle	UBERON:0002080	88.47	gold quality
ileal mucosa	UBERON:0000331	88.25	gold quality
left ventricle myocardium	UBERON:0006566	87.48	gold quality
diaphragm	UBERON:0001103	87.12	silver quality
duodenum	UBERON:0002114	86.64	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.22

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

74 targeting PUDP, 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-4262	100.00	73.26	3931
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-8076	99.78	68.52	1170
HSA-MIR-3913-3P	99.74	66.53	938
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-4255	99.72	67.70	1541
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-4677-5P	99.70	70.09	1940

Literature-anchored findings (GeneRIF, showing 2)

• HDHD1 is a phosphatase specifically involved in dephosphorylation of a modified nucleotide present in RNA. (PMID:20722631)
• STS and PUDP Deletion Identified by Targeted Panel Sequencing with CNV Analysis in X-Linked Ichthyosis: A Case Report and Literature Review. (PMID:37895274)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	pudp	ENSDARG00000027826
mus_musculus	Pudp	ENSMUSG00000048875
rattus_norvegicus	Pudp	ENSRNOG00000025422
drosophila_melanogaster	Gs1l	FBGN0019982
drosophila_melanogaster	CG5556	FBGN0031332
drosophila_melanogaster	CG5561	FBGN0031333
drosophila_melanogaster	CG5565	FBGN0031335
drosophila_melanogaster	CG31924	FBGN0051924
caenorhabditis_elegans		WBGENE00020113

Protein

Protein identifiers

Pseudouridine-5’-phosphatase — Q08623 (reviewed: Q08623)

Alternative names: Haloacid dehalogenase-like hydrolase domain-containing protein 1, Haloacid dehalogenase-like hydrolase domain-containing protein 1A, Protein GS1, Pseudouridine-5’-monophosphatase

All UniProt accessions (2): Q08623, A0A590UJH7

UniProt curated annotations — full annotation on UniProt →

Function. Dephosphorylates pseudouridine 5’-phosphate, a potential intermediate in rRNA degradation. Pseudouridine is then excreted intact in urine.

Induction. Inhibited by low concentrations of calcium.

Similarity. Belongs to the HAD-like hydrolase superfamily. CbbY/CbbZ/Gph/YieH family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q08623-1	1	yes
Q08623-2	2
Q08623-3	3
Q08623-4	4

RefSeq proteins (4): NP_001129037, NP_001171606, NP_001171607, NP_036212* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006439	HAD-SF_hydro_IA	Family
IPR023198	PGP-like_dom2	Homologous_superfamily
IPR023214	HAD_sf	Homologous_superfamily
IPR036412	HAD-like_sf	Homologous_superfamily
IPR041492	HAD_2	Family
IPR045228	Gpp1/Gpp2-like	Family

Pfam: PF13419

Catalyzed reactions (Rhea), 1 shown:

• psi-UMP + H2O = pseudouridine + phosphate (RHEA:10944)

UniProt features (37 total): helix 14, strand 7, sequence conflict 4, splice variant 3, active site 2, turn 2, binding site 2, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
9M7M	X-RAY DIFFRACTION	1.26
9M7L	X-RAY DIFFRACTION	1.36
3L5K	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q08623-F1	97.54	0.97

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): 14 (nucleophile); 16 (proton donor)

Ligand- & substrate-binding residues (2): 14; 16

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-73614	Pyrimidine salvage

MSigDB gene sets: 94 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, MODULE_493, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GENTILE_UV_HIGH_DOSE_DN, KIM_GERMINAL_CENTER_T_HELPER_UP, DOUGLAS_BMI1_TARGETS_DN, TIEN_INTESTINE_PROBIOTICS_24HR_UP, GENTILE_UV_RESPONSE_CLUSTER_D7, YAGI_AML_WITH_11Q23_REARRANGED, SAMOLS_TARGETS_OF_KHSV_MIRNAS_DN

GO Biological Process (1): nucleotide metabolic process (GO:0009117)

GO Molecular Function (5): phosphatase activity (GO:0016791), metal ion binding (GO:0046872), pseudouridine 5’-phosphatase activity (GO:1990738), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (1): cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Nucleotide salvage	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nucleoside phosphate metabolic process	1
phosphoric ester hydrolase activity	1
cation binding	1
phosphatase activity	1
binding	1
catalytic activity	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2145 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PUDP	PNPLA4	P41247	858
PUDP	STS	P08842	842
PUDP	VCX3A	Q9NNX9	720
PUDP	VCX2	Q9H322	665
PUDP	VCX3B	Q9H321	600
PUDP	EIF2S3	P41091	594
PUDP	ASMTL	O95671	567
PUDP	PLCXD1	Q9NUJ7	523
PUDP	KDM6A	O15550	521
PUDP	NLGN4X	Q8N0W4	486
PUDP	CPPED1	Q9BRF8	461
PUDP	UBE3D	Q7Z6J8	450
PUDP	ARSD	P51689	448
PUDP	PRKX	P51817	445
PUDP	PLPP6	Q8IY26	445

IntAct

11 interactions, top by confidence:

A	B	Type	Score
PUDP	AIRIM	psi-mi:“MI:0915”(physical association)	0.560
PUDP	GLYCTK	psi-mi:“MI:0915”(physical association)	0.560
MAGEA4	PUDP	psi-mi:“MI:0915”(physical association)	0.560
PUDP	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
PUDP	MAGEA4	psi-mi:“MI:0915”(physical association)	0.000
AIRIM	PUDP	psi-mi:“MI:0915”(physical association)	0.000
GLYCTK	PUDP	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (62): HDHD1 (Affinity Capture-RNA), HDHD1 (Affinity Capture-RNA), CNDP2 (Co-fractionation), HDHD1 (Co-fractionation), HDHD1 (Co-fractionation), HDHD1 (Co-fractionation), HDHD1 (Co-fractionation), HDHD1 (Co-fractionation), NANP (Co-fractionation), QDPR (Co-fractionation), HDHD1 (Affinity Capture-MS), HDHD1 (Affinity Capture-MS), HDHD1 (Two-hybrid), MAGEA4 (Two-hybrid), GLYCTK (Two-hybrid)

ESM2 similar proteins: A0A1D6NER6, A1SY91, A6ZN46, A6ZRD1, C5DDS4, C5DXI0, C7GKE1, C8ZHD6, N1P3Y5, O14165, O42615, O59760, O94574, O94634, P0CT22, P10356, P25379, P25721, P31318, P31688, P32626, P32643, P33677, P34492, P36151, P38773, P38774, P38812, P40106, P41277, P53078, P53759, P53981, Q08623, Q08911, Q09893, Q12486, Q6C8V1, Q84MD8, Q86ZR7

Diamond homologs: F4JTE7, O14165, O59760, Q08623, Q15JF8, Q84MD8, Q86ZR7, Q8VZP1, Q94529, Q9D5U5, Q9X0Y1, Q9A5Z2, Q9ZVJ5, O33513, P35924, P54607, P95649, Q2RPW9, Q8UEY9, Q9L392, P44004, P77475, Q5M969, Q9CPT3, A0RKU8, A8FHS1, A9VQ75, B7HEG2, B7HWY7, B7IPS5, B7JFI8, B9J4R5, C1EZE2, C3LED0, C3P0C8, O06995, P32662, P58422, P65070, P77247

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
PUDP	“down-regulates quantity”	“pseudouridine 5’-phosphate(2-)”	“chemical modification”
PUDP	“down-regulates quantity”	water	“chemical modification”
PUDP	“up-regulates quantity”	pseudouridine	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	14
Likely pathogenic	0
Uncertain significance	47
Likely benign	10
Benign	2

Top pathogenic / likely-pathogenic (14)

Variant ID	HGVS	Classification
1341122	GRCh37/hg19 Xp22.31(chrX:6722953-7570280)x0	Pathogenic
2661880	GRCh37/hg19 Xp22.31(chrX:6968337-7894160)x0	Pathogenic
2685693	GRCh37/hg19 Xp22.31(chrX:6778999-8075687)x1	Pathogenic
3024648	GRCh37/hg19 Xp22.31(chrX:6515107-8123681)x1	Pathogenic
3391946	GRCh37/hg19 Xp22.31(chrX:6966446-7573818)x0	Pathogenic
3770225	GRCh37/hg19 Xp22.31(chrX:6640000-7760000)x0	Pathogenic
446317	GRCh37/hg19 Xp22.31(chrX:6962965-7745286)x0	Pathogenic
4820163	NC_000023.10:g.(6452559_6453559)_(8136659_8137559)del	Pathogenic
564760	GRCh37/hg19 Xp22.31(chrX:6542443-7951092)x0	Pathogenic
564761	GRCh37/hg19 Xp22.31(chrX:6577106-8041392)x0	Pathogenic
564766	GRCh37/hg19 Xp22.31(chrX:6759774-7766481)x1	Pathogenic
59233	GRCh38/hg38 Xp22.31(chrX:6832908-6906043)x1	Pathogenic
625642	GRCh37/hg19 Xp22.31(chrX:6696168-7396902)	Pathogenic
980837	GRCh37/hg19 Xp22.31(chrX:6715352-7806067)x0	Pathogenic

SpliceAI

1382 predictions. Top by Δscore:

Variant	Effect	Δscore
X:7077216:TTAC:T	donor_loss	1.0000
X:7077217:TACCT:T	donor_loss	1.0000
X:7077218:A:C	donor_loss	1.0000
X:7077219:C:CA	donor_loss	1.0000
X:7077219:CCTT:C	donor_gain	1.0000
X:7077447:CCC:C	acceptor_gain	1.0000
X:7077448:CC:C	acceptor_gain	1.0000
X:7077448:CCC:C	acceptor_gain	1.0000
X:7077449:CC:C	acceptor_gain	1.0000
X:7077450:C:CC	acceptor_gain	1.0000
X:7105592:AAC:A	donor_gain	1.0000
X:7105649:T:TA	donor_gain	1.0000
X:7105650:C:A	donor_gain	1.0000
X:7105834:AGTAT:A	acceptor_gain	1.0000
X:7105835:GTAT:G	acceptor_gain	1.0000
X:7105836:TAT:T	acceptor_gain	1.0000
X:7105837:AT:A	acceptor_gain	1.0000
X:7105838:TC:T	acceptor_loss	1.0000
X:7105839:C:CC	acceptor_gain	1.0000
X:7105839:CTG:C	acceptor_loss	1.0000
X:7105840:T:A	acceptor_loss	1.0000
X:7050473:C:CC	acceptor_gain	0.9900
X:7077218:A:AC	donor_gain	0.9900
X:7077219:C:CC	donor_gain	0.9900
X:7077445:CGCCC:C	acceptor_gain	0.9900
X:7077449:CCTGG:C	acceptor_loss	0.9900
X:7077450:C:CG	acceptor_loss	0.9900
X:7077450:C:T	acceptor_gain	0.9900
X:7077451:T:A	acceptor_loss	0.9900
X:7105614:CCGCA:C	donor_loss	0.9900

AlphaMissense

1503 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:7050455:A:C	D176E	0.998
X:7050455:A:T	D176E	0.998
X:7148067:T:A	D16V	0.997
X:7050457:C:G	D176H	0.996
X:7077256:A:C	C158W	0.996
X:7077283:C:A	K149N	0.996
X:7077283:C:G	K149N	0.996
X:7077361:C:A	K123N	0.996
X:7077361:C:G	K123N	0.996
X:7105835:G:A	T22I	0.996
X:7148064:C:T	G17E	0.996
X:7148068:C:G	D16H	0.996
X:7148073:T:A	D14V	0.996
X:7050456:T:A	D176V	0.995
X:7077285:T:C	K149E	0.995
X:7077285:T:G	K149Q	0.995
X:7077388:G:C	S114R	0.995
X:7077388:G:T	S114R	0.995
X:7077390:T:G	S114R	0.995
X:7148066:G:C	D16E	0.995
X:7148066:G:T	D16E	0.995
X:7050456:T:G	D176A	0.994
X:7050459:T:A	E175V	0.994
X:7077284:T:G	K149T	0.994
X:7105749:C:G	G51R	0.994
X:7148072:G:C	D14E	0.994
X:7148072:G:T	D14E	0.994
X:7050408:A:T	V192D	0.993
X:7050445:C:A	G180W	0.993
X:7050456:T:C	D176G	0.993

dbSNP variants (sampled 300 via entrez): RS1000001688 (X:6870976 T>A), RS1000002216 (X:6884782 G>T), RS1000016422 (X:6727161 A>C), RS1000017707 (X:7039530 G>A), RS1000018923 (X:7127530 G>C), RS1000053282 (X:6789057 A>G), RS1000075486 (X:6797259 C>T), RS1000086476 (X:7073150 G>A), RS1000095480 (X:6957579 A>C), RS1000097809 (X:6846819 G>T), RS1000108865 (X:7030982 C>T), RS1000111598 (X:6853966 G>T), RS1000119346 (X:6881709 A>G), RS1000128133 (X:6788763 A>G), RS1000150565 (X:6715595 A>G)

Disease associations

OMIM: gene MIM:306480 | disease phenotypes: MIM:308100

GenCC curated gene-disease

Mondo (1): recessive X-linked ichthyosis (MONDO:0010622)

Orphanet (1): Recessive X-linked ichthyosis (Orphanet:461)

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

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

Chemical	Actions (top 5)	PubMed papers
Nickel	increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cyclosporine	decreases expression	2
GSK-J4	decreases expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
benzo(e)pyrene	decreases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
2-palmitoylglycerol	increases expression	1
monomethylarsonous acid	increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
abrine	decreases expression	1
bisphenol AF	increases expression	1
Temozolomide	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Air Pollutants	decreases expression, increases abundance	1
Dactinomycin	affects cotreatment, increases secretion	1
Ivermectin	decreases expression	1
Methapyrilene	decreases methylation	1
Methotrexate	affects response to substance	1
Methyl Methanesulfonate	decreases expression	1
Thiram	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	affects expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00074685	Not specified	COMPLETED	National Registry for Ichthyosis and Related Disorders