PYURF

Summary

PYURF (PIGY upstream open reading frame, HGNC:44317) is a protein-coding gene on chromosome 4q22.1, encoding Protein preY, mitochondrial (Q96I23). In mitochondria, S-adenosylmethionine-dependent methyltransferase chaperone that supports both coenzyme Q biosynthesis, by stabilizing its components, such as COQ5, and NADH:ubiquinone oxidoreductase complex (complex I, MT-ND1) assembly, by stabilizing complex I assembly factors…. It is a selective cancer dependency (DepMap: 26.0% of cell lines).

The product of this gene, which is well-conserved, is encoded by the same bicistronic transcript that encodes phosphatidylinositol glycan anchor biosynthesis, class Y, but the two proteins are unrelated. This gene represents the protein encoded by the upstream open reading frame, while the protein encoded by the downstream open reading frame is represented by GeneID:84992.

Source: NCBI Gene 100996939 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 1 total
• Cancer dependency (DepMap): dependent in 26.0% of screened cell lines
• MANE Select transcript: NM_032906

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:44317
Approved symbol	PYURF
Name	PIGY upstream open reading frame
Location	4q22.1
Locus type	gene with protein product
Status	Approved
Aliases	PreY
Ensembl gene	ENSG00000145337
Ensembl biotype	protein_coding
OMIM	619956
Entrez	100996939

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000273968

RefSeq mRNA: 1 — MANE Select: NM_032906 NM_032906

CCDS: CCDS3631

Canonical transcript exons

ENST00000273968 — 2 exons

Exon	Start	End
ENSE00000970016	88523498	88523776
ENSE00001244874	88520998	88522029

Expression profiles

Bgee: expression breadth ubiquitous, 143 present calls, max score 94.50.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 67.6767 / max 805.1876, expressed in 1824 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
53098	67.6767	1824

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	94.50	gold quality
spinal cord	UBERON:0002240	94.21	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.21	gold quality
smooth muscle tissue	UBERON:0001135	94.11	gold quality
body of pancreas	UBERON:0001150	94.11	gold quality
pancreas	UBERON:0001264	94.03	gold quality
left adrenal gland	UBERON:0001234	93.82	gold quality
left coronary artery	UBERON:0001626	93.81	gold quality
left uterine tube	UBERON:0001303	93.78	gold quality
right adrenal gland cortex	UBERON:0035827	93.78	gold quality
left adrenal gland cortex	UBERON:0035825	93.72	gold quality
monocyte	CL:0000576	93.67	gold quality
leukocyte	CL:0000738	93.67	gold quality
right adrenal gland	UBERON:0001233	93.66	gold quality
descending thoracic aorta	UBERON:0002345	93.62	gold quality
endometrium	UBERON:0001295	93.61	gold quality
popliteal artery	UBERON:0002250	93.57	gold quality
fallopian tube	UBERON:0003889	93.57	gold quality
tibial artery	UBERON:0007610	93.57	gold quality
substantia nigra	UBERON:0002038	93.48	gold quality
body of uterus	UBERON:0009853	93.44	gold quality
hypothalamus	UBERON:0001898	93.37	gold quality
subcutaneous adipose tissue	UBERON:0002190	93.36	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.35	gold quality
ectocervix	UBERON:0012249	93.31	gold quality
adipose tissue	UBERON:0001013	93.27	gold quality
ventricular zone	UBERON:0003053	93.26	gold quality
thoracic aorta	UBERON:0001515	93.22	gold quality
omental fat pad	UBERON:0010414	93.18	gold quality
ascending aorta	UBERON:0001496	93.17	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-10042	yes	5.67
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

75 targeting PYURF, 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-6833-3P	100.00	70.63	3197
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-6757-3P	99.63	66.88	1089
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-105-5P	99.54	69.24	2060

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 26.0% of screened cell lines.

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
danio_rerio	PYURF	ENSDARG00000045773
rattus_norvegicus	Pyurf	ENSRNOG00000006858

Protein

Protein identifiers

Protein preY, mitochondrial — Q96I23 (reviewed: Q96I23)

Alternative names: PIGY upstream reading frame protein

All UniProt accessions (1): Q96I23

UniProt curated annotations — full annotation on UniProt →

Function. In mitochondria, S-adenosylmethionine-dependent methyltransferase chaperone that supports both coenzyme Q biosynthesis, by stabilizing its components, such as COQ5, and NADH:ubiquinone oxidoreductase complex (complex I, MT-ND1) assembly, by stabilizing complex I assembly factors, such as NDUFAF5.

Subunit / interactions. Interacts (via TRM112 domain) with NDUFAF5; the interaction is direct and stabilizes NDUFAF5 protein. Interacts with COQ5; the interaction is direct, stabilizes COQ5 protein and associates PYURF with COQ enzyme complex.

Subcellular location. Mitochondrion.

Disease relevance. An homozygous frameshift variant in the second exon of PYURF have been found in a patient with profound metabolic acidosis and clinical features including muscle hypotonia, failure to thrive, developmental delay, optic atrophy, persistently elevated lactate levels in the blood and cerebrospinal fluid, and abnormal cerebellar white matter and cerebellar atrophy on magnetic resonance imaging.

Miscellaneous. PREY and PIGY, 2 apparently unrelated proteins, are respectively the product of an upstream and a downstream ORF contained in a single bicistronic transcript.

Similarity. Belongs to the PREY family.

RefSeq proteins (1): NP_116295* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005651	Trm112-like	Family

Pfam: PF03966

UniProt features (8 total): mutagenesis site 3, transit peptide 1, 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-Q96I23-F1	77.09	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.

Mutagenesis-validated functional residues (3):

Position	Phenotype
58	loss of interaction with ndufaf5.
60	reduces interaction with ndufaf5.
91	reduces interaction with ndufaf5.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6799198	Complex I biogenesis

MSigDB gene sets: 44 (showing top): GOBP_PROTEIN_STABILIZATION, GOBP_REGULATION_OF_PROTEIN_STABILITY, chr4q22, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOCC_ORGANELLE_SUBCOMPARTMENT, DELACROIX_RARG_BOUND_MEF, REACTOME_COMPLEX_I_BIOGENESIS, CSHL1_TARGET_GENES, TOP2B_TARGET_GENES, ZNF7_TARGET_GENES, ZNF711_TARGET_GENES, MIR548E_5P, MIR6809_3P, MIR137_3P, MIR5680

GO Biological Process (1): protein stabilization (GO:0050821)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): mitochondrion (GO:0005739), endoplasmic reticulum membrane (GO:0005789)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Respiratory electron transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of protein stability	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1

Protein interactions and networks

STRING

408 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PYURF	PIGY	Q3MUY2	911
PYURF	PIGP	P57054	882
PYURF	PIGH	Q14442	840
PYURF	PIGC	Q92535	840
PYURF	PIGA	P37287	828
PYURF	PIGQ	Q9BRB3	807
PYURF	DPM2	O94777	805
PYURF	NDUFAF5	Q5TEU4	544
PYURF	BEAN1	Q3B7T3	532
PYURF	FAM13A	O94988	530
PYURF	ZNF608	Q9ULD9	504
PYURF	RIMS4	Q9H426	501
PYURF	TUBGCP4	Q9UGJ1	490
PYURF	TRUB2	O95900	474
PYURF	PCYOX1	Q9UHG3	471

IntAct

5 interactions, top by confidence:

A	B	Type	Score
COQ5	COQ9	psi-mi:“MI:0914”(association)	0.590
PB2		psi-mi:“MI:0914”(association)	0.350
	VWA8	psi-mi:“MI:2364”(proximity)	0.270
PDK1	VWA8	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (7): PYURF (Affinity Capture-MS), PYURF (Proximity Label-MS), PYURF (Co-fractionation), HEBP1 (Co-fractionation), HINT2 (Co-fractionation), PYURF (Co-fractionation), PYURF (Co-fractionation)

ESM2 similar proteins: A4D161, B1AR13, D3ZV31, E1BBQ2, E1BGQ2, F1N2W9, O42148, O42224, O70524, O95453, P0C7P0, P56726, P97698, Q2T9V7, Q3UGM2, Q497H0, Q56K12, Q5RC51, Q5T6S3, Q5U2M7, Q5XII8, Q5ZIA0, Q60769, Q66J85, Q6DDJ3, Q6DJB3, Q6ZN54, Q7T0P6, Q7Z2E3, Q8BKW4, Q8BYN3, Q8CCA0, Q8IWR0, Q8K214, Q8K2I9, Q8NE86, Q8NFZ0, Q8TDW4, Q92564, Q96GD3

Diamond homologs: A0K9W9, A1B4L5, A1TQ98, A1V115, A1W893, A1WSH4, A2S514, A3MN46, A3N6K6, A3NS89, A3PFZ5, A4JH78, A4WWL8, A4YK44, A5CVZ8, A5E8U9, A5VVG4, A5W727, A6UDZ3, A6V3B8, A6X438, A9AGK3, A9BWI3, A9H298, A9MCH2, A9WVQ6, B0KF42, B0UM25, B1J507, B1JXF6, B1YVD8, B2JDV3, B2SAE8, B2T6M2, B3PR35, B3Q881, B4E9F9, B5ZTJ9, B7V148, B8GR39

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	0
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

236 predictions. Top by Δscore:

Variant	Effect	Δscore
4:88522025:CATAT:C	acceptor_gain	1.0000
4:88522027:TAT:T	acceptor_gain	1.0000
4:88522030:C:CC	acceptor_gain	1.0000
4:88522035:G:GC	acceptor_gain	1.0000
4:88523495:TACCT:T	donor_loss	1.0000
4:88523496:ACCTG:A	donor_loss	1.0000
4:88523497:C:CG	donor_loss	1.0000
4:88522028:AT:A	acceptor_gain	0.9900
4:88522029:TCTGA:T	acceptor_loss	0.9900
4:88522030:C:A	acceptor_loss	0.9900
4:88522031:T:A	acceptor_loss	0.9900
4:88522035:G:C	acceptor_gain	0.9900
4:88522899:T:C	donor_gain	0.9900
4:88523496:A:AC	donor_gain	0.9900
4:88523497:C:CC	donor_gain	0.9900
4:88522888:A:AC	donor_gain	0.9700
4:88522889:C:CC	donor_gain	0.9700
4:88522026:ATAT:A	acceptor_gain	0.9600
4:88523508:T:TA	donor_gain	0.9400
4:88522105:C:CT	donor_gain	0.9300
4:88522881:CAACA:C	donor_gain	0.9200
4:88522882:AACAA:A	donor_gain	0.9200
4:88522860:TTC:T	donor_gain	0.8900
4:88522890:T:C	donor_gain	0.8900
4:88522856:CACTT:C	donor_gain	0.8200
4:88522861:T:A	donor_gain	0.8200
4:88522884:CA:C	donor_gain	0.8100
4:88522885:AA:A	donor_gain	0.8100
4:88522816:G:C	donor_gain	0.8000
4:88522980:TAGGG:T	donor_gain	0.8000

AlphaMissense

722 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:88522006:A:G	L76S	0.969
4:88521961:A:G	I91T	0.949
4:88521999:A:C	N78K	0.947
4:88521999:A:T	N78K	0.947
4:88523509:C:A	K64N	0.941
4:88523509:C:G	K64N	0.941
4:88523523:A:G	C60R	0.939
4:88523513:G:A	S63F	0.933
4:88521937:G:T	A99D	0.919
4:88521961:A:C	I91S	0.913
4:88521964:C:A	G90V	0.913
4:88521973:A:T	I87N	0.912
4:88523501:A:T	L67H	0.911
4:88521973:A:C	I87S	0.910
4:88521959:G:A	P92S	0.903
4:88521980:A:C	Y85D	0.901
4:88521958:G:T	P92H	0.900
4:88521951:C:A	M94I	0.899
4:88521951:C:G	M94I	0.899
4:88521951:C:T	M94I	0.899
4:88521973:A:G	I87T	0.890
4:88523522:C:G	C60S	0.887
4:88523523:A:T	C60S	0.887
4:88521952:A:G	M94T	0.886
4:88523521:G:C	C60W	0.885
4:88521982:G:T	A84D	0.880
4:88521980:A:G	Y85H	0.877
4:88521959:G:T	P92T	0.876
4:88523530:G:C	F57L	0.876
4:88523530:G:T	F57L	0.876

dbSNP variants (sampled 300 via entrez): RS1000114967 (4:88524116 A>G), RS1001758000 (4:88522465 G>A), RS1002219622 (4:88520843 G>C), RS1002830216 (4:88524919 T>C), RS1002909692 (4:88523771 G>C,T), RS1002960516 (4:88524597 G>A), RS1004315038 (4:88520856 C>T), RS1004791959 (4:88524244 G>T), RS1005938437 (4:88524735 G>A,C), RS1006383836 (4:88525002 G>GT), RS1007645802 (4:88523822 C>G,T), RS1007950891 (4:88521933 C>A), RS1008028290 (4:88523657 C>A,T), RS1008397665 (4:88522297 T>C), RS1009023330 (4:88524010 T>C)

Disease associations

OMIM: gene MIM:619956 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST005956_59	Waist-to-hip ratio adjusted for BMI	5.000000e-08
GCST005957_14	Waist-to-hip ratio adjusted for BMI (age <50)	2.000000e-06
GCST005962_35	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	2.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement

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
sodium arsenite	decreases expression	2
aristolochic acid I	increases expression	1
di-n-butylphosphoric acid	affects expression	1
Acetaminophen	decreases expression	1
Cadmium	decreases expression	1
Doxorubicin	increases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_TH87	HAP1 PYURF (-) 1	Cancer cell line	Male
CVCL_TH88	HAP1 PYURF (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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