YBEY

Summary

YBEY (ybeY metalloendoribonuclease, HGNC:1299) is a protein-coding gene on chromosome 21q22.3, encoding Endoribonuclease YbeY (P58557). Single strand-specific metallo-endoribonuclease involved in rRNA maturation.

This gene encodes a highly conserved metalloprotein. A similar protein in bacteria acts as an endoribonuclease, and is thought to function in ribosomal RNA maturation and ribosome assembly. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 54059 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 32 total
• MANE Select transcript: NM_001314025

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1299
Approved symbol	YBEY
Name	ybeY metalloendoribonuclease
Location	21q22.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000182362
Ensembl biotype	protein_coding
OMIM	617461
Entrez	54059

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 22 protein_coding, 2 retained_intron

ENST00000329319, ENST00000339195, ENST00000397691, ENST00000397692, ENST00000397694, ENST00000397701, ENST00000468924, ENST00000492864, ENST00000903442, ENST00000903443, ENST00000903444, ENST00000921775, ENST00000921776, ENST00000921777, ENST00000921778, ENST00000921779, ENST00000921780, ENST00000921781, ENST00000921782, ENST00000921783, ENST00000921784, ENST00000921785, ENST00000921786, ENST00000949821

RefSeq mRNA: 7 — MANE Select: NM_001314025 NM_001006114, NM_001314022, NM_001314023, NM_001314024, NM_001314025, NM_001314026, NM_058181

CCDS: CCDS33591, CCDS82685, CCDS82686, CCDS82687

Canonical transcript exons

ENST00000397701 — 5 exons

Exon	Start	End
ENSE00001302401	46291334	46291462
ENSE00001322578	46296162	46296230
ENSE00001529749	46297539	46297751
ENSE00001820637	46286342	46286415
ENSE00003566287	46286870	46287123

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 95.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.7270 / max 370.8697, expressed in 1803 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
189702	12.0004	1795
189704	1.9957	1187
189703	1.0971	543
189700	0.6046	326
189701	0.0292	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	95.98	gold quality
right testis	UBERON:0004534	95.51	gold quality
testis	UBERON:0000473	94.76	gold quality
cardiac muscle of right atrium	UBERON:0003379	92.49	silver quality
left ventricle myocardium	UBERON:0006566	92.31	gold quality
sperm	CL:0000019	92.10	gold quality
kidney epithelium	UBERON:0004819	90.46	silver quality
caput epididymis	UBERON:0004358	90.10	gold quality
corpus epididymis	UBERON:0004359	89.31	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	89.27	gold quality
spinal cord	UBERON:0002240	88.85	gold quality
islet of Langerhans	UBERON:0000006	88.83	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.51	gold quality
pons	UBERON:0000988	88.28	gold quality
tibialis anterior	UBERON:0001385	87.90	gold quality
superior vestibular nucleus	UBERON:0007227	87.70	gold quality
myocardium	UBERON:0002349	87.32	silver quality
granulocyte	CL:0000094	87.14	gold quality
body of tongue	UBERON:0011876	87.11	gold quality
adult organism	UBERON:0007023	87.10	gold quality
inferior vagus X ganglion	UBERON:0005363	86.96	gold quality
ileal mucosa	UBERON:0000331	86.91	gold quality
upper arm skin	UBERON:0004263	86.77	silver quality
subthalamic nucleus	UBERON:0001906	86.69	gold quality
cauda epididymis	UBERON:0004360	86.59	gold quality
monocyte	CL:0000576	86.42	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.40	gold quality
leukocyte	CL:0000738	86.40	gold quality
mucosa of transverse colon	UBERON:0004991	86.37	gold quality
hypothalamus	UBERON:0001898	85.84	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.34

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, ZGPAT, ZNF91

miRNA regulators (miRDB)

6 targeting YBEY, 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-651-3P	99.94	73.48	5177
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-6826-3P	98.19	66.32	1153
HSA-MIR-1298-5P	95.96	64.81	573
HSA-MIR-6795-3P	91.86	63.00	218

Literature-anchored findings (GeneRIF, showing 4)

• This observation suggests that the function of HuYbeY in human cells is likely regulated through specific interactions with partner proteins similarly to the way YbeY is regulated in bacteria. (PMID:28153719)
• YBEY is an essential biogenesis factor for mitochondrial ribosomes. (PMID:32182356)
• YbeY, eminence grise of ribosome biogenesis. (PMID:33929506)
• YbeY is required for ribosome small subunit assembly and tRNA processing in human mitochondria. (PMID:34037799)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ybey	ENSDARG00000011999
		ENSDARG00000110510
mus_musculus	Ybey	ENSMUSG00000033126
rattus_norvegicus	Ybey	ENSRNOG00000021365
drosophila_melanogaster	Brd7-9	FBGN0031947
caenorhabditis_elegans	swsn-9	WBGENE00007256

Paralogs (2): BRD9 (ENSG00000028310), BRD7 (ENSG00000166164)

Protein

Protein identifiers

Endoribonuclease YbeY — P58557 (reviewed: P58557)

All UniProt accessions (1): P58557

UniProt curated annotations — full annotation on UniProt →

Function. Single strand-specific metallo-endoribonuclease involved in rRNA maturation.

Subcellular location. Nucleus.

Cofactor. Binds 1 zinc ion.

Miscellaneous. A protein of the expected size has been detected by antibody binding and Western blot in at least one of the analyzed tissues or cells.

Similarity. Belongs to the endoribonuclease YbeY family.

Isoforms (4)

UniProt ID	Names	Canonical?
P58557-1	A	yes
P58557-2	B
P58557-3	C
P58557-4	D

RefSeq proteins (5): NP_001300951, NP_001300952, NP_001300953, NP_001300954, NP_478061 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002036	YbeY	Family
IPR020549	YbeY_CS	Conserved_site
IPR023091	MetalPrtase_cat_dom_sf_prd	Homologous_superfamily

Pfam: PF02130

UniProt features (10 total): binding site 3, splice variant 3, mutagenesis site 3, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P58557-F1	96.39	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.

Ligand- & substrate-binding residues (3): 118; 122; 128

Mutagenesis-validated functional residues (3):

Position	Phenotype
55	no endonuclease activity.
90	no endonuclease activity.
118	no endonuclease activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 68 (showing top): GOBP_RIBOSOME_BIOGENESIS, GOMF_ENDONUCLEASE_ACTIVITY, GOMF_RNA_NUCLEASE_ACTIVITY, GOMF_METALLOPEPTIDASE_ACTIVITY, GOMF_NUCLEASE_ACTIVITY, GOMF_RNA_ENDONUCLEASE_ACTIVITY, chr21q22, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, GOMF_PEPTIDASE_ACTIVITY, GOMF_CATALYTIC_ACTIVITY_ACTING_ON_RNA, ALKBH3_TARGET_GENES, ELF2_TARGET_GENES, ID2_TARGET_GENES, KAT2A_TARGET_GENES, PCGF1_TARGET_GENES

GO Biological Process (1): rRNA processing (GO:0006364)

GO Molecular Function (7): metalloendopeptidase activity (GO:0004222), RNA endonuclease activity (GO:0004521), metal ion binding (GO:0046872), nuclease activity (GO:0004518), endonuclease activity (GO:0004519), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (2): nucleus (GO:0005634), mitochondrion (GO:0005739)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	2
RNA processing	1
rRNA metabolic process	1
ribosome biogenesis	1
endopeptidase activity	1
metallopeptidase activity	1
endonuclease activity	1
RNA nuclease activity	1
cation binding	1
catalytic activity, acting on a nucleic acid	1
nuclease activity	1
binding	1
catalytic activity	1
cytoplasm	1

Protein interactions and networks

STRING

1859 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
YBEY	PNPT1	Q8TCS8	713
YBEY	RWDD2B	P57060	631
YBEY	PCBP3	P57721	610
YBEY	RGP1	Q92546	605
YBEY	C21orf58	P58505	577
YBEY	ERAL1	O75616	575
YBEY	POFUT2	Q9Y2G5	575
YBEY	ELAC2	Q9BQ52	545
YBEY	REXO2	Q9Y3B8	543
YBEY	MCM3AP	O60318	542
YBEY	RPS14	P06366	513
YBEY	CUTC	Q9NTM9	509
YBEY	LACTB2	Q53H82	502
YBEY	MRPS6	P82932	501
YBEY	MRPL36	Q9P0J6	497

IntAct

25 interactions, top by confidence:

A	B	Type	Score
DSN1	ZWINT	psi-mi:“MI:0914”(association)	0.900
MIS12	ZWINT	psi-mi:“MI:0914”(association)	0.900
YBEY	BCAT2	psi-mi:“MI:0915”(physical association)	0.670
RPS2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
CBX5	WIZ	psi-mi:“MI:0914”(association)	0.530
L3MBTL1	DNAJB6	psi-mi:“MI:0914”(association)	0.530
YBEY	NME4	psi-mi:“MI:0914”(association)	0.530
YBEY	AKTIP	psi-mi:“MI:0915”(physical association)	0.370
YBEY	NUDT19	psi-mi:“MI:0914”(association)	0.350
SSH3	HSPA8	psi-mi:“MI:0914”(association)	0.350
HAUS2	FLNB	psi-mi:“MI:0914”(association)	0.350
L3MBTL4	GAPDHS	psi-mi:“MI:0914”(association)	0.350
TUBGCP4	SPTLC1	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
CARTPT	MEIS1	psi-mi:“MI:0914”(association)	0.350
GAS2L2	ANKRD17	psi-mi:“MI:0914”(association)	0.350
NUBP1	YBEY	psi-mi:“MI:0914”(association)	0.350
CARTPT	LAMC1	psi-mi:“MI:0914”(association)	0.350
KRT33B	EPPK1	psi-mi:“MI:0914”(association)	0.350
Smad6	DDX1	psi-mi:“MI:0914”(association)	0.350
	TBKBP1	psi-mi:“MI:0914”(association)	0.350
YBEY	GEM	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (141): YBEY (Affinity Capture-MS), YBEY (Affinity Capture-MS), YBEY (Affinity Capture-MS), YBEY (Affinity Capture-MS), YBEY (Affinity Capture-MS), YBEY (Affinity Capture-MS), YBEY (Affinity Capture-MS), YBEY (Affinity Capture-MS), YBEY (Affinity Capture-MS), YBEY (Affinity Capture-MS), YBEY (Affinity Capture-MS), BCAT2 (Affinity Capture-MS), GTPBP8 (Affinity Capture-MS), TRMU (Affinity Capture-MS), GFM2 (Affinity Capture-MS)

ESM2 similar proteins: A2VE14, B1H1Z8, B1WC68, B4ZIX8, O43913, O54865, O75648, P16068, P20595, P52848, P58557, Q02153, Q02353, Q0VCB2, Q0VCJ8, Q13635, Q1M199, Q3SZB3, Q3U129, Q3UHN9, Q3ZCQ8, Q4R4U1, Q4ZHR9, Q5E9U9, Q5NVN7, Q5R5F8, Q5ZMH6, Q61115, Q6AXQ0, Q6AYR2, Q7Z6J6, Q8BTG7, Q8CAV0, Q8VH37, Q8WTW4, Q91YQ7, Q923S8, Q96G75, Q9BY41, Q9CQC8

Diamond homologs: A0RIS3, A1QYL0, A1UU41, A3DEC2, A3PAQ0, A4IR19, A4J7D9, A4XKI9, A5IT98, A6Q9R0, A6QHB3, A6TSK3, A6U242, A6WWX4, A7GSZ7, A7X2W8, A7Z6U6, A8FFB6, A8IG05, A8MG66, A8Z4A9, A9IMW1, A9KMV9, A9M9Y5, A9NGT0, A9VHT0, B0CK02, B0K706, B0KA56, B1HTJ4, B7HCS7, B7HPK2, B7IYF4, B7J0Z6, B7JN28, B8DE46, B8FUL3, B9DNL6, B9E6W1, B9IY70

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	21
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

892 predictions. Top by Δscore:

Variant	Effect	Δscore
21:46286975:G:GG	donor_gain	1.0000
21:46286985:GATT:G	donor_gain	1.0000
21:46286994:G:GT	donor_gain	0.9900
21:46291459:GACT:G	donor_gain	0.9900
21:46291463:G:GG	donor_gain	0.9900
21:46296156:TGACA:T	acceptor_loss	0.9900
21:46296157:GACA:G	acceptor_loss	0.9900
21:46296158:ACAG:A	acceptor_loss	0.9900
21:46296159:CA:C	acceptor_loss	0.9900
21:46296160:A:T	acceptor_loss	0.9900
21:46296429:A:T	donor_gain	0.9900
21:46287119:ATGAG:A	donor_loss	0.9800
21:46287120:TGAG:T	donor_loss	0.9800
21:46287121:GAGGT:G	donor_loss	0.9800
21:46287122:AGGT:A	donor_loss	0.9800
21:46287123:GGT:G	donor_loss	0.9800
21:46287124:G:GA	donor_loss	0.9800
21:46287125:T:A	donor_loss	0.9800
21:46296160:A:AG	acceptor_gain	0.9800
21:46296161:G:GG	acceptor_gain	0.9800
21:46296229:AGGT:A	donor_loss	0.9800
21:46296230:GGTAA:G	donor_loss	0.9800
21:46296231:GT:G	donor_loss	0.9800
21:46286857:A:AG	acceptor_gain	0.9700
21:46286865:CCCAG:C	acceptor_loss	0.9700
21:46286866:CCAGG:C	acceptor_loss	0.9700
21:46286867:CAGGT:C	acceptor_loss	0.9700
21:46286868:A:G	acceptor_loss	0.9700
21:46286869:G:A	acceptor_loss	0.9700
21:46286959:A:T	donor_gain	0.9700

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000104642 (21:46287421 C>G,T), RS1000292264 (21:46303290 G>C), RS1000410052 (21:46300076 T>C), RS1000470171 (21:46298234 C>T), RS1000642637 (21:46303610 G>A), RS1000647481 (21:46290207 T>G), RS1000758402 (21:46294973 C>A,G), RS1000900191 (21:46304237 A>G), RS1000984634 (21:46295073 T>A,C), RS1001035102 (21:46288686 A>G), RS1001108108 (21:46288505 G>A), RS1001221277 (21:46312901 A>G), RS1001242868 (21:46302411 G>A,T), RS1001292247 (21:46298026 C>T), RS1001327541 (21:46308420 C>T)

Disease associations

OMIM: gene MIM:617461 | 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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression, affects cotreatment	6
methylmercuric chloride	increases expression, affects cotreatment	2
ginger extract	decreases reaction, increases abundance, increases expression	1
bisphenol A	increases expression, decreases reaction, increases abundance	1
beta-lapachone	decreases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
ICG 001	decreases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Cadmium	decreases expression, increases abundance	1
Carbamazepine	affects expression	1
Estradiol	decreases expression	1
Gallic Acid	decreases expression	1
Manganese	increases abundance, affects cotreatment, decreases expression	1
Oils, Volatile	decreases reaction, increases abundance, increases expression	1
Tretinoin	decreases expression	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	decreases expression, increases abundance	1
Lactic Acid	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_TY43	HAP1 YBEY (-) 1	Cancer cell line	Male
CVCL_TY44	HAP1 YBEY (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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