YPEL3

Summary

YPEL3 (yippee like 3, HGNC:18327) is a protein-coding gene on chromosome 16p11.2, encoding Protein yippee-like 3 (P61236). Involved in proliferation and apoptosis in myeloid precursor cells.

Predicted to enable metal ion binding activity. Involved in positive regulation of cellular senescence. Predicted to be located in nucleolus.

Source: NCBI Gene 83719 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 19 total — 2 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_031477

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18327
Approved symbol	YPEL3
Name	yippee like 3
Location	16p11.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC10500
Ensembl gene	ENSG00000090238
Ensembl biotype	protein_coding
OMIM	609724
Entrez	83719

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 8 protein_coding, 2 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000398838, ENST00000398841, ENST00000562641, ENST00000563788, ENST00000565110, ENST00000565479, ENST00000566134, ENST00000566401, ENST00000566595, ENST00000568674, ENST00000568681, ENST00000570099, ENST00000904901

RefSeq mRNA: 2 — MANE Select: NM_031477 NM_001145524, NM_031477

CCDS: CCDS42147, CCDS45459

Canonical transcript exons

ENST00000398841 — 4 exons

Exon	Start	End
ENSE00001535214	30095252	30096213
ENSE00003471970	30095103	30095146
ENSE00003621046	30094789	30094897
ENSE00003672916	30092314	30092799

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 99.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 94.4750 / max 3865.6687, expressed in 1792 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157018	93.9674	1792
157017	0.5076	255

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	99.44	gold quality
cerebellar hemisphere	UBERON:0002245	99.39	gold quality
cerebellar cortex	UBERON:0002129	99.36	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.29	gold quality
right frontal lobe	UBERON:0002810	99.27	gold quality
blood	UBERON:0000178	99.22	gold quality
cerebellum	UBERON:0002037	99.15	gold quality
granulocyte	CL:0000094	99.06	gold quality
prefrontal cortex	UBERON:0000451	99.05	gold quality
anterior cingulate cortex	UBERON:0009835	99.00	gold quality
lower esophagus mucosa	UBERON:0035834	98.89	gold quality
amygdala	UBERON:0001876	98.74	gold quality
right lung	UBERON:0002167	98.63	gold quality
frontal cortex	UBERON:0001870	98.61	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	98.55	gold quality
mucosa of stomach	UBERON:0001199	98.46	gold quality
spleen	UBERON:0002106	98.43	gold quality
neocortex	UBERON:0001950	98.40	gold quality
hypothalamus	UBERON:0001898	98.36	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.26	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.19	gold quality
skin of leg	UBERON:0001511	98.18	gold quality
postcentral gyrus	UBERON:0002581	98.14	gold quality
skin of abdomen	UBERON:0001416	98.11	gold quality
upper arm skin	UBERON:0004263	98.07	gold quality
leukocyte	CL:0000738	98.04	gold quality
nucleus accumbens	UBERON:0001882	98.02	gold quality
putamen	UBERON:0001874	98.00	gold quality
monocyte	CL:0000576	97.95	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.91	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	5.39
E-HCAD-8	no	23.72
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

29 targeting YPEL3, 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-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-370-5P	99.78	66.81	706
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-548V	99.29	69.47	1157
HSA-MIR-6735-5P	98.24	65.36	1488
HSA-MIR-6881-5P	98.16	67.38	665
HSA-MIR-4700-3P	97.74	68.64	1014
HSA-MIR-1972	97.67	67.38	1172
HSA-MIR-7106-3P	97.33	65.33	644
HSA-MIR-2278	97.30	66.19	1130
HSA-MIR-3194-5P	96.80	64.90	1027
HSA-MIR-3139	96.68	66.77	652
HSA-MIR-28-5P	96.16	66.12	579
HSA-MIR-708-5P	96.16	66.12	576
HSA-MIR-125B-1-3P	91.57	67.67	56

Literature-anchored findings (GeneRIF, showing 8)

• Findings point to YPEL3 being a novel tumor suppressor, which upon induction triggers a permanent growth arrest in human tumor and normal cells. (PMID:20388804)
• In this review we show that transcriptionally active forms of p73 and p63, family members of p53, can transactivate the human YPEL3 gene[review] (PMID:21196260)
• YPEL3 is downregulated in colon tumors. (PMID:21267786)
• YPEL3 expression, which is induced by the removal of estrogen or treatment with tamoxifen triggers cellular senescence in MCF-7 cells while loss of YPEL3 increases the growth rate of MCF-7 cells. (PMID:21671470)
• Data show that YPEL3 is downregulated in nasopharyngeal carcinoma (NPC) cell lines and tissue samples and it suppresses NPC EMT and metastasis by suppressing the Wnt/beta-catenin signaling pathway. (PMID:27400785)
• Expression of the YPEL3 gene was upregulated in human colonic adenocarcinoma tissue. (PMID:29988027)
• yippee like 3 (ypel3) is a novel gene required for myelinating and perineurial glia development. (PMID:32544203)
• Steroid sulfatase deficiency causes cellular senescence and abnormal differentiation by inducing Yippee-like 3 expression in human keratinocytes. (PMID:34675221)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ypel3	ENSDARG00000055510
mus_musculus	Ypel3	ENSMUSG00000042675
rattus_norvegicus	Ypel3	ENSRNOG00000019721

Paralogs (10): L2HGDH (ENSG00000087299), PDPR (ENSG00000090857), YPEL1 (ENSG00000100027), FOXRED1 (ENSG00000110074), YPEL5 (ENSG00000119801), SARDH (ENSG00000123453), DMGDH (ENSG00000132837), AMT (ENSG00000145020), YPEL4 (ENSG00000166793), YPEL2 (ENSG00000175155)

Protein

Protein identifiers

Protein yippee-like 3 — P61236 (reviewed: P61236)

All UniProt accessions (6): P61236, A0A0B4J290, H3BME7, H3BNP5, H3BRF0, H3BUE2

UniProt curated annotations — full annotation on UniProt →

Function. Involved in proliferation and apoptosis in myeloid precursor cells.

Subcellular location. Nucleus. Nucleolus.

Tissue specificity. Widely expressed.

Post-translational modifications. Probably ubiquitinated leading to its degradation by the proteasome.

Similarity. Belongs to the yippee family.

Isoforms (2)

UniProt ID	Names	Canonical?
P61236-1	1	yes
P61236-2	2

RefSeq proteins (2): NP_001138996, NP_113665* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004910	Yippee/Mis18/Cereblon	Domain
IPR034751	Yippee	Domain
IPR039058	Yippee_fam	Family

Pfam: PF03226

UniProt features (7 total): binding site 4, chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P61236-F1	90.46	0.78

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 (4): 23; 26; 79; 82

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 191 (showing top): WANG_CLIM2_TARGETS_UP, GOBP_CELLULAR_SENESCENCE, FERREIRA_EWINGS_SARCOMA_UNSTABLE_VS_STABLE_DN, chr16p11, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, MODULE_480, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, PPAR_DR1_Q2, TGGNNNNNNKCCAR_UNKNOWN, BRACHAT_RESPONSE_TO_CISPLATIN, YY1_01, HU_GENOTOXIN_ACTION_DIRECT_VS_INDIRECT_24HR, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_0, AGCTCCT_MIR28, MODULE_427

GO Biological Process (1): positive regulation of cellular senescence (GO:2000774)

GO Molecular Function (1): metal ion binding (GO:0046872)

GO Cellular Component (2): nucleolus (GO:0005730), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of cellular process	1
cellular senescence	1
regulation of cellular senescence	1
cation binding	1
nuclear lumen	1
intracellular membraneless organelle	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

850 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
YPEL3	ASPHD1	Q5U4P2	687
YPEL3	KCTD13	Q8WZ19	643
YPEL3	HIRIP3	Q9BW71	640
YPEL3	GDPD3	Q7L5L3	617
YPEL3	PAGR1	Q9BTK6	615
YPEL3	SEZ6L2	Q6UXD5	608
YPEL3	FIMP1	Q96LL3	607
YPEL3	INO80E	Q8NBZ0	604
YPEL3	CDIPT	O14735	598
YPEL3	C16orf54	Q6UWD8	598
YPEL3	DOC2A	Q14183	597
YPEL3	KIF22	Q14807	586
YPEL3	TMEM219	Q86XT9	574
YPEL3	PRRT2	Q7Z6L0	551
YPEL3	TAOK2	Q9UL54	529

IntAct

6 interactions, top by confidence:

A	B	Type	Score
YPEL3	SRPK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
SRPK1	YPEL3	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
YPEL3	FBXL20	psi-mi:“MI:0914”(association)	0.350
YPEL3	APAF1	psi-mi:“MI:0914”(association)	0.350
UBASH3A	YPEL3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (137): YPEL3 (Two-hybrid), YPEL3 (Two-hybrid), YPEL3 (Two-hybrid), YPEL3 (Two-hybrid), YPEL3 (Two-hybrid), YPEL3 (Two-hybrid), FBXL2 (Affinity Capture-MS), FBXL20 (Affinity Capture-MS), YPEL3 (Two-hybrid), YPEL3 (Two-hybrid), YPEL3 (Two-hybrid), YPEL3 (Two-hybrid), YPEL3 (Two-hybrid), YPEL3 (Two-hybrid), YPEL3 (Two-hybrid)

ESM2 similar proteins: A2VE01, A6QPH8, D3ZRP6, O60688, P00860, P11926, P27117, P27118, P27119, P27120, P48455, P61236, P61237, Q16HW7, Q1RMS5, Q24208, Q2YDI3, Q3SYW1, Q5EBF1, Q5PQL4, Q5RDN9, Q5VST6, Q5XID5, Q5ZIZ4, Q5ZJ01, Q65Z54, Q65Z56, Q65Z57, Q65Z58, Q65Z59, Q65Z93, Q65Z95, Q6AY17, Q6DCC5, Q6DEY3, Q6DKB0, Q6NWI4, Q7M759, Q8L5V0, Q96NS1

Diamond homologs: A6QPH8, O44440, O60688, P38191, P59234, P61236, P61237, P62699, P62700, Q2V3E2, Q2YDI3, Q3ZBE7, Q4R4Q6, Q5RDN9, Q5RDU7, Q5XID5, Q65Z54, Q65Z55, Q65Z56, Q65Z57, Q65Z58, Q65Z59, Q65Z93, Q65Z95, Q6NWI4, Q8S5M8, Q96NS1, Q96QA6, Q9C777, Q9DG42, Q9ESC7, Q9FN32, Q9LY56, Q9SR97, Q9T096, Q9U3G6, Q9URW3, Q9W2X7, Q9XZF0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	10
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1328112	GRCh37/hg19 16p11.2(chr16:29606372-30199622)x1	Pathogenic
3906925	NM_031477.5(YPEL3):c.273dup (p.Val92fs)	Pathogenic
442896	GRCh37/hg19 16p11.2(chr16:29517698-30243606)x3	Likely pathogenic

SpliceAI

1049 predictions. Top by Δscore:

Variant	Effect	Δscore
16:30094782:GACTC:G	donor_loss	1.0000
16:30094783:ACTC:A	donor_loss	1.0000
16:30094784:CTCA:C	donor_loss	1.0000
16:30094785:TCA:T	donor_loss	1.0000
16:30094786:CACAT:C	donor_loss	1.0000
16:30094787:A:AC	donor_gain	1.0000
16:30094787:ACAT:A	donor_loss	1.0000
16:30094788:C:CA	donor_gain	1.0000
16:30094788:CATA:C	donor_gain	1.0000
16:30094788:CATAT:C	donor_gain	1.0000
16:30094791:ATTT:A	donor_gain	1.0000
16:30095147:C:CC	acceptor_gain	1.0000
16:30095247:GTTA:G	donor_loss	1.0000
16:30095248:TTAC:T	donor_loss	1.0000
16:30095249:TACCT:T	donor_loss	1.0000
16:30095251:C:A	donor_loss	1.0000
16:30092796:GTTC:G	acceptor_gain	0.9900
16:30092799:CCTGA:C	acceptor_loss	0.9900
16:30092800:C:CC	acceptor_gain	0.9900
16:30092800:CT:C	acceptor_loss	0.9900
16:30094780:GTGAC:G	donor_loss	0.9900
16:30094781:TGACT:T	donor_loss	0.9900
16:30094788:CA:C	donor_gain	0.9900
16:30094893:TCACC:T	acceptor_gain	0.9900
16:30094894:CACC:C	acceptor_gain	0.9900
16:30094894:CACCC:C	acceptor_gain	0.9900
16:30094896:CC:C	acceptor_gain	0.9900
16:30094897:CCTG:C	acceptor_gain	0.9900
16:30094898:C:CC	acceptor_gain	0.9900
16:30094899:T:A	acceptor_loss	0.9900

AlphaMissense

1026 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:30092753:A:T	I106N	1.000
16:30092767:T:A	K101N	1.000
16:30092767:T:G	K101N	1.000
16:30092768:T:A	K101I	1.000
16:30092769:T:C	K101E	1.000
16:30092769:T:G	K101Q	1.000
16:30092771:T:C	Y100C	1.000
16:30092772:A:G	Y100H	1.000
16:30094790:T:C	Y90C	1.000
16:30094791:A:G	Y90H	1.000
16:30094795:C:A	W88C	1.000
16:30094795:C:G	W88C	1.000
16:30094796:C:G	W88S	1.000
16:30094797:A:G	W88R	1.000
16:30094797:A:T	W88R	1.000
16:30094799:C:A	G87V	1.000
16:30094799:C:T	G87D	1.000
16:30094800:C:G	G87R	1.000
16:30094813:G:C	C82W	1.000
16:30094814:C:T	C82Y	1.000
16:30094822:G:C	C79W	1.000
16:30094823:C:G	C79S	1.000
16:30094823:C:T	C79Y	1.000
16:30094824:A:G	C79R	1.000
16:30094824:A:T	C79S	1.000
16:30094836:C:G	A75P	1.000
16:30094838:A:T	V74D	1.000
16:30094843:A:C	H72Q	1.000
16:30094843:A:T	H72Q	1.000
16:30094845:G:C	H72D	1.000

dbSNP variants (sampled 300 via entrez): RS1000060529 (16:30094596 A>G), RS1000305364 (16:30093887 C>A,T), RS1001016523 (16:30096114 G>A), RS1001460360 (16:30094350 C>G), RS1001565006 (16:30095198 G>A), RS1001849338 (16:30094639 G>A,T), RS1002517308 (16:30096183 C>A,G,T), RS1002760744 (16:30096321 C>A,T), RS1002806697 (16:30093430 T>A), RS1002889944 (16:30093003 C>T), RS1003402098 (16:30092011 G>T), RS1003554592 (16:30095829 G>A,T), RS1003832438 (16:30096922 G>A), RS1004251911 (16:30097088 G>T), RS1004912619 (16:30092273 C>T)

Disease associations

OMIM: gene MIM:609724 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002539_82	Schizophrenia	5.000000e-11
GCST004521_236	Autism spectrum disorder or schizophrenia	4.000000e-10
GCST004946_142	Schizophrenia	8.000000e-13
GCST006803_23	Schizophrenia	6.000000e-13
GCST007293_15	Body fat distribution (arm fat ratio)	6.000000e-06
GCST007293_81	Body fat distribution (arm fat ratio)	4.000000e-08
GCST010703_269	Brain morphology (MOSTest)	4.000000e-13

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004341	body fat distribution
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	decreases methylation, increases expression	3
bisphenol A	decreases expression, affects cotreatment, increases expression	2
Acetaminophen	decreases expression, increases expression	2
Air Pollutants	increases expression, affects expression, increases abundance	2
Benzo(a)pyrene	affects methylation, increases expression	2
Cisplatin	affects cotreatment, increases expression, decreases expression	2
Estradiol	decreases expression	2
Cyclosporine	decreases expression	2
GSK-J4	increases expression	1
afuresertib	increases expression	1
bisphenol F	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
lead acetate	decreases expression	1
cannabichromene	increases expression	1
sulforaphane	decreases expression	1
sodium arsenite	increases expression	1
cupric chloride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects response to substance	1
perfluoro-n-nonanoic acid	decreases expression	1
clothianidin	decreases expression	1
nutlin 3	affects cotreatment, increases expression	1
ICG 001	decreases expression	1
abrine	decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases expression, increases response to substance	1
jinfukang	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Camptothecin	increases expression	1
Cannabidiol	increases expression	1

Clinical trials (associated diseases)

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