YPEL4

Summary

YPEL4 (yippee like 4, HGNC:18328) is a protein-coding gene on chromosome 11q12.1, encoding Protein yippee-like 4 (Q96NS1).

Predicted to enable metal ion binding activity. Predicted to act upstream of or within several processes, including negative regulation of erythrocyte clearance; negative regulation of erythrocyte differentiation; and protein localization to plasma membrane. Predicted to be located in nucleolus.

Source: NCBI Gene 219539 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• MANE Select transcript: NM_145008

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18328
Approved symbol	YPEL4
Name	yippee like 4
Location	11q12.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ30213
Ensembl gene	ENSG00000166793
Ensembl biotype	protein_coding
OMIM	609725
Entrez	219539

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 4 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000300022, ENST00000524592, ENST00000524669, ENST00000528797, ENST00000529776, ENST00000531442, ENST00000532314, ENST00000533025, ENST00000534711, ENST00000534810

RefSeq mRNA: 2 — MANE Select: NM_145008 NM_001363487, NM_145008

CCDS: CCDS7963

Canonical transcript exons

ENST00000300022 — 5 exons

Exon	Start	End
ENSE00001106620	57646751	57646794
ENSE00001264389	57649685	57649912
ENSE00003462096	57646297	57646405
ENSE00003512252	57646967	57647291
ENSE00003849631	57645087	57646070

Expression profiles

Bgee: expression breadth ubiquitous, 190 present calls, max score 96.68.

FANTOM5 (CAGE): breadth broad, TPM avg 4.8503 / max 617.2054, expressed in 642 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
119807	4.4270	600
119808	0.2714	89
119806	0.1520	87

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	96.68	gold quality
cerebellar hemisphere	UBERON:0002245	96.47	gold quality
cerebellar cortex	UBERON:0002129	96.42	gold quality
cerebellum	UBERON:0002037	96.19	gold quality
right frontal lobe	UBERON:0002810	93.81	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.57	gold quality
cerebellar vermis	UBERON:0004720	93.08	gold quality
primary visual cortex	UBERON:0002436	92.91	gold quality
prefrontal cortex	UBERON:0000451	92.48	gold quality
frontal cortex	UBERON:0001870	92.26	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	91.89	gold quality
middle temporal gyrus	UBERON:0002771	91.67	gold quality
neocortex	UBERON:0001950	91.39	gold quality
occipital lobe	UBERON:0002021	91.26	gold quality
anterior cingulate cortex	UBERON:0009835	91.25	gold quality
cerebral cortex	UBERON:0000956	90.16	gold quality
superior frontal gyrus	UBERON:0002661	89.93	gold quality
trabecular bone tissue	UBERON:0002483	89.53	gold quality
postcentral gyrus	UBERON:0002581	89.46	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.35	gold quality
parietal lobe	UBERON:0001872	89.09	gold quality
amygdala	UBERON:0001876	88.57	gold quality
hypothalamus	UBERON:0001898	88.57	gold quality
brain	UBERON:0000955	88.48	gold quality
lateral nuclear group of thalamus	UBERON:0002736	88.37	gold quality
pons	UBERON:0000988	88.25	gold quality
forebrain	UBERON:0001890	87.83	gold quality
Ammon’s horn	UBERON:0001954	87.82	gold quality
temporal lobe	UBERON:0001871	87.73	gold quality
Brodmann (1909) area 46	UBERON:0006483	87.45	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-10042	yes	24.81
E-ANND-3	no	1.49

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

104 targeting YPEL4, 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-3924	100.00	72.09	2394
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-6825-5P	99.96	69.81	3431
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-93-5P	99.88	73.98	2606
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-3681-5P	99.82	66.88	387
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-4319	99.76	69.83	2586

Literature-anchored findings (GeneRIF, showing 2)

• Data show that major vault protein (MVP), a lung resistance associated protein, is a binding partner of YPEL4. (PMID:20555386)
• Results demonstrated that YPEL4 stimulates human adrenal cortical cell proliferation, increasing aldosterone production. Also, YPEL4 expression levels are higher in human aldosterone producing adenoma. (PMID:27333825)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ypel4	ENSMUSG00000034059
rattus_norvegicus	Ypel4	ENSRNOG00000069900
drosophila_melanogaster	l(2)37Bb	FBGN0002021
drosophila_melanogaster	CG3270	FBGN0033093
caenorhabditis_elegans		WBGENE00010847

Paralogs (10): L2HGDH (ENSG00000087299), YPEL3 (ENSG00000090238), PDPR (ENSG00000090857), YPEL1 (ENSG00000100027), FOXRED1 (ENSG00000110074), YPEL5 (ENSG00000119801), SARDH (ENSG00000123453), DMGDH (ENSG00000132837), AMT (ENSG00000145020), YPEL2 (ENSG00000175155)

Protein

Protein identifiers

Protein yippee-like 4 — Q96NS1 (reviewed: Q96NS1)

All UniProt accessions (3): Q96NS1, E9PNP5, E9PRC4

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus. Nucleolus.

Tissue specificity. Widely expressed. Detected adult brain, lung, colon, small intestine and ovary, and in fetal brain, lung, liver and spleen.

Similarity. Belongs to the yippee family.

RefSeq proteins (2): NP_001350416, NP_659445* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF03226

UniProt features (9 total): binding site 4, modified residue 3, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96NS1-F1	87.45	0.76

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): 31; 34; 87; 90

Post-translational modifications (3): 92, 93, 98

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 150 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, LFA1_Q6, GCANCTGNY_MYOD_Q6, GOBP_ERYTHROCYTE_HOMEOSTASIS, CHX10_01, GGGTGGRR_PAX4_03, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, AGGCACT_MIR5153P, GOBP_NEGATIVE_REGULATION_OF_TISSUE_REMODELING, GOBP_REGULATION_OF_HEMOPOIESIS, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, CATTTCA_MIR203

GO Biological Process (4): regulation of cell shape (GO:0008360), negative regulation of erythrocyte clearance (GO:0034107), negative regulation of erythrocyte differentiation (GO:0045647), protein localization to plasma membrane (GO:0072659)

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
regulation of cell morphogenesis	1
regulation of biological quality	1
negative regulation of immune system process	1
erythrocyte clearance	1
negative regulation of tissue remodeling	1
regulation of erythrocyte clearance	1
erythrocyte differentiation	1
negative regulation of myeloid cell differentiation	1
regulation of erythrocyte differentiation	1
protein localization to membrane	1
protein localization to cell periphery	1
cation binding	1
nuclear lumen	1
intracellular membraneless organelle	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

584 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
YPEL4	MACO1	Q8N5G2	499
YPEL4	DEDD2	Q8WXF8	445
YPEL4	OR9G4	Q8NGQ1	430
YPEL4	PPP1R10	Q96QC0	428
YPEL4	OR6K2	Q8NGY2	418
YPEL4	OR4K15	Q8NH41	417
YPEL4	RANBP10	Q6VN20	416
YPEL4	LCMT1	Q9UIC8	380
YPEL4	OR2T6	Q8NHC8	378
YPEL4	TTF2	Q9UNY4	374
YPEL4	SLC25A12	O75746	374
YPEL4	OR52B2	Q96RD2	370
YPEL4	OR52M1	Q8NGK5	357
YPEL4	OR2M3	Q8NG83	349
YPEL4	TMX2	Q9Y320	348
YPEL4	ZDHHC5	Q9C0B5	348

IntAct

0 interactions, top by confidence:

BioGRID (1): YPEL4 (Affinity Capture-RNA)

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

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1022 predictions. Top by Δscore:

Variant	Effect	Δscore
11:57646750:CA:C	donor_gain	1.0000
11:57646068:CTC:C	acceptor_gain	0.9900
11:57646071:C:A	acceptor_loss	0.9900
11:57646071:C:CC	acceptor_gain	0.9900
11:57646072:T:A	acceptor_loss	0.9900
11:57646074:G:C	acceptor_gain	0.9900
11:57646749:A:AC	donor_gain	0.9900
11:57646750:C:CC	donor_gain	0.9900
11:57646750:CACGG:C	donor_gain	0.9900
11:57646795:C:CC	acceptor_gain	0.9900
11:57646962:CGTA:C	donor_loss	0.9900
11:57646963:GTAC:G	donor_loss	0.9900
11:57646964:TACCT:T	donor_loss	0.9900
11:57646965:A:C	donor_loss	0.9900
11:57646961:GCGTA:G	donor_loss	0.9800
11:57646792:GGA:G	acceptor_gain	0.9700
11:57646793:GA:G	acceptor_gain	0.9700
11:57646750:CACG:C	donor_gain	0.9600
11:57646983:T:C	donor_gain	0.9500
11:57647292:C:CC	acceptor_gain	0.9500
11:57647673:C:CT	acceptor_gain	0.9500
11:57646074:G:GC	acceptor_gain	0.9400
11:57646744:GACT:G	donor_loss	0.9400
11:57646745:ACTC:A	donor_loss	0.9400
11:57646746:C:A	donor_loss	0.9400
11:57646747:TCAC:T	donor_loss	0.9400
11:57646748:C:CC	donor_loss	0.9400
11:57646749:AC:A	donor_loss	0.9400
11:57647289:CACCT:C	acceptor_loss	0.9400
11:57647292:CT:C	acceptor_loss	0.9400

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000479226 (11:57651766 C>T), RS1000703737 (11:57645975 A>T), RS1001117393 (11:57646283 C>A,T), RS1001192238 (11:57646608 C>A), RS1001365847 (11:57648781 C>T), RS1001473544 (11:57646893 C>T), RS1002381936 (11:57647602 G>A), RS1003029114 (11:57649524 A>T), RS1003045808 (11:57650341 T>C), RS1003542257 (11:57645304 C>T), RS1003604022 (11:57644636 G>A,C), RS1004892816 (11:57650613 T>C), RS1005049485 (11:57644900 A>G), RS1005546959 (11:57647808 A>T), RS1005558396 (11:57647562 G>A)

Disease associations

OMIM: gene MIM:609725 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002539_6	Schizophrenia	2.000000e-09
GCST004521_290	Autism spectrum disorder or schizophrenia	5.000000e-08
GCST004946_35	Schizophrenia	9.000000e-09
GCST005232_71	Neuroticism	7.000000e-11
GCST006803_71	Schizophrenia	1.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007660	neuroticism measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	2
GSK-J4	increases expression	1
propionaldehyde	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
abrine	increases expression	1
jinfukang	decreases expression	1
gardiquimod	decreases reaction, decreases expression	1
Vorinostat	decreases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Tretinoin	increases expression	1
Triclosan	decreases expression	1
Tunicamycin	increases expression	1
Valproic Acid	increases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression	1
Acrylamide	decreases expression	1
Protein Kinase Inhibitors	decreases expression, decreases reaction	1

Clinical trials (associated diseases)

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