PPP1R15B

Summary

PPP1R15B (protein phosphatase 1 regulatory subunit 15B, HGNC:14951) is a protein-coding gene on chromosome 1q32.1, encoding Protein phosphatase 1 regulatory subunit 15B (Q5SWA1). Maintains low levels of EIF2S1 phosphorylation in unstressed cells by promoting its dephosphorylation by PP1. It is a selective cancer dependency (DepMap: 76.4% of cell lines).

This gene encodes a protein phosphatase I-interacting protein that promotes the dephosphorylation of eukaryotic translation initiation factor 2A to regulate translation under conditions of cellular stress. The transcribed messenger RNA contains two upstream open reading frames (ORFs) that repress translation of the main protein coding ORF under normal conditions, while the protein coding ORF is expressed at high levels in response to stress. Continual translation of the mRNA under conditions of eukaryotic translation initiation factor 2A inactivation is thought to create a feedback loop for reactivation of the gene during recovery from stress. In addition, it has been shown that this protein plays a role in membrane traffic that is independent of translation and that it is required for exocytosis from erythroleukemia cells. Allelic variants of this gene are associated with microcephaly, short stature, and impaired glucose metabolism.

Source: NCBI Gene 84919 — RefSeq curated summary.

At a glance

• Gene–disease (curated): microcephaly, short stature, and impaired glucose metabolism 2 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 233 total
• Phenotypes (HPO): 84
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 76.4% of screened cell lines
• MANE Select transcript: NM_032833

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14951
Approved symbol	PPP1R15B
Name	protein phosphatase 1 regulatory subunit 15B
Location	1q32.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ14744
Ensembl gene	ENSG00000158615
Ensembl biotype	protein_coding
OMIM	613257
Entrez	84919

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 2 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000367188, ENST00000687263, ENST00000689921, ENST00000690849, ENST00000693720

RefSeq mRNA: 1 — MANE Select: NM_032833 NM_032833

CCDS: CCDS1445

Canonical transcript exons

ENST00000367188 — 2 exons

Exon	Start	End
ENSE00001443770	204403381	204406313
ENSE00001443771	204409492	204411817

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 96.03.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 48.9266 / max 570.6916, expressed in 1820 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
16916	43.5265	1816
16919	2.5581	859
16917	1.3814	919
16918	0.9742	649
16910	0.4865	245

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	96.03	gold quality
kidney epithelium	UBERON:0004819	95.99	gold quality
cartilage tissue	UBERON:0002418	95.51	gold quality
bone marrow cell	CL:0002092	95.30	gold quality
epithelial cell of pancreas	CL:0000083	95.20	gold quality
parotid gland	UBERON:0001831	95.20	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.00	gold quality
lower lobe of lung	UBERON:0008949	94.85	gold quality
placenta	UBERON:0001987	94.71	gold quality
bone marrow	UBERON:0002371	94.26	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.90	gold quality
colonic mucosa	UBERON:0000317	93.80	gold quality
oocyte	CL:0000023	93.78	gold quality
cauda epididymis	UBERON:0004360	93.70	gold quality
tibialis anterior	UBERON:0001385	93.58	gold quality
vena cava	UBERON:0004087	93.11	gold quality
cardiac muscle of right atrium	UBERON:0003379	93.10	gold quality
epithelium of mammary gland	UBERON:0003244	92.96	gold quality
mammary duct	UBERON:0001765	92.92	gold quality
monocyte	CL:0000576	92.82	gold quality
leukocyte	CL:0000738	92.72	gold quality
bronchial epithelial cell	CL:0002328	92.52	gold quality
bronchus	UBERON:0002185	92.41	gold quality
gall bladder	UBERON:0002110	92.09	gold quality
oral cavity	UBERON:0000167	92.07	gold quality
jejunal mucosa	UBERON:0000399	91.85	gold quality
adrenal tissue	UBERON:0018303	91.78	gold quality
vermiform appendix	UBERON:0001154	91.70	gold quality
upper leg skin	UBERON:0004262	91.69	gold quality
cardia of stomach	UBERON:0001162	91.50	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	5.07
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF1, NFE2L2

miRNA regulators (miRDB)

201 targeting PPP1R15B, 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-3613-3P	100.00	76.36	7965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-196B-5P	100.00	68.16	681
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-3185	99.99	68.12	1959
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 76.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 9)

• the mammalian traffic machinery co-opts p-eIF2alpha and CReP, regulators of translation initiation. (PMID:22915583)
• CIP2A regulates cancer metabolism and CREB phosphorylation in non-small cell lung cancer (PMID:25325377)
• the first homozygous mutation in the PPP1R15B gene encoding the regulatory subunit of an eIF2alpha-specific phosphatase in two siblings affected by a novel syndrome of diabetes of youth with short stature, intellectual disability, and microcephaly (PMID:26159176)
• Whole-exome sequencing identified a homozygous missense mutation, c.1972G>A; p.Arg658Cys, in protein phosphatase 1, regulatory subunit 15b (PPP1R15B) (PMID:26307080)
• p97-mediated degradation, together with a reduction in CReP synthesis, is essential for timely stress-induced reduction of CReP levels and, consequently, for robust eIF2alpha phosphorylation to enforce the stress response. (PMID:29599191)
• Substrate recognition determinants of human eIF2alpha phosphatases. (PMID:34847777)
• An integrative pan-cancer analysis illustrating the key role of LRP11 in cervical cancer. (PMID:36930084)
• The PPP1R15 Family of eIF2-alpha Phosphatase Targeting Subunits (GADD34 and CReP). (PMID:38139150)
• Recruitment of trimeric eIF2 by phosphatase non-catalytic subunit PPP1R15B. (PMID:38159565)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ppp1r15b	ENSMUSG00000046062
rattus_norvegicus	Ppp1r15b	ENSRNOG00000028493
drosophila_melanogaster	PPP1R15	FBGN0034948

Paralogs (1): PPP1R15A (ENSG00000087074)

Protein

Protein identifiers

Protein phosphatase 1 regulatory subunit 15B — Q5SWA1 (reviewed: Q5SWA1)

All UniProt accessions (4): A0A8I5KSH1, A0A8I5KUJ3, A0A8I5KV52, Q5SWA1

UniProt curated annotations — full annotation on UniProt →

Function. Maintains low levels of EIF2S1 phosphorylation in unstressed cells by promoting its dephosphorylation by PP1.

Subunit / interactions. Part of a complex containing PPP1R15B, PP1 and NCK1/2. Interacts with PP1.

Disease relevance. Microcephaly, short stature, and impaired glucose metabolism 2 (MSSGM2) [MIM:616817] An autosomal recessive disease characterized by microcephaly, intellectual disability, short stature, and disturbed glucose metabolism. The disease is caused by variants affecting the gene represented in this entry. Defects in PPP1R15B has been found in a patient with isolated coloboma, a defect of the eye characterized by the absence of ocular structures due to abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). Isolated colobomas may be associated with an abnormally small eye (microphthalmia) or small cornea.

Miscellaneous. The phosphatase activity of the PPP1R15B-PP1 complex toward EIF2S1 is specifically inhibited by Salubrinal, a drug that protects cells from endoplasmic reticulum stress.

Similarity. Belongs to the PPP1R15 family.

RefSeq proteins (1): NP_116222* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019512	Prot_Pase1_reg-su15B_N	Domain
IPR019523	Prot_Pase1_reg-su15A/B_C	Domain
IPR051254	PPP1R15	Family

Pfam: PF10472, PF10488

UniProt features (24 total): sequence variant 7, region of interest 5, compositionally biased region 5, modified residue 3, sequence conflict 2, chain 1, strand 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
4V0W	X-RAY DIFFRACTION	1.55
4V0V	X-RAY DIFFRACTION	1.61
4V0X	X-RAY DIFFRACTION	1.85
9HVF	ELECTRON MICROSCOPY	3.8
4V0U	X-RAY DIFFRACTION	7.88

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5SWA1-F1	49.74	0.06

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (3): 203, 205, 508

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 466 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GSE45365_NK_CELL_VS_CD11B_DC_DN, GSE45365_NK_CELL_VS_BCELL_UP, GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, TGGTGCT_MIR29A_MIR29B_MIR29C, ACTACCT_MIR196A_MIR196B, TGCGCANK_UNKNOWN, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, YY1_Q6, GOBP_CELLULAR_RESPONSE_TO_TOPOLOGICALLY_INCORRECT_PROTEIN, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION

GO Biological Process (8): negative regulation of protein phosphorylation (GO:0001933), regulation of translation (GO:0006417), ER overload response (GO:0006983), response to endoplasmic reticulum stress (GO:0034976), response to hydrogen peroxide (GO:0042542), negative regulation of PERK-mediated unfolded protein response (GO:1903898), response to oxidative stress (GO:0006979), regulation of protein metabolic process (GO:0051246)

GO Molecular Function (5): protein phosphatase 1 binding (GO:0008157), protein phosphatase regulator activity (GO:0019888), molecular adaptor activity (GO:0060090), eukaryotic initiation factor eIF2 binding (GO:0071074), protein binding (GO:0005515)

GO Cellular Component (2): protein phosphatase type 1 complex (GO:0000164), endoplasmic reticulum (GO:0005783)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein phosphatase binding	2
binding	2
cytoplasm	2
regulation of protein phosphorylation	1
protein phosphorylation	1
negative regulation of protein modification process	1
negative regulation of phosphorylation	1
translation	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
ER-nucleus signaling pathway	1
response to endoplasmic reticulum stress	1
cellular response to biotic stimulus	1
cellular response to stress	1
response to reactive oxygen species	1
PERK-mediated unfolded protein response	1
negative regulation of endoplasmic reticulum unfolded protein response	1
regulation of PERK-mediated unfolded protein response	1
response to stress	1
protein metabolic process	1
regulation of macromolecule metabolic process	1
regulation of primary metabolic process	1
phosphoprotein phosphatase activity	1
phosphatase regulator activity	1
molecular_function	1
translation initiation factor binding	1
protein serine/threonine phosphatase complex	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

870 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPP1R15B	PPP1CC	P36873	931
PPP1R15B	PPP1CB	P37140	931
PPP1R15B	EIF2S1	P05198	874
PPP1R15B	EIF1	P41567	794
PPP1R15B	NRF1	Q16656	717
PPP1R15B	EIF2AK3	Q9NZJ5	715
PPP1R15B	EIF2S2	P20042	630
PPP1R15B	EIF2S3	P41091	629
PPP1R15B	PPP1R15A	O75807	612
PPP1R15B	EIF2AK4	Q9P2K8	544
PPP1R15B	PPP1CA	P08129	536
PPP1R15B	PPM1G	O15355	516
PPP1R15B	GOLT1A	Q6ZVE7	420
PPP1R15B	ATF6	P18850	419
PPP1R15B	ATF4	P18848	412

IntAct

90 interactions, top by confidence:

A	B	Type	Score
PPP1R15B	PPP1CA	psi-mi:“MI:0915”(physical association)	0.770
PPP1CA	PPP1R15B	psi-mi:“MI:0915”(physical association)	0.770
PPP1CC	CCDC85C	psi-mi:“MI:0914”(association)	0.740
PPP1CC	CCDC85C	psi-mi:“MI:2364”(proximity)	0.740
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
PPP1R15B	PPP1CC	psi-mi:“MI:0915”(physical association)	0.690
PPP1CA	CCDC85C	psi-mi:“MI:0914”(association)	0.670
PPP1CA	CCDC85C	psi-mi:“MI:2364”(proximity)	0.670
TRIM23	PPP1R15B	psi-mi:“MI:0915”(physical association)	0.560
PPP1R15B	PPP1CC	psi-mi:“MI:0915”(physical association)	0.550
FSHR	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
ZNRF4	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
PTGER3	PIK3R2	psi-mi:“MI:0914”(association)	0.530
TCIRG1	AP3D1	psi-mi:“MI:0914”(association)	0.530
CHRNA9	CHEK1	psi-mi:“MI:0914”(association)	0.530
ANO4	ANO6	psi-mi:“MI:0914”(association)	0.530
ABCB5	PPP1R15B	psi-mi:“MI:0915”(physical association)	0.400
	PPP1R15B	psi-mi:“MI:0915”(physical association)	0.400
PPP1R15B	PPP1CC	psi-mi:“MI:0915”(physical association)	0.370
PPP1CC	PPP1R15B	psi-mi:“MI:0915”(physical association)	0.370
Ppp1cb	MYO1C	psi-mi:“MI:0914”(association)	0.350
PPP1CB	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
CHRNA9	TMEM120B	psi-mi:“MI:0914”(association)	0.350

ESM2 similar proteins: A0P8Z5, B0KYV5, B1WC58, B2RYR0, F1LR10, F6SNN2, O75128, O75410, P51826, P61590, P61591, P61592, P61593, P61594, Q3USH1, Q501R9, Q5IFK1, Q5PQK4, Q5R8C5, Q5SU73, Q5SWA1, Q5U5Q9, Q6NZF1, Q6P1D7, Q6P7W0, Q6PJW8, Q6Y685, Q6ZSG2, Q6ZVT6, Q7TT79, Q80XI1, Q80XJ2, Q80YR6, Q86T90, Q8BFU3, Q8C9B9, Q8IY92, Q8IYW5, Q8ND24, Q8NEM0

Diamond homologs: O75807, P08353, P17564, P28283, P36313, P37318, P37319, Q2KI51, Q5SWA1, Q60465, Q6IN02, Q8BFW3, Q65212

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 106 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Transport of small molecules	12	4.3×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
long-chain fatty acid metabolic process	5	31.8×	1e-04
sodium ion import across plasma membrane	5	31.8×	1e-04
monoatomic ion transport	6	9.6×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	166
Likely benign	49
Benign	8

Top pathogenic / likely-pathogenic (0)

SpliceAI

488 predictions. Top by Δscore:

Variant	Effect	Δscore
1:204406312:ACCTA:A	acceptor_loss	1.0000
1:204406313:CCT:C	acceptor_loss	1.0000
1:204406314:CTACA:C	acceptor_loss	1.0000
1:204406309:GTTAC:G	acceptor_gain	0.9900
1:204406310:TTAC:T	acceptor_gain	0.9900
1:204406311:TAC:T	acceptor_gain	0.9900
1:204406314:C:CC	acceptor_gain	0.9900
1:204406315:T:A	acceptor_loss	0.9900
1:204409487:CAAA:C	donor_loss	0.9900
1:204409488:AAACC:A	donor_loss	0.9900
1:204409489:AACCT:A	donor_loss	0.9900
1:204409490:A:AT	donor_loss	0.9900
1:204409519:T:TA	donor_gain	0.9900
1:204406312:AC:A	acceptor_gain	0.9800
1:204406313:CC:C	acceptor_gain	0.9800
1:204409831:T:TA	donor_gain	0.9800
1:204406317:C:CT	acceptor_gain	0.9700
1:204409864:G:A	donor_gain	0.9600
1:204405255:A:AC	acceptor_gain	0.9400
1:204406318:A:T	acceptor_gain	0.9400
1:204409729:A:AC	donor_gain	0.9200
1:204406195:T:TA	donor_gain	0.8800
1:204409490:A:AC	donor_gain	0.8700
1:204409491:C:CC	donor_gain	0.8700
1:204409501:TTTG:T	donor_gain	0.8700
1:204409793:T:TA	donor_gain	0.8500
1:204406113:AAGT:A	donor_gain	0.8300
1:204408181:C:A	donor_gain	0.8300
1:204410202:C:CT	donor_gain	0.8300
1:204410203:T:TT	donor_gain	0.8300

AlphaMissense

4663 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:204406219:A:G	F672S	0.998
1:204406250:A:G	W662R	0.998
1:204406250:A:T	W662R	0.998
1:204406210:C:G	R675P	0.997
1:204406218:G:C	F672L	0.997
1:204406218:G:T	F672L	0.997
1:204406220:A:G	F672L	0.997
1:204406248:C:A	W662C	0.997
1:204406248:C:G	W662C	0.997
1:204406158:T:A	R692S	0.995
1:204406158:T:G	R692S	0.995
1:204406190:C:G	A682P	0.995
1:204406219:A:C	F672C	0.995
1:204406222:C:A	R671M	0.995
1:204406262:G:T	R658S	0.995
1:204406305:G:C	F643L	0.995
1:204406305:G:T	F643L	0.995
1:204406307:A:G	F643L	0.995
1:204409936:A:C	F492L	0.995
1:204409936:A:T	F492L	0.995
1:204409938:A:G	F492L	0.995
1:204406186:A:T	I683N	0.994
1:204406221:C:A	R671S	0.994
1:204406221:C:G	R671S	0.994
1:204406222:C:G	R671T	0.994
1:204410440:G:C	S324R	0.994
1:204410440:G:T	S324R	0.994
1:204410442:T:G	S324R	0.994
1:204406233:C:A	R667S	0.993
1:204406233:C:G	R667S	0.993

dbSNP variants (sampled 300 via entrez): RS1000234329 (1:204397806 G>A), RS1000404123 (1:204409305 G>C), RS1000469019 (1:204403786 A>G), RS1000774310 (1:204402824 A>T), RS1000888201 (1:204398228 G>A), RS1000908463 (1:204409100 C>T), RS1001256710 (1:204398078 C>T), RS1001296946 (1:204407391 T>C), RS1001411369 (1:204413271 C>G), RS1001622830 (1:204409630 G>A), RS1001630182 (1:204407714 T>C), RS1001757667 (1:204412996 G>T), RS1002053602 (1:204409921 C>G), RS1002124019 (1:204397277 C>G), RS1002716946 (1:204398625 T>C)

Disease associations

OMIM: gene MIM:613257 | disease phenotypes: MIM:616817

GenCC curated gene-disease

Disease	Classification	Inheritance
microcephaly, short stature, and impaired glucose metabolism 2	Strong	Autosomal recessive
primary microcephaly-mild intellectual disability-young-onset diabetes syndrome	Supportive	Autosomal recessive

Mondo (2): microcephaly, short stature, and impaired glucose metabolism 2 (MONDO:0014785), primary microcephaly-mild intellectual disability-young-onset diabetes syndrome (MONDO:0018320)

Orphanet (1): Primary microcephaly-mild intellectual disability-young-onset diabetes syndrome (Orphanet:391408)

HPO phenotypes

84 total (30 of 84 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000089	Renal hypoplasia
HP:0000160	Narrow mouth
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000274	Small face
HP:0000275	Narrow face
HP:0000286	Epicanthus
HP:0000293	Full cheeks
HP:0000294	Low anterior hairline
HP:0000311	Round face
HP:0000322	Short philtrum
HP:0000341	Narrow forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000400	Macrotia
HP:0000407	Sensorineural hearing impairment
HP:0000445	Wide nose
HP:0000463	Anteverted nares
HP:0000470	Short neck
HP:0000494	Downslanted palpebral fissures
HP:0000592	Blue sclerae
HP:0000601	Hypotelorism
HP:0000664	Synophrys
HP:0000677	Oligodontia
HP:0000685	Hypoplasia of teeth
HP:0000767	Pectus excavatum
HP:0000819	Diabetes mellitus

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001942_20	Prostate cancer	2.000000e-11
GCST006922_4	Regular attendance at a religious group	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009592	social interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4630830 (SINGLE PROTEIN)

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

ChEMBL bioactivities

1 potent at pChembl≥5 of 1 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.48	IC50	33	nM	CHEMBL2369159

PubChem BioAssay actives

1 with measured affinity, of 1 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(E)-(2,3-dichlorophenyl)methylideneamino]guanidine	1668282: Inhibition of amino-terminal MBP-tagged/carboxy-terminal His6-tagged human PPP1R15B (325 to 626 residues)	ic50	0.0330	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, affects expression, increases abundance	2
Valproic Acid	affects expression, decreases methylation, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
bisphenol A	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
methylparaben	increases expression	1
afimoxifene	affects response to substance	1
sodium arsenite	increases expression	1
coumarin	increases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-nonanoic acid	increases expression	1
abrine	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
jinfukang	decreases expression	1
Sunitinib	increases expression	1
Leflunomide	increases expression	1
Benzo(a)pyrene	increases expression	1
Doxorubicin	increases expression	1
Formaldehyde	decreases expression	1
Ozone	affects expression, increases abundance	1
Phenobarbital	affects expression	1
Silver	increases expression	1
Smoke	decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
Urethane	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Josamycin	affects response to substance	1
Cyclosporine	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4629320	Binding	Inhibition of amino-terminal MBP-tagged/carboxy-terminal His6-tagged human PPP1R15B (325 to 626 residues)	Monovalent protein-degraders - Insights and future perspectives. — Bioorg Med Chem Lett

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2BU	Abcam HeLa PPP1R15B KO	Cancer cell line	Female

Clinical trials (associated diseases)

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