PPP6R3

Summary

PPP6R3 (protein phosphatase 6 regulatory subunit 3, HGNC:1173) is a protein-coding gene on chromosome 11q13, encoding Serine/threonine-protein phosphatase 6 regulatory subunit 3 (Q5H9R7). Regulatory subunit of protein phosphatase 6 (PP6). It is a selective cancer dependency (DepMap: 23.8% of cell lines).

Protein phosphatase regulatory subunits, such as SAPS3, modulate the activity of protein phosphatase catalytic subunits by restricting substrate specificity, recruiting substrates, and determining the intracellular localization of the holoenzyme. SAPS3 is a regulatory subunit for the protein phosphatase-6 catalytic subunit (PPP6C; MIM 612725) (Stefansson and Brautigan, 2006 [PubMed 16769727]).

Source: NCBI Gene 55291 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 127 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 23.8% of screened cell lines
• MANE Select transcript: NM_001164161

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1173
Approved symbol	PPP6R3
Name	protein phosphatase 6 regulatory subunit 3
Location	11q13
Locus type	gene with protein product
Status	Approved
Aliases	SAPLa, DKFZp781E2374, DKFZp781O2362, DKFZp781E17107, SAP190, SAPL, PP6R3, FLJ11058, FLJ43065, KIAA1558, MGC125711, MGC125712
Ensembl gene	ENSG00000110075
Ensembl biotype	protein_coding
OMIM	610879
Entrez	55291

Gene structure

Transcript identifiers

Ensembl transcripts: 130 — 120 protein_coding, 7 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000265636, ENST00000265637, ENST00000393800, ENST00000393801, ENST00000524845, ENST00000524904, ENST00000525050, ENST00000525152, ENST00000525421, ENST00000526307, ENST00000526574, ENST00000526593, ENST00000527069, ENST00000527403, ENST00000528635, ENST00000529172, ENST00000529344, ENST00000529710, ENST00000529907, ENST00000530427, ENST00000530734, ENST00000531244, ENST00000531432, ENST00000533127, ENST00000534190, ENST00000534534, ENST00000871852, ENST00000871853, ENST00000871854, ENST00000871855, ENST00000871856, ENST00000871857, ENST00000871858, ENST00000871859, ENST00000871860, ENST00000871861, ENST00000871862, ENST00000871863, ENST00000871864, ENST00000871865, ENST00000871866, ENST00000871867, ENST00000871868, ENST00000871869, ENST00000871870, ENST00000871871, ENST00000871872, ENST00000871873, ENST00000871874, ENST00000871875, ENST00000871876, ENST00000871877, ENST00000871878, ENST00000871879, ENST00000871880, ENST00000871881, ENST00000929857, ENST00000929858, ENST00000929859, ENST00000929860, ENST00000929861, ENST00000929862, ENST00000929863, ENST00000929864, ENST00000929865, ENST00000929866, ENST00000929867, ENST00000929868, ENST00000929869, ENST00000929870, ENST00000929871, ENST00000929872, ENST00000929873, ENST00000929874, ENST00000929875, ENST00000929876, ENST00000929877, ENST00000929878, ENST00000929879, ENST00000929880, ENST00000929881, ENST00000929882, ENST00000929883, ENST00000929884, ENST00000929885, ENST00000929886, ENST00000929887, ENST00000929888, ENST00000929889, ENST00000929890, ENST00000929891, ENST00000929892, ENST00000929893, ENST00000929894, ENST00000929895, ENST00000929896, ENST00000929897, ENST00000929898, ENST00000929899, ENST00000929900, ENST00000929901, ENST00000929902, ENST00000929903, ENST00000929904, ENST00000929905, ENST00000929906, ENST00000929907, ENST00000929908, ENST00000953359, ENST00000953360, ENST00000953361, ENST00000953362, ENST00000953363, ENST00000953364, ENST00000953365, ENST00000953366, ENST00000953367, ENST00000953368, ENST00000953369, ENST00000953370, ENST00000953371, ENST00000953372, ENST00000953373, ENST00000953374, ENST00000953375, ENST00000953376, ENST00000953377, ENST00000953378, ENST00000953379, ENST00000953380

RefSeq mRNA: 39 — MANE Select: NM_001164161 NM_001164160, NM_001164161, NM_001164162, NM_001164163, NM_001164164, NM_001352347, NM_001352348, NM_001352350, NM_001352351, NM_001352352, NM_001352353, NM_001352354, NM_001352355, NM_001352356, NM_001352357, NM_001352358, NM_001352359, NM_001352360, NM_001352361, NM_001352362, NM_001352363, NM_001352364, NM_001352365, NM_001352366, NM_001352368, NM_001352369, NM_001352370, NM_001352371, NM_001352372, NM_001352373, NM_001352374, NM_001352375, NM_001352376, NM_001352377, NM_001352378, NM_001352379, NM_001352380, NM_001411030, NM_018312

CCDS: CCDS53671, CCDS53672, CCDS53673, CCDS53674, CCDS53675, CCDS8182, CCDS91521

Canonical transcript exons

ENST00000393800 — 24 exons

Exon	Start	End
ENSE00000824106	68571040	68571104
ENSE00000824107	68574109	68574224
ENSE00000824110	68575958	68576043
ENSE00000904476	68587927	68588024
ENSE00000992117	68551121	68551186
ENSE00000992118	68554145	68554257
ENSE00001200706	68564303	68564432
ENSE00001200708	68558566	68558679
ENSE00001378469	68519501	68519651
ENSE00001424192	68460752	68460827
ENSE00001516530	68583043	68583129
ENSE00002172164	68613066	68615334
ENSE00003469412	68601863	68601969
ENSE00003477869	68603342	68603492
ENSE00003478740	68569748	68569897
ENSE00003485967	68590660	68590714
ENSE00003511089	68548067	68548204
ENSE00003577137	68567014	68567166
ENSE00003579879	68600341	68600494
ENSE00003606346	68544838	68545024
ENSE00003651615	68591576	68591706
ENSE00003663547	68609904	68610023
ENSE00003693862	68596097	68596218
ENSE00003792120	68537659	68537891

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 98.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 74.9945 / max 1124.8753, expressed in 1823 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115540	74.9945	1823

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	98.06	gold quality
adrenal tissue	UBERON:0018303	97.84	gold quality
sural nerve	UBERON:0015488	97.60	gold quality
buccal mucosa cell	CL:0002336	97.49	gold quality
colonic epithelium	UBERON:0000397	97.30	gold quality
tendon	UBERON:0000043	96.56	gold quality
right lobe of thyroid gland	UBERON:0001119	96.48	gold quality
left lobe of thyroid gland	UBERON:0001120	96.15	gold quality
thyroid gland	UBERON:0002046	96.05	gold quality
left ovary	UBERON:0002119	95.75	gold quality
mucosa of stomach	UBERON:0001199	95.59	gold quality
right ovary	UBERON:0002118	95.48	gold quality
ovary	UBERON:0000992	95.22	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	95.18	gold quality
body of uterus	UBERON:0009853	95.06	gold quality
ventricular zone	UBERON:0003053	95.02	gold quality
right uterine tube	UBERON:0001302	95.00	gold quality
endocervix	UBERON:0000458	94.87	gold quality
vagina	UBERON:0000996	94.76	gold quality
ectocervix	UBERON:0012249	94.72	gold quality
gastrocnemius	UBERON:0001388	94.67	gold quality
right lung	UBERON:0002167	94.64	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.59	gold quality
tibial nerve	UBERON:0001323	94.54	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.53	gold quality
muscle of leg	UBERON:0001383	94.45	gold quality
rectum	UBERON:0001052	94.44	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.38	gold quality
lower esophagus	UBERON:0013473	94.37	gold quality
skin of leg	UBERON:0001511	94.35	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.86

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

140 targeting PPP6R3, 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-3646	100.00	73.56	5283
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-570-3P	99.96	72.41	4910
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-106A-5P	99.90	73.94	2683

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 23.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 4)

• Results from a study on gene expression variability markers in early-stage human embryos shows that PPP6R3 is a putative expression variability marker for the 3-day, 8-cell embryo stage. (PMID:26288249)
• Molecular analyses revealed the presence and amplification of the novel PPPR6-USP6 gene fusion, which resulted in USP6 mRNA transcriptional upregulation. These findings further support the oncogenic role of the USP6 protease in mesenchymal neoplasia and expand the biologic potential of Nodular fasciitis (PMID:27113271)
• we found a DPP9-PPP6R3 fusion transcript in one tumor showing a matching genomic 11;19-translocation. Another tumor had a rearrangement of DPP9 with PLIN3. Both rearrangements were associated with diminished expression of the 3’ end of DPP9 corresponding to the breakpoints identified by RNA-seq. (PMID:28893231)
• The substitution of Ala in nine putative phosphorylation sites in SAPS3 was required to prevent CK2 activation of the phosphatase. Different CK2 chemical inhibitors equally increased phosphorylation of endogenous AURKA in living cells, consistent with reduction in PP6 activity. (PMID:31904830)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ppp6r3	ENSDARG00000013379
mus_musculus	Ppp6r3	ENSMUSG00000024908
rattus_norvegicus	Ppp6r3	ENSRNOG00000015540
drosophila_melanogaster	fmt	FBGN0035688
caenorhabditis_elegans		WBGENE00008166

Paralogs (2): PPP6R2 (ENSG00000100239), PPP6R1 (ENSG00000105063)

Protein

Protein identifiers

Serine/threonine-protein phosphatase 6 regulatory subunit 3 — Q5H9R7 (reviewed: Q5H9R7)

Alternative names: SAPS domain family member 3, Sporulation-induced transcript 4-associated protein SAPL

All UniProt accessions (13): Q5H9R7, A0A1D5RMU2, E9PJD8, E9PK08, E9PKF6, E9PKG4, E9PNN8, E9PQP7, H0YDK9, H0YDW1, H0YEN2, H0YEV0, H7BXH2

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory subunit of protein phosphatase 6 (PP6). May function as a scaffolding PP6 subunit. May have an important role in maintaining immune self-tolerance.

Subunit / interactions. Protein phosphatase 6 (PP6) holoenzyme is proposed to be a heterotrimeric complex formed by the catalytic subunit, a SAPS domain-containing subunit (PP6R) and an ankyrin repeat-domain containing regulatory subunit (ARS). Interacts with PPP6C and ANKRD28.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Expressed in skeletal muscle, placenta, heart, pancreas, testis, brain, lung, liver, kidney, spleen, thymus, prostate, small intestine, colon and leukocytes.

Similarity. Belongs to the SAPS family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q5H9R7-1	1	yes
Q5H9R7-2	2
Q5H9R7-3	3, B, C11orf23b, SAPLb
Q5H9R7-4	4, A, C11orf23a, SAPLa
Q5H9R7-5	5
Q5H9R7-6	6

RefSeq proteins (39): NP_001157632, NP_001157633, NP_001157634, NP_001157635, NP_001157636, NP_001339276, NP_001339277, NP_001339279, NP_001339280, NP_001339281, NP_001339282, NP_001339283, NP_001339284, NP_001339285, NP_001339286, NP_001339287, NP_001339288, NP_001339289, NP_001339290, NP_001339291, NP_001339292, NP_001339293, NP_001339294, NP_001339295, NP_001339297, NP_001339298, NP_001339299, NP_001339300, NP_001339301, NP_001339302, NP_001339303, NP_001339304, NP_001339305, NP_001339306, NP_001339307, NP_001339308, NP_001339309, NP_001397959, NP_060782 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007587	SAPS	Family
IPR016024	ARM-type_fold	Homologous_superfamily

Pfam: PF04499

UniProt features (22 total): modified residue 7, splice variant 5, sequence conflict 4, compositionally biased region 3, chain 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5H9R7-F1	68.31	0.44

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 (7): 722, 853, 315, 579, 617, 631, 634

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-171319	Telomere Extension By Telomerase
R-HSA-204005	COPII-mediated vesicle transport

MSigDB gene sets: 196 (showing top): TAATAAT_MIR126, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, TGCACTT_MIR519C_MIR519B_MIR519A, AAGCCAT_MIR135A_MIR135B, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, REACTOME_MEMBRANE_TRAFFICKING, ACTGCAG_MIR173P, chr11q13, MCBRYAN_PUBERTAL_BREAST_4_5WK_DN, CCTGTGA_MIR513, REACTOME_EXTENSION_OF_TELOMERES, NIKOLSKY_BREAST_CANCER_11Q12_Q14_AMPLICON, HAND1E47_01, TGCCTTA_MIR124A, MILI_PSEUDOPODIA_CHEMOTAXIS_DN

GO Biological Process (2): regulation of signal transduction (GO:0009966), glycoprotein catabolic process (GO:0006516)

GO Molecular Function (3): protein phosphatase regulator activity (GO:0019888), protein phosphatase binding (GO:0019903), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), plasma membrane (GO:0005886), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Extension of Telomeres	1
ER to Golgi Anterograde Transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
signal transduction	1
regulation of cell communication	1
regulation of signaling	1
regulation of response to stimulus	1
glycoprotein metabolic process	1
protein catabolic process	1
carbohydrate derivative catabolic process	1
phosphoprotein phosphatase activity	1
phosphatase regulator activity	1
protein phosphatase binding	1
phosphatase binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
membrane	1
cell periphery	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1282 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPP6R3	PPP6C	O00743	971
PPP6R3	SF3B1	O75533	882
PPP6R3	PPP2CA	P05323	754
PPP6R3	ANKRD28	O15084	751
PPP6R3	NFKBIE	O00221	706
PPP6R3	ANKRD44	Q8N8A2	695
PPP6R3	DPH3	Q96FX2	657
PPP6R3	KTI12	Q96EK9	613
PPP6R3	ANKRD52	Q8NB46	591
PPP6R3	PPP4C	P33172	561
PPP6R3	ELP6	Q0PNE2	529
PPP6R3	PRKDC	P78527	520
PPP6R3	PPP6R2	O75170	502
PPP6R3	PPP6R1	Q9UPN7	485
PPP6R3	CPED1	A4D0V7	447

IntAct

173 interactions, top by confidence:

A	B	Type	Score
PPP6R1	PPP6C	psi-mi:“MI:0914”(association)	0.920
PPP6C	ANKRD28	psi-mi:“MI:0914”(association)	0.870
ANKRD28	PPP6C	psi-mi:“MI:0914”(association)	0.870
PPP6R3	PPP6C	psi-mi:“MI:0915”(physical association)	0.800
ANKRD52	PPP6C	psi-mi:“MI:0914”(association)	0.790
ANKRD44	PPP6C	psi-mi:“MI:0914”(association)	0.790
ANKRD28	PPP6R3	psi-mi:“MI:0915”(physical association)	0.710
PPP6R3	ANKRD28	psi-mi:“MI:0915”(physical association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
ANKRD44	ANKRD28	psi-mi:“MI:0914”(association)	0.710
MOB1B	STK4	psi-mi:“MI:0914”(association)	0.630
Sh2d5	BCR	psi-mi:“MI:0914”(association)	0.580
PLK1	C1orf226	psi-mi:“MI:0914”(association)	0.560
MLF1	HAX1	psi-mi:“MI:0914”(association)	0.560
ARRDC4	WWP2	psi-mi:“MI:0914”(association)	0.530

BioGRID (333): PPP6R3 (Affinity Capture-MS), PPP6R3 (Affinity Capture-MS), PPP6R3 (Affinity Capture-MS), PPP6R3 (Affinity Capture-MS), PPP6R3 (Affinity Capture-MS), PPP6R3 (Affinity Capture-MS), PPP6R3 (Affinity Capture-RNA), DIEXF (Co-fractionation), NSUN5 (Co-fractionation), PPP6C (Co-fractionation), PPP6R3 (Co-fractionation), TIPRL (Co-fractionation), PPP6R3 (Affinity Capture-MS), PPP6R3 (Proximity Label-MS), PPP6R3 (Proximity Label-MS)

ESM2 similar proteins: A0A286Y9D1, A1L162, A1Z1Q3, A2VCV0, A6QQ66, A8KBE0, A8MQG7, B3NLX1, B4F6Q9, B4GT53, B4P6W7, O75496, O88513, O94880, P32447, P51860, Q02508, Q12373, Q16RY9, Q2T9W9, Q2TBJ0, Q3UYG8, Q4VA55, Q504Y3, Q5F471, Q5H9R7, Q5ZMS4, Q65Z40, Q66H73, Q6CN69, Q6DD45, Q6PAV8, Q6PG04, Q794H2, Q7Z5K2, Q8INT5, Q8LF97, Q8N4S0, Q8NI08, Q8VDY9

Diamond homologs: B5VMH6, C8ZCJ2, O74511, P36123, P40856, P43612, P53036, Q5H9R7, Q6NRF1, Q6NRI0, Q922D4, O75170, Q5F471, Q7TSI3, Q8R3Q2, Q9UPN7

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 158 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.

GO biological processes:

GO term	Partners	Fold	FDR
canonical Wnt signaling pathway	10	11.7×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	95
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

5383 predictions. Top by Δscore:

Variant	Effect	Δscore
11:68537892:G:GG	donor_gain	1.0000
11:68544989:GTGC:G	donor_gain	1.0000
11:68544990:TGCT:T	donor_gain	1.0000
11:68544991:GCTA:G	donor_gain	1.0000
11:68548062:TCTA:T	acceptor_loss	1.0000
11:68548064:TA:T	acceptor_loss	1.0000
11:68548065:A:AG	acceptor_gain	1.0000
11:68548066:G:GA	acceptor_gain	1.0000
11:68548066:GATT:G	acceptor_gain	1.0000
11:68548201:GAAT:G	donor_gain	1.0000
11:68548203:ATGT:A	donor_loss	1.0000
11:68548204:TGTGA:T	donor_loss	1.0000
11:68548205:G:GG	donor_gain	1.0000
11:68548207:GAGTA:G	donor_loss	1.0000
11:68548208:AGTAG:A	donor_loss	1.0000
11:68551119:A:AG	acceptor_gain	1.0000
11:68551119:AGT:A	acceptor_gain	1.0000
11:68551120:G:GA	acceptor_gain	1.0000
11:68551120:GT:G	acceptor_gain	1.0000
11:68551120:GTG:G	acceptor_gain	1.0000
11:68551184:GAT:G	donor_gain	1.0000
11:68551187:G:GG	donor_gain	1.0000
11:68554253:GAAAA:G	donor_gain	1.0000
11:68554258:G:GG	donor_gain	1.0000
11:68558680:G:GG	donor_gain	1.0000
11:68564300:A:AG	acceptor_gain	1.0000
11:68564301:A:G	acceptor_gain	1.0000
11:68569747:GA:G	acceptor_gain	1.0000
11:68569747:GAA:G	acceptor_gain	1.0000
11:68569747:GAAC:G	acceptor_gain	1.0000

AlphaMissense

5855 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:68537668:T:C	F2L	1.000
11:68537669:T:C	F2S	1.000
11:68537669:T:G	F2C	1.000
11:68537670:T:A	F2L	1.000
11:68537670:T:G	F2L	1.000
11:68537671:T:A	W3R	1.000
11:68537671:T:C	W3R	1.000
11:68537673:G:C	W3C	1.000
11:68537673:G:T	W3C	1.000
11:68537677:T:C	F5L	1.000
11:68537679:T:A	F5L	1.000
11:68537679:T:G	F5L	1.000
11:68537714:T:C	L17P	1.000
11:68537762:T:A	V33D	1.000
11:68537778:A:C	K38N	1.000
11:68537778:A:T	K38N	1.000
11:68537795:T:C	L44P	1.000
11:68544855:G:A	C82Y	1.000
11:68544856:T:G	C82W	1.000
11:68544864:T:A	L85H	1.000
11:68544864:T:C	L85P	1.000
11:68544966:T:A	L119Q	1.000
11:68544966:T:C	L119P	1.000
11:68544972:C:A	A121D	1.000
11:68544974:A:C	S122R	1.000
11:68544976:T:A	S122R	1.000
11:68544976:T:G	S122R	1.000
11:68544977:T:C	F123L	1.000
11:68544979:C:A	F123L	1.000
11:68544979:C:G	F123L	1.000

dbSNP variants (sampled 300 via entrez): RS1000021834 (11:68534939 T>C), RS1000077621 (11:68550152 A>G), RS1000105632 (11:68575340 C>G), RS1000105721 (11:68463911 G>A), RS1000110851 (11:68590570 A>C,T), RS1000121029 (11:68581713 C>T), RS1000138455 (11:68493984 T>A,G), RS1000147325 (11:68574839 T>G), RS1000151068 (11:68470688 G>A), RS1000203723 (11:68533523 G>A), RS1000211227 (11:68500882 A>G), RS1000234498 (11:68581392 G>A), RS1000237112 (11:68483034 G>C,T), RS1000238492 (11:68610674 A>T), RS1000247162 (11:68609344 G>A,C)

Disease associations

OMIM: gene MIM:610879 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST002493_10	Bone mineral density (paediatric, skull)	2.000000e-10
GCST002493_9	Bone mineral density (paediatric, skull)	1.000000e-10
GCST003996_21	Monobrow	2.000000e-09
GCST004772_7	Bone mineral density (paediatric, total body less head)	1.000000e-09
GCST005171_5	QT interval	2.000000e-06
GCST006980_10	Fracture	8.000000e-44
GCST007641_1	Femoral neck section modulus	4.000000e-11
GCST010989_28	Body size at age 10	3.000000e-14
GCST012020_221	Serum metabolite levels	2.000000e-14
GCST90002390_37	Mean corpuscular hemoglobin	2.000000e-13
GCST90002392_353	Mean corpuscular volume	1.000000e-15

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007906	synophrys measurement
EFO:0004682	QT interval
EFO:0004511	femoral neck bone geometry
EFO:0009819	comparative body size at age 10, self-reported
EFO:0004527	mean corpuscular hemoglobin

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105773 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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
6.01	IC50	980	nM	MOLIBRESIB

PubChem BioAssay actives

1 with measured affinity, of 8 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-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179048: Inhibition of SAPS3 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.9800	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
2,4,6-tribromophenol	increases expression	1
methylmercuric chloride	decreases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	decreases expression	1
sodium arsenate	decreases expression	1
decabromobiphenyl ether	increases expression	1
beta-lapachone	decreases expression, increases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	increases abundance, affects cotreatment, decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
coumarin	decreases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
Temozolomide	decreases expression	1
Acetaminophen	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	decreases methylation	1
Caffeine	affects phosphorylation	1
Carbamazepine	affects expression	1
Doxorubicin	decreases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4012575	Binding	Binding affinity to serine/threonine-protein phosphatase 6 regulatory subunit 3 in human INA-6 cells after 3 hrs by nanoLC-MS/MS method	Ugi Reaction-Derived α-Acyl Aminocarboxamides Bind to Phosphatidylinositol 3-Kinase-Related Kinases, Inhibit HSF1-Dependent Heat Shock Response, and Induce Apoptosis in Multiple Myeloma Cells. — J Med Chem

Clinical trials (associated diseases)

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