PSMD9

Summary

PSMD9 (proteasome 26S subunit, non-ATPase 9, HGNC:9567) is a protein-coding gene on chromosome 12q24.31, encoding 26S proteasome non-ATPase regulatory subunit 9 (O00233). Acts as a chaperone during the assembly of the 26S proteasome, specifically of the base subcomplex of the PA700/19S regulatory complex (RC).

The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a non-ATPase subunit of the 19S regulator. Three transcript variants encoding two different isoforms have been found for this gene.

Source: NCBI Gene 5715 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 54 total
• Druggable target: yes
• MANE Select transcript: NM_002813

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9567
Approved symbol	PSMD9
Name	proteasome 26S subunit, non-ATPase 9
Location	12q24.31
Locus type	gene with protein product
Status	Approved
Aliases	p27, Rpn4
Ensembl gene	ENSG00000110801
Ensembl biotype	protein_coding
OMIM	603146
Entrez	5715

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 19 protein_coding, 4 nonsense_mediated_decay, 3 retained_intron

ENST00000261817, ENST00000361485, ENST00000535293, ENST00000537407, ENST00000538613, ENST00000540962, ENST00000541212, ENST00000542602, ENST00000543699, ENST00000544254, ENST00000544724, ENST00000858882, ENST00000858883, ENST00000858884, ENST00000858885, ENST00000858886, ENST00000858887, ENST00000922351, ENST00000922352, ENST00000922353, ENST00000922354, ENST00000922355, ENST00000922356, ENST00000922357, ENST00000970344, ENST00000970345

RefSeq mRNA: 2 — MANE Select: NM_002813 NM_001261400, NM_002813

CCDS: CCDS58284, CCDS9225

Canonical transcript exons

ENST00000541212 — 6 exons

Exon	Start	End
ENSE00001190529	121899634	121899845
ENSE00002278116	121888790	121888994
ENSE00002284064	121916284	121918297
ENSE00003590737	121894739	121894841
ENSE00003705205	121915856	121915944
ENSE00003707630	121903006	121903107

Expression profiles

Bgee: expression breadth ubiquitous, 182 present calls, max score 95.02.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 48.6457 / max 265.0884, expressed in 1827 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
128475	47.1325	1826
128474	1.5132	1101

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	95.02	gold quality
monocyte	CL:0000576	94.88	gold quality
granulocyte	CL:0000094	94.49	gold quality
mononuclear cell	CL:0000842	94.47	gold quality
leukocyte	CL:0000738	94.37	gold quality
body of pancreas	UBERON:0001150	94.25	gold quality
mucosa of transverse colon	UBERON:0004991	93.98	gold quality
body of stomach	UBERON:0001161	93.72	gold quality
right adrenal gland	UBERON:0001233	93.61	gold quality
ascending aorta	UBERON:0001496	93.61	gold quality
thoracic aorta	UBERON:0001515	93.61	gold quality
left adrenal gland	UBERON:0001234	93.53	gold quality
left adrenal gland cortex	UBERON:0035825	93.38	gold quality
left coronary artery	UBERON:0001626	93.36	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.30	gold quality
skin of leg	UBERON:0001511	93.19	gold quality
skin of abdomen	UBERON:0001416	93.16	gold quality
right adrenal gland cortex	UBERON:0035827	93.16	gold quality
ectocervix	UBERON:0012249	93.07	gold quality
right coronary artery	UBERON:0001625	93.05	gold quality
left uterine tube	UBERON:0001303	92.94	gold quality
lower esophagus mucosa	UBERON:0035834	92.85	gold quality
descending thoracic aorta	UBERON:0002345	92.77	gold quality
aorta	UBERON:0000947	92.67	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.67	gold quality
muscle layer of sigmoid colon	UBERON:0035805	92.64	gold quality
endocervix	UBERON:0000458	92.56	gold quality
popliteal artery	UBERON:0002250	92.49	gold quality
tibial artery	UBERON:0007610	92.49	gold quality
transverse colon	UBERON:0001157	92.45	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.70

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SMAD2, SMAD3, SMAD4

miRNA regulators (miRDB)

72 targeting PSMD9, 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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-2681-5P	99.75	67.64	1655
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-4306	99.72	70.50	3630
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-7152-5P	99.60	69.33	2094

Literature-anchored findings (GeneRIF, showing 40)

• Presence is associated with high nuclear grade, large tumor size, and poor prognosis for glioma patients. (PMID:12778072)
• The researchers found evidence of increased positive identification of p27 following neoadjuvant therapy in colorectal cancer patients, p27 was a good predictor of FR in the pre-radiation biopsy, and p27(+) markers in specimens lived longer at 3 years. (PMID:17360176)
• PSMD9 gene variants contribute rarely to late-onset type 2 diabetes in Italians. (PMID:17516568)
• Polymorphisms of p21 and p27 jointly contribute to an earlier age at diagnosis of pancreatic cancer. (PMID:18694622)
• We report a direct correlation between cyclin D3 and p27 expression in gastrointestinal stromal tumors. (PMID:18701138)
• Bortezomib arrests the proliferation of hepatocellular carcinoma cells HepG2 and JHH6 by differentially affecting p27 level. (PMID:19041685)
• In RCC, p27 is phosphorylated at T157 of the NLS, with increasing tumor grade associated with cytoplasmic p27. (PMID:19118035)
• The expression of p53 and p27 was not related to HPV genotype in cervical carcinomas (PMID:19657726)
• PSMD9 gene in the NIDDM2 locus is linked to type 2 diabetes in Italians. (PMID:19877155)
• Show that the MODY3 mutation and the PSMD9 IVS3 + nt460A/IVS3 + nt437T/G197 SNPs are risk factors for type 2 diabetes in Italian families. (PMID:20069546)
• Cul1 regulates melanoma cell growth and cell cycle progression through degradation of p27 (PMID:20878082)
• Data show that the PSMD9 IVS3 + nt460, IVS3 + nt437, E197G T2D risk SNPs are in linkage with diabetic nephropathy. (PMID:21439668)
• This study is the first to demonstrate the expression of Bridge-1 in human breast carcinomas. Bridge-1 expression is increased by activin A stimulation and itself seems to influence activin A signaling by affecting the expression of Smad2, 3 and 4. (PMID:21448710)
• Analysis of Gem-resistant sub lines also showed that loss of UBE2M and increased p27(Kip1) expression were associated with the acquisition of drug resistance. (PMID:21477582)
• PSMD9 IVS3+nt460A/G, +nt437C/T and exon E197G A/G SNPs are linked to coronary artery disease, stroke/TIA and macrovascular pathology of type 2 diabetes in Italians. (PMID:21496327)
• PSMD9 SNPs IVS3 + nt460 A >G, IVS3 + nt437 C > T and E197G A > G are linked to the hypercholesterolemia phenotype in Italian type 2 diabetes families. (PMID:21554682)
• In summary, the PSMD9 IVS3+nt460, IVS3+nt437, E197G SNPs are linked to diabetic retinopathy and non-diabetic retinopathy in Italians. (PMID:21728808)
• genetic association studies in a population in Italy: SNPs in PSMD9 are strongly linked to diabetic neuropathy in subjects with type 2 diabetes; these associations show significance for an additive model-based inheritance. (PMID:21813292)
• overexpression of Jab1, cytoplasmic p27, and pSer10p27 proteins is correlated with poor outcome in patients with glioma (PMID:21837501)
• Brief Report: PSMD9 SNPs show linkage to carpal tunnel syndrome in Italian type 2 diabetics. (PMID:21862167)
• PSMD9 gene SNPs are linked to elevated blood pressure/hypertension in Italian families with type 2 diabetes. (PMID:21871126)
• the PSMD9 IVS3 + nt460, IVS3 + nt437, E197G SNPs are linked via the recessive model to microvascular pathology of type 2 diabetes (T2D) in Italians (PMID:22015693)
• PSMD9 IVS3+nt460 A>G and +nt437 C>T and exon 5 E197G A>G single nucleotide polymorphisms studied and/or any variants in linkage disequilibrium with them are linked to depression in our type 2 diabetes Italian families. (PMID:22934761)
• The PSMD9 single nucleotide polymorphism(SNP)s IVS3+nt460, IVS3+nt437, and 197G are in linkage with overweight condition and waist circumference in Italians. (PMID:23282078)
• Expression of Hath1, Muc2, cyclin D1 and p27 in the xenograft tumors was also detected. (PMID:23464457)
• Surprisingly, we found that GRP/GRP-R differentially induced expressions of p21 and p27. Silencing GRP/GRP-R decreased p21, but it increased p27 expressions in neuroblastoma cells. (PMID:23618860)
• Our results suggest that tuberin and p27 are aberrantly expressed in malignant breast tissue (PMID:23689538)
• Describe PSMD9 gene SNPs in linkage to generalized anxiety disorder in type 2 diabetic families. (PMID:24648162)
• PSMD9 expression predicts radiotherapy response in breast cancer. (PMID:24673853)
• Staining intensities of cell cycle inhibitors p27 and p57 significantly increased in all parts of preeclamptic placentas compared to control (PMID:24852133)
• The present study provided the first evidences that miR-1470 mediated lapatinib induced p27 upregulation by targeting c-jun. (PMID:25545366)
• The PSMD9 intronic SNPs rs74421874 (IVS3+nt460 G>A) and rs3825172 (IVS3+nt437 C>T) remain significantly associated with insomnia only when taking into account anxiety -and not depression- as covariate. (PMID:26166263)
• recurrence rate of p27 and/or PTEN-negative patients was higher than that of the positive ones,that should be followed up closely after treatment (PMID:26191286)
• p53 immunopositivity was more frequent in SCC (65%) than in VC (23%) (P</=0.001). VC had lower p53 as compared with well-differentiated SCC and SCC without lymph node metastasis. No significant difference was seen in pRb, p16, and p27 expression (PMID:26447892)
• Studies have found significant associations of the treatment response with the 26S proteasome non-ATPase subunit 9 (PSMD9), proteasome alpha type 7 subunit (PSMA7) and PSMD13 genes. (PMID:26624926)
• Loss of p27 associated with risk for endometrial carcinoma arising in the setting of obesity. (PMID:26917264)
• These data suggest that Schistosoma japonicum Sjp40 might inhibit hepatic stellate cell activation by promoting cellular senescence via SKP2/P27 signaling pathway. (PMID:28325896)
• human epidermal growth factor receptor 2 (HER-2) levels, were correlated well with TSP50/p-Samd2/3 and TSP50/p27 expression status. Thus, our studies revealed a novel regulatory mechanism underlying TSP50-induced cell proliferation and provided a new favorable intervention target for the treatment of breast cancer (PMID:28650473)
• Furthermore, inhibition of COPS5 resulted in an elevation of Akt expression and sensitized SOC cells to Akt inhibitor MK2206. Suppression of COPS5 and Akt offers a potential strategy for the treatment of SOC. (PMID:28919423)
• Molecular experiments showed that miR2213p was able to bind with the 3’untranslated region (UTR) of p27 and decreased the expression of p27 in nonsmall cell lung cancer cells. (PMID:31180541)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	psmd9	ENSDARG00000006300
mus_musculus	Psmd9	ENSMUSG00000029440
rattus_norvegicus	Psmd9	ENSRNOG00000077689
drosophila_melanogaster	CG9588	FBGN0038166
caenorhabditis_elegans		WBGENE00016623

Protein

Protein identifiers

26S proteasome non-ATPase regulatory subunit 9 — O00233 (reviewed: O00233)

Alternative names: 26S proteasome regulatory subunit p27

All UniProt accessions (6): O00233, F5GX23, F5H169, F5H5V4, F5H7X1, J3KN29

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a chaperone during the assembly of the 26S proteasome, specifically of the base subcomplex of the PA700/19S regulatory complex (RC). During the base subcomplex assembly is part of an intermediate PSMD9:PSMC6:PSMC3 module, also known as modulator trimer complex; PSMD9 is released during the further base assembly process.

Subunit / interactions. Interacts with PSMC3. Part of a transient complex (modulator) containing PSMD9, PSMC6 and PSMC3 formed during the assembly of the 26S proteasome.

Tissue specificity. Expressed in all tissues tested, highly expressed in liver and kidney.

Similarity. Belongs to the proteasome subunit p27 family.

Isoforms (3)

UniProt ID	Names	Canonical?
O00233-1	p27-L	yes
O00233-2	p27-S
O00233-3	3

RefSeq proteins (2): NP_001248329, NP_002804* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001478	PDZ	Domain
IPR035269	PSMD9	Family
IPR036034	PDZ_sf	Homologous_superfamily
IPR040815	Nas2_N	Domain
IPR041489	PDZ_6	Domain

Pfam: PF17820, PF18265

UniProt features (11 total): sequence variant 4, splice variant 2, chain 1, domain 1, region of interest 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00233-F1	83.53	0.42

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 (1): 129

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9907900	Proteasome assembly

MSigDB gene sets: 208 (showing top): KAAB_FAILED_HEART_ATRIUM_DN, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_INSULIN_SECRETION, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_NEGATIVE_REGULATION_OF_PEPTIDE_SECRETION, GOBP_PROTEASOME_ASSEMBLY, GOBP_HORMONE_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_CELL_CELL_SIGNALING, PUJANA_CHEK2_PCC_NETWORK, GOBP_POSITIVE_REGULATION_OF_INSULIN_SECRETION, GOBP_REGULATION_OF_PROTEIN_SECRETION, MORF_SKP1A

GO Biological Process (5): ubiquitin-dependent protein catabolic process (GO:0006511), positive regulation of insulin secretion (GO:0032024), positive regulation of DNA-templated transcription (GO:0045893), negative regulation of insulin secretion (GO:0046676), proteasome regulatory particle assembly (GO:0070682)

GO Molecular Function (3): transcription coactivator activity (GO:0003713), bHLH transcription factor binding (GO:0043425), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), proteasome regulatory particle (GO:0005838), proteasome regulatory particle, base subcomplex (GO:0008540)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
insulin secretion	2
regulation of insulin secretion	2
cellular anatomical structure	2
protein-containing complex	2
protein ubiquitination	1
modification-dependent protein catabolic process	1
positive regulation of protein secretion	1
positive regulation of peptide hormone secretion	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
negative regulation of protein secretion	1
negative regulation of peptide hormone secretion	1
proteasome assembly	1
transcription coregulator activity	1
positive regulation of DNA-templated transcription	1
DNA-binding transcription factor binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
proteasome accessory complex	1
proteasome regulatory particle	1

Protein interactions and networks

STRING

2576 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PSMD9	PSMC6	P49719	916
PSMD9	SLC13A4	Q9UKG4	864
PSMD9	PSMD12	O00232	789
PSMD9	PSMA3	P25788	781
PSMD9	PSMD6	Q15008	780
PSMD9	PSMD10	O75832	769
PSMD9	PSMC3	P17980	761
PSMD9	PSMD2	Q13200	755
PSMD9	PSMD4	P55036	749
PSMD9	PAAF1	Q9BRP4	743
PSMD9	PSMD13	Q9UNM6	722
PSMD9	ADRM1	Q16186	718
PSMD9	PSMD8	P48556	685
PSMD9	PSMD5	Q16401	679
PSMD9	PSMC4	P43686	595

IntAct

186 interactions, top by confidence:

A	B	Type	Score
PSMC3	PSMD9	psi-mi:“MI:0915”(physical association)	0.940
PSMD9	PSMC6	psi-mi:“MI:0915”(physical association)	0.940
PSMD9	PSMC3	psi-mi:“MI:0915”(physical association)	0.940
PSMC6	PSMD9	psi-mi:“MI:0915”(physical association)	0.940
PSMD9	PSMC3	psi-mi:“MI:0914”(association)	0.940
PSMC3	PSMD9	psi-mi:“MI:0407”(direct interaction)	0.940
PSMC3	PSMD9	psi-mi:“MI:0914”(association)	0.940
PSMD9	TRIM39	psi-mi:“MI:0915”(physical association)	0.670
PSMD9	NCKIPSD	psi-mi:“MI:0915”(physical association)	0.670
TRIM39	PSMD9	psi-mi:“MI:0915”(physical association)	0.670
NCKIPSD	PSMD9	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (273): HNRNPA1 (Reconstituted Complex), CSH1 (Reconstituted Complex), ELSPBP1 (Reconstituted Complex), HNRNPA1 (Protein-peptide), CSH1 (Protein-peptide), ELSPBP1 (Protein-peptide), HNRNPA1 (Affinity Capture-Western), PSMD9 (Two-hybrid), PSMD9 (Two-hybrid), AHCYL1 (Two-hybrid), NCKIPSD (Two-hybrid), BANP (Two-hybrid), TRIM39 (Two-hybrid), CCDC136 (Two-hybrid), TRIM42 (Two-hybrid)

ESM2 similar proteins: A1CDT9, A1DCU5, A3KMV2, I7HUG0, O00233, O17453, O35226, O35987, O61742, O74803, P0CS14, P0CS15, P40087, P54725, P54726, P54727, P54728, P55034, P55035, Q0CJ13, Q0U3Y6, Q10169, Q10256, Q1DNB9, Q1EBV4, Q29RK4, Q2H085, Q2USD7, Q3SZ19, Q40742, Q4I5I4, Q4KMA2, Q4WGS4, Q54JB0, Q54LV1, Q5AY89, Q6BK42, Q6CFI3, Q6CNS3, Q6FQE9

Diamond homologs: O00233, O94393, P40555, Q10920, Q3SZ19, Q8EQU7, Q9CR00, Q9VFS8, Q9WTV5, Q552Y8, O35254, Q9BQQ3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 107 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
Regulation of activated PAK-2p34 by proteasome mediated degradation	7	27.1×	4e-07
Regulation of ornithine decarboxylase (ODC)	7	26.4×	4e-07
Vpu mediated degradation of CD4	7	25.8×	4e-07
Autodegradation of the E3 ubiquitin ligase COP1	7	25.8×	4e-07
Ubiquitin-dependent degradation of Cyclin D	7	25.8×	4e-07
Cross-presentation of soluble exogenous antigens (endosomes)	7	24.7×	4e-07
Vif-mediated degradation of APOBEC3G	7	24.7×	4e-07
AUF1 (hnRNP D0) binds and destabilizes mRNA	7	24.1×	4e-07

GO biological processes:

GO term	Partners	Fold	FDR
proteasome-mediated ubiquitin-dependent protein catabolic process	12	6.4×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1278 predictions. Top by Δscore:

Variant	Effect	Δscore
12:121888947:G:GT	donor_gain	1.0000
12:121888990:A:T	donor_gain	1.0000
12:121888991:AAGC:A	donor_gain	1.0000
12:121888992:AGC:A	donor_gain	1.0000
12:121888993:GC:G	donor_gain	1.0000
12:121888993:GCG:G	donor_gain	1.0000
12:121888994:CG:C	donor_loss	1.0000
12:121888994:CGT:C	donor_loss	1.0000
12:121888995:G:GG	donor_gain	1.0000
12:121888996:T:G	donor_loss	1.0000
12:121888999:GT:G	donor_gain	1.0000
12:121894737:A:AG	acceptor_gain	1.0000
12:121894738:G:GA	acceptor_gain	1.0000
12:121894738:GC:G	acceptor_gain	1.0000
12:121894738:GCA:G	acceptor_gain	1.0000
12:121894738:GCAA:G	acceptor_gain	1.0000
12:121894738:GCAAA:G	acceptor_gain	1.0000
12:121894740:A:AG	acceptor_gain	1.0000
12:121894838:ATAT:A	donor_gain	1.0000
12:121894839:TAT:T	donor_gain	1.0000
12:121894840:AT:A	donor_gain	1.0000
12:121894840:ATG:A	donor_loss	1.0000
12:121894841:TGTG:T	donor_loss	1.0000
12:121894842:G:GG	donor_gain	1.0000
12:121894842:G:T	donor_loss	1.0000
12:121894843:T:G	donor_loss	1.0000
12:121903002:CCA:C	acceptor_loss	1.0000
12:121903003:CA:C	acceptor_loss	1.0000
12:121903004:A:AG	acceptor_gain	1.0000
12:121903004:AG:A	acceptor_gain	1.0000

AlphaMissense

1476 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:121899802:C:A	A137D	0.993
12:121899835:C:A	A148D	0.993
12:121894818:G:C	R73P	0.990
12:121899637:T:C	L82P	0.990
12:121894823:G:C	A75P	0.989
12:121894828:G:C	R76S	0.989
12:121894828:G:T	R76S	0.989
12:121903010:T:C	L153P	0.987
12:121899678:G:C	A96P	0.986
12:121915922:T:A	W208R	0.986
12:121915922:T:C	W208R	0.986
12:121915924:G:C	W208C	0.986
12:121915924:G:T	W208C	0.986
12:121915943:G:C	G215R	0.986
12:121894815:T:A	V72D	0.984
12:121915944:G:A	G215D	0.984
12:121916285:T:C	C216R	0.984
12:121888946:G:C	K30N	0.981
12:121888946:G:T	K30N	0.981
12:121894827:G:C	R76T	0.980
12:121899682:T:C	L97P	0.980
12:121903028:T:A	I159N	0.980
12:121903036:T:C	F162L	0.980
12:121903038:C:A	F162L	0.980
12:121903038:C:G	F162L	0.980
12:121899693:C:G	H101D	0.979
12:121899828:T:C	S146P	0.979
12:121903021:G:C	D157H	0.976
12:121894791:G:C	R64P	0.975
12:121899649:A:C	H86P	0.975

dbSNP variants (sampled 300 via entrez): RS1000063943 (12:121908638 CA>C), RS1000076437 (12:121913789 G>A), RS1000111435 (12:121904263 C>A,T), RS1000123134 (12:121901368 A>C), RS1000132199 (12:121907204 G>C), RS1000216810 (12:121897938 T>C,G), RS1000227806 (12:121903887 T>A), RS1000319931 (12:121895727 A>T), RS1000430211 (12:121889713 G>A), RS1000450189 (12:121905903 A>G), RS1000453949 (12:121910575 G>A), RS1000565433 (12:121905669 A>T), RS1000606388 (12:121897015 T>C), RS1000677312 (12:121912202 G>A), RS1000732438 (12:121895989 A>G)

Disease associations

OMIM: gene MIM:603146 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002184_10	Mean platelet volume	6.000000e-38
GCST002364_32	Urinary metabolites (H-NMR features)	4.000000e-16
GCST012020_191	Serum metabolite levels	8.000000e-11
GCST012021_116	Serum metabolite levels	8.000000e-11
GCST90002392_396	Mean corpuscular volume	9.000000e-15
GCST90002403_462	Red blood cell count	2.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005116	urinary metabolite measurement
EFO:0004305	erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066287 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.05	Kd	90	nM	CHEMBL5653589
7.05	ED50	90	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149132: Binding affinity to human PSMD9 incubated for 45 mins by Kinobead based pull down assay	kd	0.0900	uM

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	2
sodium arsenite	decreases expression	2
triphenyl phosphate	affects expression	1
titanium dioxide	decreases methylation	1
beta-lapachone	increases expression	1
arsenite	increases reaction, affects binding	1
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	1
linalool	increases expression	1
abrine	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Diethylhexyl Phthalate	increases abundance, increases methylation	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	increases O-linked glycosylation, decreases activity	1
Ivermectin	decreases expression	1
Methotrexate	decreases expression	1
Silicon Dioxide	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	increases expression	1
Copper Sulfate	increases expression	1
Particulate Matter	decreases expression, increases abundance	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
CHEMBL5652174	Binding	Binding affinity to human PSMD9 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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