PDCD2

Summary

PDCD2 (programmed cell death 2, HGNC:8762) is a protein-coding gene on chromosome 6q27, encoding uS5 assembly chaperone PDCD2 (Q16342). Chaperone for ribosomal protein uS5; cotranslationally associates with uS5 and accompanies the ribosomal protein to assembly sites in the nucleus; appears to function redundantly to PDCD2L. It is a common-essential gene (DepMap: required in 93.4% of cancer cell lines).

This gene encodes a nuclear protein expressed in a variety of tissues. Expression of this gene has been shown to be repressed by B-cell CLL/lymphoma 6 (BCL6), a transcriptional repressor required for lymph node germinal center development, suggesting that BCL6 regulates apoptosis by its effects on this protein. Alternative splicing results in multiple transcript variants and pseudogenes have been identified on chromosomes 9 and 12.

Source: NCBI Gene 5134 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 54 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 93.4% of screened cell lines (common-essential)
• MANE Select transcript: NM_002598

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8762
Approved symbol	PDCD2
Name	programmed cell death 2
Location	6q27
Locus type	gene with protein product
Status	Approved
Aliases	ZMYND7, RP8
Ensembl gene	ENSG00000071994
Ensembl biotype	protein_coding
OMIM	600866
Entrez	5134

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 7 protein_coding, 6 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000167218, ENST00000392090, ENST00000443345, ENST00000453163, ENST00000537445, ENST00000538195, ENST00000539212, ENST00000541970, ENST00000542896, ENST00000543284, ENST00000544336, ENST00000544755, ENST00000544866, ENST00000545869, ENST00000614056

RefSeq mRNA: 7 — MANE Select: NM_002598 NM_001199461, NM_001199462, NM_001199463, NM_001199464, NM_001363655, NM_002598, NM_144781

CCDS: CCDS47521, CCDS5316, CCDS56460, CCDS56461, CCDS56462, CCDS75557, CCDS87471

Canonical transcript exons

ENST00000541970 — 6 exons

Exon	Start	End
ENSE00000854360	170584299	170584637
ENSE00002263920	170575295	170577717
ENSE00003523653	170578857	170578970
ENSE00003571390	170583057	170583188
ENSE00003637978	170580002	170580105
ENSE00003674892	170583505	170583747

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 96.63.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 86.1524 / max 448.4556, expressed in 1824 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
76830	82.5818	1824
76831	3.5203	1600
76829	0.0503	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	96.63	gold quality
body of pancreas	UBERON:0001150	96.35	gold quality
rectum	UBERON:0001052	95.08	gold quality
cortical plate	UBERON:0005343	94.81	gold quality
pancreas	UBERON:0001264	94.40	gold quality
granulocyte	CL:0000094	94.37	gold quality
calcaneal tendon	UBERON:0003701	94.35	gold quality
body of stomach	UBERON:0001161	94.14	gold quality
lower esophagus mucosa	UBERON:0035834	94.09	gold quality
monocyte	CL:0000576	94.04	gold quality
leukocyte	CL:0000738	93.78	gold quality
mononuclear cell	CL:0000842	93.66	gold quality
esophagus mucosa	UBERON:0002469	93.53	gold quality
right coronary artery	UBERON:0001625	93.52	gold quality
ganglionic eminence	UBERON:0004023	93.49	gold quality
islet of Langerhans	UBERON:0000006	93.42	gold quality
left coronary artery	UBERON:0001626	93.42	gold quality
minor salivary gland	UBERON:0001830	93.34	gold quality
metanephros cortex	UBERON:0010533	93.24	gold quality
descending thoracic aorta	UBERON:0002345	93.17	gold quality
esophagus	UBERON:0001043	93.12	gold quality
left uterine tube	UBERON:0001303	93.09	gold quality
right adrenal gland	UBERON:0001233	93.05	gold quality
mucosa of transverse colon	UBERON:0004991	93.02	gold quality
gastrocnemius	UBERON:0001388	93.01	gold quality
ectocervix	UBERON:0012249	92.96	gold quality
right adrenal gland cortex	UBERON:0035827	92.94	gold quality
left lobe of thyroid gland	UBERON:0001120	92.93	gold quality
thoracic aorta	UBERON:0001515	92.93	gold quality
popliteal artery	UBERON:0002250	92.88	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.64

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BCL6

miRNA regulators (miRDB)

79 targeting PDCD2, 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-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-3924	100.00	72.09	2394
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-153-5P	99.89	73.86	6317
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-4694-3P	99.79	69.53	2640

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 93.4% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 37)

• Basic leucine zipper protein Cnc-C is a substrate and transcriptional regulator of the 26S proteasome. (PMID:21149573)
• Upregulation of the Nrf2 pathway by overexpressing Nrf2 or its DNA-binding dimerization partner, Maf-S, restores the locomotor activity of alpha-synuclein-expressing flies. (PMID:21719443)
• The maintenance of acute stress resistance, motor function, and heart performance in aging flies overexpressing MafS supports a critical role for signal responsiveness of Nrf2 function in promoting youthful phenotypes. (PMID:23521918)
• cooperatively activate developmental genes, in contrast to their conserved antagonizing effect to xenobiotic response transcription (PMID:24406335)
• dKeap1 and CncC have a xenobiotic-specific gene activation response due to their combinatorial chromatin-binding specificities and transcriptional activities (PMID:25063457)
• Selective expression of the Nrf2 homologous gene cncC in the dopaminergic neurons effectively protected against the neurodegenerative phenotype of the A53T alpha-synuclein flies, compared to the flies that expressed cncC in all neurons (PMID:26008822)
• CncCDeltaN induced a number of genes related to innate immunity that might have an effect on the regulation of cellular lipid storage (PMID:26049108)
• Our findings demonstrated that lovastatin restored LRRK2-G2019S neurite degeneration by augmenting Akt/NRF2 pathway and inhibiting downstream GSK3b activity, which decreased phospho-tau levels. We suggested that lovastatin is a potential disease-modifying agent for LRRK2-G2019S parkinsonism. (PMID:26931464)
• Knockdown of the Drosophila Nrf1 and Nrf2 ortholog cap ’n’ collar isoform-C, but not Hsf1, blocks the protective effect of ASC-JM17 on mutant AR-induced eye degeneration in flies. Our observations indicate that activation of the Nrf1/Nrf2 pathway is a viable option for pharmacological intervention in SBMA and potentially other polyglutamine diseases. (PMID:26962150)
• Consistent with the independent modes of CncC regulation by Keap1 and Fs(1)h, combinations of drugs that can specifically target these pathways cause a strong synergistic and specific activation of protective CncC- dependent gene expression and boosts oxidative stress resistance. (PMID:27233051)
• Data suggest that blocking the specific interaction of Nrf2/cncC (cap-n-collar isoform C) with Keap1 may provide an exciting new avenue for the discovery of disease-modifying treatments for Alzheimer’s disease (AD) and potentially other neurodegenerative conditions. (PMID:28253260)
• continual knockdown of Keep1 (the cytosolic inhibitor of Cnc-C) in adults resulted in older flies with greater stress resistance than their age-matched controls, but who still exhibited an age-associated loss of adaptive homeostasis (PMID:28373600)
• Cnc is required for tissue regeneration. Cnc regulates reactive oxygen species levels in the regenerating wing imaginal disc, and affects JNK signaling. (PMID:28512185)
• Together with the facts that Maf-S regulates ROS levels and genetically interacts with Keap1/Nrf2 in GSC maintenance, our study suggests that Maf-S plays an important role in the Drosophila testis GSC maintenance by participating in the regulation of redox homeost (PMID:29245136)
• increased expression of nuclear factor erythroid 2-related factor (Nrf2) in Drosophila activated cytoprotective modules and enhanced stress tolerance. (PMID:30537423)
• Study shows that Drosophila CncC links cell cycle control with proteostatic responses in intestinal stem cells via the accumulation of dacapo, a p21 cell cycle inhibitor homologue, as well as the transcriptional activation of genes encoding proteases and proteasome subunits. (PMID:30837466)
• Mutations in genes cnc or dKeap1 modulate stress resistance and metabolic processes in Drosophila melanogaster. (PMID:32579905)
• Preserving transcriptional stress responses as an anti-aging strategy. (PMID:33474790)
• Nrf2 activation induces mitophagy and reverses Parkin/Pink1 knock down-mediated neuronal and muscle degeneration phenotypes. (PMID:34218254)
• Activation of Nrf2 in Astrocytes Suppressed PD-Like Phenotypes via Antioxidant and Autophagy Pathways in Rat and Drosophila Models. (PMID:34440619)
• Xrp1 and Irbp18 trigger a feed-forward loop of proteotoxic stress to induce the loser status. (PMID:34914692)
• Determination of Complex Formation between Drosophila Nrf2 and GATA4 Factors at Selective Chromatin Loci Demonstrates Transcription Coactivation. (PMID:36980279)
• Sustained Nrf2 Overexpression-Induced Metabolic Deregulation Can Be Attenuated by Modulating Insulin/Insulin-like Growth Factor Signaling. (PMID:37998385)
• Interplay between autophagy and CncC regulates dendrite pruning in Drosophila. (PMID:38408233)
• To study the role of PDCD2_C domain in apoptosis, the cDNAs of two isoforms of PDCD2 and MGC13096 were cloned. PDCD2 (NM_002598) was over expressed when endothelial cells treated with leukotriene D4 or natural killer cells were activated by IL-2. (PMID:16311922)
• repression of PDCD2 by BCL6 is likely important in the pathogenesis of certain human lymphomas (PMID:17468402)
• parkin interacts with programmed cell death-2 isoform 1 (PDCD2-1) (PMID:19146857)
• Transfection of a construct expressing PDCD2 induces apoptosis in human cell lines through activation of the caspase cascade. (PMID:20605493)
• PDCD2 has a novel regulatory role in human hematopoiesis and is essential for erythroid development. (PMID:22922207)
• PDCD2 RNA expression in acute leukemia patients correlates with disease status and is a significant predictor of clinical relapse. (PMID:23760497)
• Expression of human PDCD2 fully rescues the Drosophila Zfrp8 phenotype, underlining the functional conservation of Zfrp8/PDCD2. (PMID:24381196)
• Low PDCD2 expression is associated with gastric cancer. (PMID:25111461)
• Loss of PDCD2 expression could contribute to gastric cancer development and progression. (PMID:25334010)
• PDCD2 and NCoR1 may act as tumor suppressors in Gastrointestinal stromal tumors cells through the Smad signaling pathway. (PMID:26589942)
• PDCD2 may play an important role in tumor suppression in osteosarcoma. These mechanisms might be related to immune response induced by CD4(+) and CD8(+) T cells. (PMID:26617804)
• the present study elucidated for the first time, to the best of our knowledge, that PDCD2 sensitizes sorafenibresistant HepG2 cells to sorafenib by the downregulation of EMT. PDCD2 may serve as a potential therapeutic target in the treatment of sorafenibresistant liver cancer. (PMID:30664177)
• PDCD2 functions as an evolutionarily conserved chaperone dedicated for the 40S ribosomal protein uS5 (RPS2). (PMID:33245768)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pdcd2	ENSDARG00000007892
mus_musculus	Pdcd2	ENSMUSG00000014771
rattus_norvegicus	Pdcd2	ENSRNOG00000001490
drosophila_melanogaster	Zfrp8	FBGN0021875
caenorhabditis_elegans		WBGENE00011116

Paralogs (2): ZMYND12 (ENSG00000066185), PDCD2L (ENSG00000126249)

Protein

Protein identifiers

uS5 assembly chaperone PDCD2 — Q16342 (reviewed: Q16342)

Alternative names: Programmed cell death protein 2, Zinc finger MYND domain-containing protein 7, Zinc finger protein Rp-8

All UniProt accessions (8): Q16342, A0A087WYJ3, F5GWT2, F5H4V9, H0YFM2, H0YFS8, H0YFZ5, J3QK82

UniProt curated annotations — full annotation on UniProt →

Function. Chaperone for ribosomal protein uS5; cotranslationally associates with uS5 and accompanies the ribosomal protein to assembly sites in the nucleus; appears to function redundantly to PDCD2L.

Subunit / interactions. Interacts with small ribosomal subunit protein RPS2/uS5; the interaction is direct, occurs cotranslationally, and serves to chaperone uS5 to assembly sites in the nucleus.

Subcellular location. Nucleus. Nucleolus. Cytoplasm. Cytosol.

Tissue specificity. Ubiquitous.

Post-translational modifications. Ubiquitinated by PRKN, promoting proteasomal degradation.

Similarity. Belongs to the TSR4 family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q16342-1	1	yes
Q16342-2	2
Q16342-3	3
Q16342-4	4
Q16342-5	5

RefSeq proteins (7): NP_001186390, NP_001186391, NP_001186392, NP_001186393, NP_001350584, NP_002589, NP_659005 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002893	Znf_MYND	Domain
IPR007320	PDCD2_C	Domain

Pfam: PF01753, PF04194

UniProt features (20 total): binding site 8, splice variant 6, sequence conflict 2, region of interest 2, chain 1, zinc finger region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16342-F1	85.33	0.65

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 (8): 168; 172; 135; 138; 146; 149; 155; 159

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 149 (showing top): GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, GOBP_RIBOSOME_BIOGENESIS, KYNG_DNA_DAMAGE_BY_4NQO, RIZKI_TUMOR_INVASIVENESS_3D_DN, GOBP_RIBOSOMAL_SMALL_SUBUNIT_BIOGENESIS, LEE_METASTASIS_AND_ALTERNATIVE_SPLICING_DN, GOTZMANN_EPITHELIAL_TO_MESENCHYMAL_TRANSITION_DN, LIAO_METASTASIS, GOBP_REGULATION_OF_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, MODULE_113, CAIRO_HEPATOBLASTOMA_UP, BASAKI_YBX1_TARGETS_UP, ZAMORA_NOS2_TARGETS_UP, chr6q27, GERHOLD_ADIPOGENESIS_DN

GO Biological Process (6): apoptotic process (GO:0006915), ribosomal small subunit biogenesis (GO:0042274), regulation of hematopoietic progenitor cell differentiation (GO:1901532), programmed cell death (GO:0012501), positive regulation of apoptotic process (GO:0043065), positive regulation of hematopoietic stem cell proliferation (GO:1902035)

GO Molecular Function (6): DNA binding (GO:0003677), zinc ion binding (GO:0008270), enzyme binding (GO:0019899), protein carrier activity (GO:0140597), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): nucleus (GO:0005634), nucleolus (GO:0005730), cytosol (GO:0005829), extracellular exosome (GO:0070062), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
ribonucleoprotein complex biogenesis	1
ribosome biogenesis	1
hematopoietic progenitor cell differentiation	1
regulation of cell differentiation	1
signal transduction	1
cell death	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
hematopoietic stem cell proliferation	1
regulation of hematopoietic stem cell proliferation	1
positive regulation of stem cell proliferation	1
nucleic acid binding	1
transition metal ion binding	1
protein binding	1
molecular carrier activity	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular membraneless organelle	1
cytoplasm	1
extracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1132 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PDCD2	PSMB1	P20618	665
PDCD2	BCL6	P41182	639
PDCD2	FAM120B	Q96EK7	594
PDCD2	TBP	P20226	534
PDCD2	MYBL1	P10243	510
PDCD2	GPR183	P32249	497
PDCD2	BCL7A	Q4VC05	497
PDCD2	ZNF277	Q9NRM2	443
PDCD2	IL21	Q9HBE4	438
PDCD2	MS4A1	P08984	437
PDCD2	PDE10A	Q9Y233	426
PDCD2	IFITM1	P13164	423
PDCD2	KCNG3	Q8TAE7	419
PDCD2	PNO1	Q9NRX1	415
PDCD2	LTV1	Q96GA3	411

IntAct

57 interactions, top by confidence:

A	B	Type	Score
PRMT3	RPS2	psi-mi:“MI:0914”(association)	0.810
USP43	YWHAB	psi-mi:“MI:0914”(association)	0.640
SLC17A5	LGALS8	psi-mi:“MI:0914”(association)	0.640
PDCD2	RPS2	psi-mi:“MI:0915”(physical association)	0.620
PDCD2	TBC1D21	psi-mi:“MI:0915”(physical association)	0.560
CYC1	PDCD2	psi-mi:“MI:0915”(physical association)	0.560
YWHAG	PDCD2	psi-mi:“MI:0915”(physical association)	0.560
SETDB1	PDCD2	psi-mi:“MI:0915”(physical association)	0.560
KAT5	PDCD2	psi-mi:“MI:0915”(physical association)	0.560
LMO3	PDCD2	psi-mi:“MI:0915”(physical association)	0.560
RPS2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
MGRN1	ATRN	psi-mi:“MI:0914”(association)	0.530
IL1R2	EXOC5	psi-mi:“MI:0914”(association)	0.530
ABHD15	HSPA8	psi-mi:“MI:0914”(association)	0.530
PDCD2	PRKN	psi-mi:“MI:0915”(physical association)	0.510

BioGRID (58): PDCD2 (Affinity Capture-MS), PDCD2 (Affinity Capture-MS), PDCD2 (Two-hybrid), PDCD2 (Affinity Capture-MS), PDCD2 (Affinity Capture-MS), PDCD2 (Affinity Capture-MS), PDCD2 (Affinity Capture-MS), PDCD2 (Affinity Capture-MS), TBC1D21 (Two-hybrid), PDCD2 (Two-hybrid), HCFC1 (Reconstituted Complex), HCFC1 (Affinity Capture-Western), NCOR1 (Affinity Capture-Western), CD59 (Affinity Capture-MS), RHOA (Affinity Capture-MS)

ESM2 similar proteins: A0A1L1SUL6, F1LQY6, O35465, O43379, O75293, O88910, O88954, P0C0T1, P21964, P22339, P41214, P50747, Q13368, Q13572, Q14318, Q16342, Q1HAQ0, Q28955, Q2T9Z1, Q3B7U9, Q3TFD2, Q3TMX7, Q496Y0, Q4AC99, Q5BIM1, Q5E9A5, Q5R812, Q5RA63, Q5SZD4, Q64311, Q6DC64, Q6P5G6, Q6PFY8, Q80YV4, Q8BNV1, Q8BYN3, Q8NFZ0, Q8R1C6, Q8R1T1, Q8TCU6

Diamond homologs: P25040, P46718, P47816, P87156, Q09787, Q16342, Q2YDC9, Q67XW5, Q9BRP1, Q9SB51, Q5ZID2, Q8C5N5, Q9FK27, Q9FYF9

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 50 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
G2/M Checkpoints	5	18.7×	3e-03

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	45
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

794 predictions. Top by Δscore:

Variant	Effect	Δscore
6:170578583:A:C	donor_gain	1.0000
6:170578851:TCATA:T	donor_loss	1.0000
6:170578852:CATA:C	donor_loss	1.0000
6:170578853:ATAC:A	donor_loss	1.0000
6:170578854:TACCT:T	donor_loss	1.0000
6:170578856:C:T	donor_loss	1.0000
6:170579996:CTTTA:C	donor_loss	1.0000
6:170579997:TTTA:T	donor_loss	1.0000
6:170579998:TTAC:T	donor_loss	1.0000
6:170579999:TA:T	donor_loss	1.0000
6:170580001:C:A	donor_loss	1.0000
6:170580055:C:A	donor_gain	1.0000
6:170580102:TCACC:T	acceptor_loss	1.0000
6:170580103:CAC:C	acceptor_gain	1.0000
6:170580103:CACCT:C	acceptor_loss	1.0000
6:170580104:ACCT:A	acceptor_loss	1.0000
6:170580106:C:CC	acceptor_gain	1.0000
6:170580106:CT:C	acceptor_loss	1.0000
6:170583051:GCTTA:G	donor_loss	1.0000
6:170583052:CTTA:C	donor_loss	1.0000
6:170583053:TTA:T	donor_loss	1.0000
6:170583054:TACCC:T	donor_loss	1.0000
6:170583055:A:AC	donor_gain	1.0000
6:170583055:AC:A	donor_gain	1.0000
6:170583055:ACCCA:A	donor_loss	1.0000
6:170583056:C:CC	donor_gain	1.0000
6:170583056:CC:C	donor_gain	1.0000
6:170583064:C:CA	donor_gain	1.0000
6:170583086:T:TA	donor_gain	1.0000
6:170583185:TGAT:T	acceptor_gain	1.0000

AlphaMissense

2260 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:170583741:C:A	R97M	0.994
6:170584357:G:C	F75L	0.992
6:170584357:G:T	F75L	0.992
6:170584359:A:G	F75L	0.992
6:170577660:A:G	W312R	0.991
6:170577660:A:T	W312R	0.991
6:170584473:A:G	W37R	0.991
6:170584473:A:T	W37R	0.991
6:170583628:A:G	C135R	0.989
6:170584492:C:A	K30N	0.989
6:170584492:C:G	K30N	0.989
6:170584543:G:C	F13L	0.988
6:170584543:G:T	F13L	0.988
6:170584545:A:G	F13L	0.988
6:170577704:A:G	L297P	0.987
6:170583741:C:G	R97T	0.986
6:170584487:C:T	G32D	0.986
6:170583740:C:A	R97S	0.984
6:170583740:C:G	R97S	0.984
6:170578966:A:G	L256P	0.982
6:170584488:C:G	G32R	0.982
6:170577716:A:T	V293D	0.981
6:170583619:A:G	C138R	0.981
6:170583626:G:C	C135W	0.981
6:170584495:G:C	S29R	0.981
6:170584495:G:T	S29R	0.981
6:170584497:T:G	S29R	0.981
6:170580032:A:C	F244L	0.980
6:170580032:A:T	F244L	0.980
6:170580034:A:G	F244L	0.980

dbSNP variants (sampled 300 via entrez): RS1000250781 (6:170576709 G>T), RS1000348045 (6:170585133 T>G), RS1000518253 (6:170582540 C>T), RS1000566871 (6:170578674 A>G), RS1000576659 (6:170578391 T>C), RS1001077001 (6:170578742 T>G), RS1001358123 (6:170575799 A>T), RS1001626835 (6:170584481 C>A,G), RS1002229704 (6:170583253 G>C,T), RS1002352305 (6:170578064 A>G), RS1003348473 (6:170585434 T>C), RS1003408583 (6:170576264 A>G,T), RS1003762530 (6:170576601 T>A), RS1003870430 (6:170580373 C>T), RS1003949935 (6:170585754 G>C)

Disease associations

OMIM: gene MIM:600866 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST004250_33	Alanine aminotransferase (ALT) levels after remission induction therapy in actute lymphoblastic leukemia (ALL)	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007965	response to combination chemotherapy

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066022 (PROTEIN-PROTEIN INTERACTION)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
Arsenic Trioxide	decreases reaction, increases expression, affects binding	2
Sodium Selenite	increases expression	2
TAK-243	increases sumoylation	1
beauvericin	decreases expression	1
decabromobiphenyl ether	affects expression	1
trichostatin A	affects expression	1
beta-lapachone	decreases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
beta-methylcholine	affects expression	1
U 0126	affects expression, affects reaction	1
Resveratrol	increases expression	1
Sunitinib	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Allergens	increases expression	1
Arsenates	affects cotreatment, increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Atrazine	affects cotreatment, increases expression	1
Cycloheximide	increases expression, decreases reaction	1
Hydrogen Peroxide	decreases expression	1
Lead	affects expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Menthol	decreases expression	1
Ozone	affects expression, increases abundance	1
Tetrachlorodibenzodioxin	decreases reaction, increases expression	1
Tretinoin	decreases expression	1
1-Methyl-4-phenylpyridinium	affects expression, affects reaction	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
CHEMBL5535494	Binding	Protac activity at CRBN/PDCD2 in human NCI-H226 cells at 0.01 to 10 uM incubated for 24 hrs by Western blot analysis	Design, Synthesis, and Bioevaluation of Transcriptional Enhanced Assocciated Domain (TEAD) PROTAC Degraders. — ACS Med Chem Lett

Clinical trials (associated diseases)

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