PDCD5

Summary

PDCD5 (programmed cell death 5, HGNC:8764) is a protein-coding gene on chromosome 19q13.11, encoding Programmed cell death protein 5 (O14737). In response to DNA damage, associates with TP53/p53 to prevent MDM2-mediated degradation of TP53 and promote TP53-mediated signaling. It is a selective cancer dependency (DepMap: 45.0% of cell lines).

This gene encodes a protein that is upregulated during apoptosis where it translocates rapidly from the cytoplasm to the nucleus. The encoded protein may be an important regulator of K(lysine) acetyltransferase 5 (a protein involved in transcription, DNA damage response and cell cycle control) by inhibiting its proteasome-dependent degradation. Pseudogenes have been identified on chromosomes 5 and 12

Source: NCBI Gene 9141 — RefSeq curated summary.

At a glance

• GWAS associations: 21
• Clinical variants (ClinVar): 26 total
• GTEx eGene: eQTL in 45 tissues, sQTL in 27 (q < 0.05)
• Cancer dependency (DepMap): dependent in 45.0% of screened cell lines
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.84 (unconstrained)
• MANE Select transcript: NM_004708
• Interaction hub: 2,074 STRING partners (top 7% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8764
Approved symbol	PDCD5
Name	programmed cell death 5
Location	19q13.11
Locus type	gene with protein product
Status	Approved
Aliases	TFAR19, MGC9294
Ensembl gene	ENSG00000105185
Ensembl biotype	protein_coding
OMIM	604583
Entrez	9141

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 15 protein_coding, 13 nonsense_mediated_decay, 2 retained_intron

MANE Select: ENST00000590247

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 3, TSL 3: 3

ENST00000590247, ENST00000221784, ENST00000379316, ENST00000419343, ENST00000586035, ENST00000586316, ENST00000588622, ENST00000592786, ENST00000884500, ENST00000912659, ENST00000912660, ENST00000912661, ENST00001004809, ENST00001004810, ENST00001004811, ENST00001009102, ENST00001060070, ENST00001060071, ENST00001060072, ENST00001060073, ENST00001060077, ENST00001060078, ENST00001060082, ENST00001060086, ENST00001094653, ENST00001094654, ENST00001094655, ENST00001114980, ENST00001123445, ENST00001136705

RefSeq mRNA: 1 — MANE Select: NM_004708 NM_004708

CCDS: CCDS12423

Canonical transcript exons

ENST00000590247 — 6 exons

Exon	Start	End
ENSE00002747495	32581190	32581327
ENSE00003466331	32587253	32587453
ENSE00003480931	32586858	32586929
ENSE00003541929	32585816	32585907
ENSE00003703183	32584950	32585011
ENSE00003703838	32582195	32582232

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 99.07.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 197.7003 / max 1176.2429, expressed in 1827 samples.

Highest expression (Bgee): testis, body of pancreas, adenohypophysis, atrium auricular region, lower esophagus.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PDCD5 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 45 tissues and its splicing (sQTL) in 27 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 72 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Muscle Skeletal	eqtl	1.7e-65	+0.53	19:32581163:G:A
Whole Blood	eqtl	8.7e-48	+0.39	19:32581163:G:A
Cells Cultured fibroblasts	eqtl	2.9e-43	+0.20	19:32583708:A:C
Heart Left Ventricle	eqtl	2.6e-37	+0.36	19:32583708:A:C
Esophagus Muscularis	eqtl	6.2e-37	+0.40	19:32583708:A:C
Brain Frontal Cortex BA9	eqtl	5.0e-36	+0.59	19:32583708:A:C
Artery Tibial	eqtl	1.2e-35	+0.30	19:32583708:A:C
Cells Cultured fibroblasts	sqtl	2.2e-35	-1.04	19:32599365:T:C
Brain Cortex	eqtl	3.8e-35	+0.73	19:32583708:A:C
Colon Transverse	eqtl	2.5e-34	+0.41	19:32581163:G:A
Brain Caudate basal ganglia	eqtl	2.0e-32	+0.45	19:32583708:A:C
Brain Nucleus accumbens basal ganglia	eqtl	1.9e-30	+0.45	19:32583708:A:C
Esophagus Mucosa	eqtl	3.9e-29	+0.30	19:32583708:A:C
Thyroid	eqtl	3.4e-26	+0.28	19:32581179:A:G
Adipose Visceral Omentum	eqtl	8.5e-26	+0.31	19:32583708:A:C
Esophagus Mucosa	sqtl	2.8e-25	-1.93	19:32599365:T:C
Brain Hypothalamus	eqtl	2.0e-24	+0.46	19:32583708:A:C
Heart Atrial Appendage	eqtl	2.9e-24	+0.33	19:32583708:A:C
Brain Putamen basal ganglia	eqtl	5.8e-24	+0.47	19:32583708:A:C
Esophagus Gastroesophageal Junction	eqtl	9.9e-24	+0.39	19:32583708:A:C

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
175056	183.8310	1827
175057	11.9696	1635
175058	1.8997	779

Top tissues by expression

showing 100 of 286 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	99.07	gold quality
left testis	UBERON:0004533	99.06	gold quality
body of pancreas	UBERON:0001150	98.57	gold quality
adenohypophysis	UBERON:0002196	98.55	gold quality
right atrium auricular region	UBERON:0006631	98.44	gold quality
lower esophagus	UBERON:0013473	98.44	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.44	gold quality
left coronary artery	UBERON:0001626	98.35	gold quality
cortical plate	UBERON:0005343	98.34	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.32	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.32	gold quality
adrenal tissue	UBERON:0018303	98.30	gold quality
mucosa of stomach	UBERON:0001199	98.28	gold quality
apex of heart	UBERON:0002098	98.21	gold quality
anterior cingulate cortex	UBERON:0009835	98.15	gold quality
tibial artery	UBERON:0007610	98.12	gold quality
popliteal artery	UBERON:0002250	98.11	gold quality
left adrenal gland cortex	UBERON:0035825	98.10	gold quality
right coronary artery	UBERON:0001625	98.07	gold quality
descending thoracic aorta	UBERON:0002345	98.05	gold quality
left adrenal gland	UBERON:0001234	98.03	gold quality
tibial nerve	UBERON:0001323	98.03	gold quality
ascending aorta	UBERON:0001496	98.02	gold quality
thoracic aorta	UBERON:0001515	98.02	gold quality
right ovary	UBERON:0002118	98.01	gold quality
cingulate cortex	UBERON:0003027	98.00	gold quality
aorta	UBERON:0000947	97.99	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	97.98	gold quality
left ovary	UBERON:0002119	97.94	gold quality
gastrocnemius	UBERON:0001388	97.93	gold quality
left uterine tube	UBERON:0001303	97.91	gold quality
right frontal lobe	UBERON:0002810	97.90	gold quality
omental fat pad	UBERON:0010414	97.90	gold quality
peritoneum	UBERON:0002358	97.89	gold quality
body of uterus	UBERON:0009853	97.87	gold quality
right adrenal gland	UBERON:0001233	97.86	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.84	gold quality
lower esophagus mucosa	UBERON:0035834	97.82	gold quality
cerebellar hemisphere	UBERON:0002245	97.80	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.79	gold quality
ectocervix	UBERON:0012249	97.78	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.78	gold quality
cerebellar cortex	UBERON:0002129	97.76	gold quality
colonic epithelium	UBERON:0000397	97.75	gold quality
ganglionic eminence	UBERON:0004023	97.74	gold quality
minor salivary gland	UBERON:0001830	97.62	gold quality
right adrenal gland cortex	UBERON:0035827	97.62	gold quality
esophagus	UBERON:0001043	97.59	gold quality
muscle of leg	UBERON:0001383	97.56	gold quality
testis	UBERON:0000473	97.55	gold quality
coronary artery	UBERON:0001621	97.52	gold quality
metanephros cortex	UBERON:0010533	97.48	gold quality
endocervix	UBERON:0000458	97.44	gold quality
adipose tissue of abdominal region	UBERON:0007808	97.40	gold quality
body of stomach	UBERON:0001161	97.37	gold quality
calcaneal tendon	UBERON:0003701	97.37	gold quality
transverse colon	UBERON:0001157	97.32	gold quality
adrenal cortex	UBERON:0001235	97.30	gold quality
ventricular zone	UBERON:0003053	97.25	gold quality
left lobe of thyroid gland	UBERON:0001120	97.20	gold quality
nucleus accumbens	UBERON:0001882	97.14	gold quality
heart left ventricle	UBERON:0002084	97.09	gold quality
upper lobe of left lung	UBERON:0008952	97.08	gold quality
skin of abdomen	UBERON:0001416	97.06	gold quality
amygdala	UBERON:0001876	97.05	gold quality
adrenal gland	UBERON:0002369	97.00	gold quality
esophagus mucosa	UBERON:0002469	96.98	gold quality
right lobe of thyroid gland	UBERON:0001119	96.95	gold quality
tendon	UBERON:0000043	96.94	gold quality
right lung	UBERON:0002167	96.94	gold quality
pituitary gland	UBERON:0000007	96.93	gold quality
cardiac ventricle	UBERON:0002082	96.87	gold quality
rectum	UBERON:0001052	96.86	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	96.85	gold quality
right uterine tube	UBERON:0001302	96.83	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.82	gold quality
caudate nucleus	UBERON:0001873	96.73	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.73	gold quality
right lobe of liver	UBERON:0001114	96.71	gold quality
skin of leg	UBERON:0001511	96.66	gold quality
mucosa of transverse colon	UBERON:0004991	96.59	gold quality
prefrontal cortex	UBERON:0000451	96.51	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.47	gold quality
saliva-secreting gland	UBERON:0001044	96.32	gold quality
cerebellum	UBERON:0002037	96.29	gold quality
tendon of biceps brachii	UBERON:0008188	96.22	gold quality
heart	UBERON:0000948	96.17	gold quality
putamen	UBERON:0001874	96.15	gold quality
thyroid gland	UBERON:0002046	96.14	gold quality
islet of Langerhans	UBERON:0000006	96.11	gold quality
spinal cord	UBERON:0002240	96.06	gold quality
mouth mucosa	UBERON:0003729	96.06	gold quality
pancreas	UBERON:0001264	95.88	gold quality
upper lobe of lung	UBERON:0008948	95.88	gold quality
stomach	UBERON:0000945	95.85	gold quality
subcutaneous adipose tissue	UBERON:0002190	95.47	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.36	gold quality
monocyte	CL:0000576	95.34	gold quality
oocyte	CL:0000023	95.10	gold quality
vagina	UBERON:0000996	95.10	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-8381	yes	3938.53
E-GEOD-134144	yes	27.62
E-ANND-3	yes	13.26
E-CURD-112	yes	10.09
E-MTAB-9067	yes	9.98

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Skeletal muscle	tissue	210.2	not detected
Tongue	tissue	123.3
Putamen	tissue	117.7
Cerebral cortex	tissue	106.2	low
Motor cortex	tissue	106.2
Heart muscle	tissue	105.9	not detected
Pituitary gland	tissue	105.5
Testis	tissue	101.9	high
Pancreas	tissue	96.5	low
Pons	tissue	96.4
Corpus callosum	tissue	91.8
Vagina	tissue	91.3	not detected
Insular cortex	tissue	88.9
Retrosplenial and cingulate cortex	tissue	87.8
Hippocampal formation	tissue	86.2
Entorhinal cortex	tissue	86.2
Amygdala	tissue	86.1
Periaqueductal gray	tissue	86.0
Liver	tissue	83.7	not detected
Temporal cortex	tissue	83.7
Adrenal gland	tissue	83.4	medium
Occipital cortex	tissue	83.0
Prefrontal cortex	tissue	82.3
Hypothalamus	tissue	82.0
Somatosensory cortex	tissue	81.9
Medulla oblongata	tissue	81.7
Thalamus	tissue	81.7
Midbrain	tissue	80.4
Retrosplenial cortex	tissue	79.3
Basal ganglia	tissue	79.1	not detected
Substantia nigra	tissue	77.5
Septum	tissue	76.3
Superior colliculi	tissue	75.6
Ventral forebrain	tissue	75.4
Adipose tissue	tissue	71.8	low
Appendix	tissue	69.6	medium
Ovary	tissue	69.4	medium
Spinal cord	tissue	69.3
Colon	tissue	66.9	medium
Urinary bladder	tissue	65.8	medium
Caudate putamen	tissue	64.0
Duodenum	tissue	61.8	medium
Frontal cortex	tissue	61.6
Smooth muscle	tissue	61.4	not detected
Placenta	tissue	57.4	high
Stomach 1	tissue	57.3	low
Esophagus	tissue	56.6	low
Salivary gland	tissue	55.9	low
Tonsil	tissue	55.6	medium
Small intestine	tissue	54.8	medium
Lymph node	tissue	54.7	low
Kidney	tissue	53.9	low
Rectum	tissue	52.3	medium
Cerebellum	tissue	50.8	not detected
Breast	tissue	50.7	medium
Parathyroid gland	tissue	49.3	medium
Postcentral gyrus	tissue	48.2
Locus coeruleus	tissue	48.1
Epididymis	tissue	48.0	not detected
Skin 1	tissue	46.5	high

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Blood vessel (118.4), White matter (91.8), Dorsal hippocampus (79.4), Subiculum (79.0), Ventral hippocampus (73.6).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets:

Target	Regulation
FOXP3	Activation

Upstream regulators (CollecTRI, top): CTNNB1, DNMT1, KLF9, NFKB, NR0B2, RELA

miRNA regulators (miRDB)

Targeting PDCD5 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 31 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-4677-3P	99.49	67.91	1246
HSA-MIR-148A-5P	99.30	68.27	1141
HSA-MIR-3973	99.20	69.19	1990

Functional genomics

gnomAD constraint: pLI 2.59e-07, LOEUF 1.84, missense Z -1.17 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000590247 — one region, missense o/e 1.03. DepMap (CRISPR cell-line fitness): dependent in 45.0% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): IST-MES2 (-1.397), EPLC-272H (-1.378), LN-443 (-1.302), DU 145 (-1.294), G-402 (-1.25), H4 (-1.222), NCI-H460 (-1.201), PE/CA-PJ49 (-1.199), 647-V (-1.186), SNU-840 (-1.185), SK-N-AS (-1.172), TEN (-1.164), LN-229 (-1.159), SNU-387 (-1.139), L-363 (-1.136).

Literature-anchored findings (GeneRIF, showing 40)

• Results imply that the PDCD5 gene may be a target gene under the control of some important apoptosis-related transcriptional factors during the cell apoptosis. (PMID:15033527)
• The effects of the secondary structure of PDCD5 on its tertiary structure and function are reported. (PMID:16083422)
• Data show that the number of apoptotic cells in renal tubuli with lupus nephritis correlated negatively with the intensity of PDCD5 expression. (PMID:16083554)
• -27G/-11A SNP is associated with reduced PDCD5 promoter activity and increased susceptibility to chronic myelogenous leukemia. (PMID:16361542)
• Could play an important role in regulation of apoptotic processes in gastric cancer cells and gastric tumors. (PMID:16547588)
• PDCD5 may be involved in the pathogenesis of rheumatoid arthritis. (PMID:17468978)
• PDCD5 expression in bone marrow nucleated cells in untreated acute myeloid leukemia patients is lower than in normal controls. (PMID:17605845)
• exogenous PDCD5 expression enhances the chemosensitivity of K562 leukemia cells to either low or high doses of idarubicin in vitro, resulting in increased apoptosis. (PMID:18401719)
• Reduced expression of PDCD5 is associated with high-grade astrocytic gliomas (PMID:18695908)
• Overexpression of PDCD5 could enhance apoptosis of rheumatoid arthritis fibroblast-like synoviocytes induced by triptolide. (PMID:19088824)
• PDCD5 contributes to maintaining a basal pool of Tip60 and its HAT activity (PMID:19308289)
• Studies of structure-function relationship of PDCD5 by multidimensional NMR methods and flow cytometer and fluorescence microscopey. (PMID:19358820)
• these results suggest a functional link between the CK2 phosphorylation and the apoptotic potential of PDCD5. (PMID:19616514)
• PDCDS was highly expressed in some ragged red fibers in patients with limb-girdle type mitochondrial myopathy and chronic progressive external ophthalmoplegia. (PMID:19957502)
• protein overexpression enhance apoptosis in triptolide-induced synoviocytes of rheumatoid arthritis patients (PMID:20047520)
• By downregulating apoptosis, low PDCD5 expression may play an important role in the occurrence and development of PAROSTATIC NEOPLASM. (PMID:20120772)
• Abnormal expression of pdcd5 may be involved in the pathogenesis of multiple myeloma. (PMID:20561417)
• Downregulated expression of programmed cell death 5 is associated with chondrosarcoma. (PMID:20872801)
• Lost or reduced PDCD5 expression may contribute to the pathogenesis of human serous cystadenocarcinomas. (PMID:21165576)
• This study is the first providing evidence that PDCD5 plays an important role in cardiac remodeling. (PMID:22253891)
• The effect of recombinant human PDCD5 was also investigated and shown to sensitize cells to DNA damage by promoting caspase-3 activity. (PMID:22261045)
• the PDCD5 binding site on p53 is localized within residues 41-56 of p53 TAD2 subdomain while p53 binds preferentially to the positively charged surface region around the C-terminals of helices alpha3 and alpha5 and the N-terminal of helix alpha4 of PDCD5 (PMID:22372375)
• PDCD5 promotes chemosensitivity by activating the mitochondria-related apoptotic pathway. (PMID:22688731)
• PDCD5 participates in the inflammatory process of asthmatic airway. Its abnormal expression may be associated with the uncontrolled state of asthmatics. (PMID:22883196)
• PDCD5 may contribute to maintain a basal pool of p53 proteins in unstressed conditions, but upon DNA damage it functions as a co-activator of p53 to regulate transcription and cell cycle arrest. (PMID:22914926)
• results suggest that PDCD5 expression plays a significant role in the malignant progression of human gastrointestinal stromal tumors and may be a key inhibitory factor (PMID:22965478)
• Insulin-like growth factor 1 down-regulates programmed cell death 5 in osteoarthritis chondrocytes. (PMID:23322062)
• Plasma and synovial fluid PDCD5 expression levels are inversely associated with TNF-alpha and disease activity in patients with rheumatoid arthritis. (PMID:23327497)
• Data indicate that the expressions of genes PDCD5 and TIMP2 were consistent with their DNA methylation profiles. (PMID:23369618)
• a correlation between increased levels of PDCD5 in serum and liver disease progression and indicate the potential utility of serum PDCD5 as a biomarker for monitoring liver injury. (PMID:23656249)
• Transgenic PDCD5 plays an antitumor role with increased expression, suppressing skin cancer development. (PMID:23688867)
• PDCD5 could be considered as a reliable marker of favorable prognosis of HCC patients (PMID:23807738)
• We confirmed that PDCD5 overexpression stimulated the promoter activities of KLF9 by luciferase reporter assays. (PMID:24173774)
• The expression of PDCD5 and its protein were shown to be reduced in laryngeal squamous cell carcinoma. The functional importance of PDCD5 as a regulating agent in cell apoptosis suggests that it may play a key role in tumour pathogenesis and development. (PMID:24265335)
• PDCD5 is necessary and sufficient for NF-kappaB p65 mediated apoptosis (PMID:24343129)
• PDCD5 bound the apical domain of the CCTbeta subunit, projecting above the folding cavity without entering it. Like PDCD5, beta-tubulin also interacts with the CCTbeta apical domain, but a second site is found at the sensor loop deep within the folding cavity. (PMID:24375412)
• our study describes a new mechanism for p53 stabilization through PDCD5 upon hypoxia or pVHL loss, and reveals new clinical potential for the treatment of pathobiological disorders linked to hypoxic stress (PMID:24469044)
• Authors identified DNAJB1 as a negative regulator of PDCD5-mediated apoptosis and found that the apoptosis network of PDCD5 regulates cancer cell death. (PMID:25444898)
• Findings have uncovered an apoptotic signaling cascade linking PDCD5, OTUD5, and p53 during genotoxic stress responses. (PMID:25499082)
• These findings uncovered an apoptotic signaling cascade linking YAF2, PDCD5, and TP53 during genotoxic stress responses. (PMID:25603536)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pdcd5	ENSDARG00000026072
mus_musculus	Pdcd5	ENSMUSG00000030417
rattus_norvegicus	Pdcd5l1	ENSRNOG00000078933
drosophila_melanogaster	PDCD-5	FBGN0036580
caenorhabditis_elegans	D2005.3	WBGENE00008398

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Saccharolobus islandicus L.S.2.15	C3MR75	100.0%	Diamond
Saccharolobus islandicus M.14.25	C3MXG4	100.0%	Diamond
Saccharolobus islandicus M.16.27	C3MZB0	100.0%	Diamond
Saccharolobus islandicus Y.G.57.14	C3N7D0	100.0%	Diamond
Saccharolobus islandicus M.16.4	C4KII8	100.0%	Diamond
Pongo abelii	Q5RBT0	100.0%	Diamond
Bos taurus	Q2HJH9	96.8%	Diamond
Methanosarcina mazei Go1	Q8PYQ7	94.3%	Diamond
Methanosarcina acetivorans C2A	Q8TIN0	94.3%	Diamond
Saccharolobus islandicus Y.N.15.51	C3NGA4	94.1%	Diamond
Saccharolobus solfataricus P2	Q980F8	94.1%	Diamond
Pyrococcus horikoshii OT3	O58787	93.9%	Diamond
Pyrococcus abyssi GE5	P56813	93.9%	Diamond
Pyrococcus furiosus DSM 3638	Q8U1W7	93.8%	Diamond
Methanococcus maripaludis C7	A6VIE7	91.6%	Diamond
Methanococcus maripaludis S2	Q6M0W1	91.6%	Diamond
Methanosarcina barkeri str. Fusaro	Q46FA5	91.0%	Diamond
Methanococcus maripaludis C5	A4G031	90.8%	Diamond
Thermococcus onnurineus NA1	B6YWX7	90.2%	Diamond
Thermococcus gammatolerans EJ3	C5A636	90.2%	Diamond
Thermococcus kodakarensis KOD1	Q5JGN3	89.3%	Diamond
Pyrobaculum islandicum DSM 4184	A1RRN7	89.1%	Diamond
Pyrobaculum arsenaticum DSM 13514	A4WLS5	89.1%	Diamond
Pyrobaculum neutrophilum V24Sta	B1YAF2	88.2%	Diamond
Pyrobaculum aerophilum str. IM2	Q8ZTX7	88.2%	Diamond
Sulfolobus acidocaldarius DSM 639	Q4J8U0	86.6%	Diamond
Sulfurisphaera tokodaii str. 7	Q971I0	86.6%	Diamond
Thermococcus sibiricus MM 739	C6A1U6	81.3%	Diamond
Thermoplasma volcanium GSS1	Q97CU3	74.8%	Diamond
Thermoplasma acidophilum DSM 1728	Q9HM19	74.8%	Diamond
Methanococcus aeolicus Nankai-3	A6UVQ4	71.1%	Diamond
Methanoregula boonei 6A8	A7I9J0	69.6%	Diamond
Methanosphaerula palustris E1-9c	B8GEU2	69.6%	Diamond
Methanospirillum hungatei JF-1	Q2FTJ7	67.9%	Diamond
Archaeoglobus fulgidus DSM 4304	O28211	65.6%	Diamond
Methanothrix thermoacetophila PT	A0B9G7	65.1%	Diamond
Methanococcoides burtonii DSM 6242	Q12ZJ1	64.6%	Diamond
Methanocaldococcus jannaschii DSM 2661	Q58103	63.5%	Diamond
Thermofilum pendens Hrk 5	A1RXF0	63.3%	Diamond
Picrophilus oshimae DSM 9789	Q6L2L3	63.2%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
SNORA68B	snoRNA	109616972
RGS9BP	protein-coding	388531
ANKRD27	protein-coding	84079
DPY19L3	protein-coding	147991
DPY19L3-DT	ncRNA	400684
ZNF507	protein-coding	22847
NUDT19-DT	ncRNA	118827810
NUDT19	protein-coding	390916

Protein

Protein identifiers

Programmed cell death protein 5 — O14737 (reviewed: O14737)

Alternative names: TF-1 cell apoptosis-related protein 19

All UniProt accessions (5): O14737, K7EQA1, K7ESJ4, Q3HM38, X6R2P6

UniProt curated annotations — full annotation on UniProt →

Function. In response to DNA damage, associates with TP53/p53 to prevent MDM2-mediated degradation of TP53 and promote TP53-mediated signaling. Also protects KAT5/TIP60 from degradation, which further promotes TP53/p53-mediated signaling.

Subunit / interactions. Interacts (via N-terminus) with PPEF1; the interaction is direct, and leads to dephosphorylation of PDCD5 at Ser-119, PDCD5 destabilization, and downstream inhibition of TP53/p53-mediated signaling. Interacts with TP53; the interaction is direct and prevents the interaction between TP53 and MDM2, thereby stabilizing TP53. Interacts with KAT5/TIP60; the interaction is direct and leads to stabilization of the KAT5 protein.

Subcellular location. Nucleus. Cytoplasm. Cytosol.

Tissue specificity. Widely expressed. Highest levels in heart, testis, kidney, pituitary gland, adrenal gland and placenta.

Post-translational modifications. Phosphorylated at Ser-119 by casein kinase II. Dephosphorylated at Ser-119 by PPEF1, which promotes its degradation by the proteasome.

Induction. Induced in response to DNA damage (at protein level).

Similarity. Belongs to the PDCD5 family.

Isoforms (2)

UniProt ID	Names	Canonical?
O14737-1	1	yes
O14737-2	2

RefSeq proteins (1): NP_004699* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002836	PDCD5-like	Family
IPR036883	PDCD5-like_sf	Homologous_superfamily

Pfam: PF01984

UniProt features (16 total): helix 5, modified residue 4, region of interest 2, initiator methionine 1, chain 1, strand 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

3 structures by resolution:

PDB	Title	Method	Resolution (Å)
1YYB	Solution structure of 1-26 fragment of human programmed cell death 5 protein	SOLUTION NMR
2CRU	Solution structure of programmed cell death 5	SOLUTION NMR
2K6B	Solution structure of 1-112 fragment of human programmed cell death 5 protein	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14737-F1	75.13	0.05

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; nucleoplasm

Antibody reliability (HPA): IH enhanced · IF approved

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 (4)

Type	Positions
N-acetylalanine	2
Phosphoserine	51, 119
N6-acetyllysine	63

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 147 (showing top): HONMA_DOCETAXEL_RESISTANCE, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, DARWICHE_SKIN_TUMOR_PROMOTER_UP, DARWICHE_PAPILLOMA_RISK_LOW_UP, DARWICHE_PAPILLOMA_RISK_HIGH_UP, KYNG_DNA_DAMAGE_DN, DARWICHE_SQUAMOUS_CELL_CARCINOMA_UP, GOBP_PROTEIN_MATURATION, KYNG_ENVIRONMENTAL_STRESS_RESPONSE_NOT_BY_GAMMA_IN_WS, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, GOBP_RESPONSE_TO_TRANSFORMING_GROWTH_FACTOR_BETA, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_13, GOBP_PROTEIN_FOLDING, GARY_CD5_TARGETS_DN

GO Biological Process (9): apoptotic process (GO:0006915), positive regulation of gene expression (GO:0010628), regulation of apoptotic process (GO:0042981), positive regulation of apoptotic process (GO:0043065), cellular response to transforming growth factor beta stimulus (GO:0071560), negative regulation of protein folding (GO:1903333), T cell activation (GO:0042110), positive regulation of signal transduction by p53 class mediator (GO:1901798), positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator (GO:1902255)

GO Molecular Function (6): DNA binding (GO:0003677), heparin binding (GO:0008201), acetyltransferase activator activity (GO:0010698), beta-tubulin binding (GO:0048487), protein binding (GO:0005515), protein sequestering activity (GO:0140311)

GO Cellular Component (4): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), extracellular exosome (GO:0070062)

GO top-level categories

37 GO namespaces:

Category	Terms
apoptotic process	2
cellular anatomical structure	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
regulation of programmed cell death	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
cellular response to growth factor stimulus	1
response to transforming growth factor beta	1
protein folding	1
negative regulation of cellular process	1
regulation of protein folding	1
lymphocyte activation	1
signal transduction by p53 class mediator	1
regulation of signal transduction by p53 class mediator	1
positive regulation of intracellular signal transduction	1
intrinsic apoptotic signaling pathway by p53 class mediator	1
positive regulation of signal transduction by p53 class mediator	1
regulation of intrinsic apoptotic signaling pathway by p53 class mediator	1
positive regulation of intrinsic apoptotic signaling pathway	1
nucleic acid binding	1
glycosaminoglycan binding	1
sulfur compound binding	1
enzyme activator activity	1
acetyltransferase activity	1
tubulin binding	1
binding	1
protein binding	1
molecular sequestering activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
extracellular vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 11 of 19 annotations. The rest are phylogenetic / computational / electronic (IEA).

11 experimentally-supported GO terms:

GO term	NS	Evidence
cellular response to transforming growth factor beta stimulus	BP	direct assay
negative regulation of protein folding	BP	mutant phenotype
positive regulation of apoptotic process	BP	mutant phenotype
positive regulation of gene expression	BP	direct assay
regulation of apoptotic process	BP	mutant phenotype
cytoplasm	CC	high-throughput assay
extracellular exosome	CC	high-throughput assay
nucleus	CC	direct assay
acetyltransferase activator activity	MF	direct assay
beta-tubulin binding	MF	physical interaction
heparin binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 2,074 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PDCD5	CSF2	P04141	607
PDCD5	YAF2	Q8IY57	421
PDCD5	OTUD5	Q96G74	403
PDCD5	DEF8	Q6ZN54	370
PDCD5	MTHFSD	Q2M296	370
PDCD5	WDR12	Q9GZL7	365
PDCD5	IK	Q13123	365
PDCD5	CDC6	Q99741	361
PDCD5	OSTF1	Q92882	360
PDCD5	FANK1	Q8TC84	360
PDCD5	TMBIM6	P55061	357
PDCD5	PDCD2	Q16342	354
PDCD5	TP53	P04637	346
PDCD5	DNAJB1	P25685	331
PDCD5	RALY	Q9UKM9	323

IntAct

Human interaction partners of PDCD5 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 32 partners by confidence:

Partner	Interaction type	MIscore	Records
PICK1	physical association	0.560	3
RAD18	physical association	0.560	3
TRIM35	physical association	0.560	3
CCT3	association	0.530	1
KDM1A	physical association	0.370	1
NUDT3	physical association	0.370	1
UBE2D3	physical association	0.370	1
CCT4	association	0.350	1
CCT5	association	0.350	1
CCT7	association	0.350	1
CCT8	association	0.350	1
CDK10	association	0.350	1
FBXW8	association	0.350	1
PDCL3	association	0.350	1
PKDCC	association	0.350	1
TCEAL1	association	0.350	1
TSSK3	association	0.350	1
TUBG1	association	0.350	1
ZNF248	association	0.350	1
ZNF695	association	0.350	1
ACP5	physical association	0.000	1
CEP126	physical association	0.000	1
EEF1G	physical association	0.000	1
EIF1B	physical association	0.000	1
HLA-B	physical association	0.000	1
IKBKE	physical association	0.000	1
KAT5	physical association	0.000	1
MCC	physical association	0.000	1
RIF1	physical association	0.000	1
TNIK	physical association	0.000	1

BioGRID (148 interactions; top human partners by supporting records): TP53 (Affinity Capture-Western; 7 records), CCT3 (Affinity Capture-MS; 5 records), CCT4 (Affinity Capture-MS; 5 records), OTUD5 (Affinity Capture-Western; 5 records), TCP1 (Cross-Linking-MS (XL-MS); 4 records), KAT5 (Two-hybrid; 3 records), VHL (Affinity Capture-MS; 3 records), CCNF (Proximity Label-MS; 2 records), CCT2 (Affinity Capture-MS; 2 records), CCT8 (Affinity Capture-MS; 2 records), KRAS (Negative Genetic; 2 records), MAPT (Proximity Label-MS; 2 records), TIPARP (Affinity Capture-MS; 2 records), TUBG1 (Affinity Capture-MS; 2 records), YAF2 (Affinity Capture-Western; 2 records)

SIGNOR signaling

2 signaling interactions:

A	Effect	B	Mechanism
CSNK2A1	up-regulates	PDCD5	phosphorylation
PPEF1	“down-regulates quantity by destabilization”	PDCD5	dephosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 32 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
Formation of tubulin folding intermediates by CCT/TriC	5	92.0×	9e-08
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	5	88.7×	9e-08
Prefoldin mediated transfer of substrate to CCT/TriC	5	85.6×	9e-08
Chaperonin-mediated protein folding	5	65.3×	2e-07
Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding	5	65.3×	2e-07
Association of TriC/CCT with target proteins during biosynthesis	5	63.7×	2e-07
Protein folding	5	56.4×	4e-07
Cilium Assembly	5	23.6×	3e-05

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of telomere maintenance via telomerase	5	118.2×	4e-08
binding of sperm to zona pellucida	5	68.0×	6e-07
protein folding	6	20.0×	2e-05
protein stabilization	7	15.1×	1e-05

Disease & clinical

Genetic variants

Variant evidence for PDCD5: 26 ClinVar records (0 pathogenic / likely pathogenic); 21 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	14
Likely benign	0
Benign	2

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 32 predictions of 572):

Position(s)	Effect	Δscore	Sites
19:32581328–32581329	donor_loss	1.0000	3
19:32586846	acceptor_gain	1.0000
19:32586987	donor_gain	1.0000
19:32581328	donor_loss	0.9900	2
19:32582233–32582234	donor_loss	0.9900	5
19:32582338	acceptor_gain	0.9900
19:32586847	acceptor_gain	0.9900
19:32586856–32586857	acceptor_loss	0.9900	6
19:32587251–32587252	acceptor_loss	0.9900	6
19:32582193–32582194	acceptor_loss	0.9800	6

AlphaMissense

262 missense substitutions predicted likely pathogenic (of 823 scored), across 86 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D118	8	0.656	0.866
R55	7	0.954	0.986
E71	7	0.851	0.972
R10	6	0.954	0.979
R13	6	0.949	0.973
F111	6	0.929	0.991
R113	6	0.929	0.987
V109	6	0.896	0.965
M77	6	0.805	0.848
R114	5	0.941	0.978
L96	5	0.896	0.991
G81	5	0.865	0.976
K63	5	0.853	0.869
E89	5	0.836	0.948
N58	5	0.830	0.918
V62	5	0.819	0.966
K66	5	0.805	0.865
V70	5	0.779	0.981
R40	5	0.750	0.896
K86	5	0.748	0.875

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

6 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	unfavorable	3.17e-10
Kidney Renal Papillary Cell Carcinoma (TCGA)	unfavorable	3.13e-08
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	2.76e-06
Kidney Renal Clear Cell Carcinoma (validation)	unfavorable	1.23e-05
Liver Hepatocellular Carcinoma (validation)	unfavorable	3.03e-05
Lung Adenocarcinoma (TCGA)	unfavorable	0.000146

Disease associations

OMIM: gene MIM:604583 | disease phenotypes:

GWAS associations

21 associations:

Study	Trait	p-value
GCST90002395_318	Mean platelet volume	6e-30
GCST90002390_3	Mean corpuscular hemoglobin	4e-27
GCST90002404_550	Red cell distribution width	1e-25
GCST004630_189	Mean corpuscular hemoglobin	4e-22
GCST90002392_131	Mean corpuscular volume	2e-21
GCST90002392_130	Mean corpuscular volume	3e-21
GCST90002387_16	Immature fraction of reticulocytes	3e-19
GCST004630_188	Mean corpuscular hemoglobin	1e-17
GCST90002397_796	Mean spheric corpuscular volume	1e-17
GCST004602_145	Mean corpuscular volume	2e-17
GCST90002402_401	Platelet count	2e-17
GCST90002390_4	Mean corpuscular hemoglobin	3e-15
GCST90002396_484	Mean reticulocyte volume	1e-14
GCST90002397_795	Mean spheric corpuscular volume	9e-14
GCST90002396_483	Mean reticulocyte volume	7e-13
GCST90002391_238	Mean corpuscular hemoglobin concentration	1e-11
GCST004621_12	Red cell distribution width	3e-10
GCST011956_224	Systemic lupus erythematosus	5e-10
GCST004599_91	Mean platelet volume	3e-9
GCST001850_6	Major depressive disorder	7e-7
GCST009391_1719	Metabolite levels	8e-6

EFO canonical traits (from GWAS)

6 canonical traits:

EFO ID	Trait name
EFO:0009188	Red cell distribution width
EFO:0004527	mean corpuscular hemoglobin
EFO:0007787	plasma betaine measurement
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0010701	mean reticulocyte volume
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066424 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression	4
bisphenol A	decreases expression, increases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
arsenite	affects binding, increases reaction, increases methylation	2
beauvericin	increases expression	1
deoxynivalenol	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization, increases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
avobenzone	increases expression	1
pentabromodiphenyl ether	increases expression	1
CGP 52608	affects binding, increases reaction	1
pluronic block copolymer p85	affects cotreatment, increases expression	1
motexafin gadolinium	decreases expression, affects cotreatment	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
10’(Z),13’(E),15’(E)-heptadecatrienylhydroquinone	increases expression	1
bisphenol B	increases expression	1
quinocetone	decreases expression, increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic Trioxide	increases expression	1
Vorinostat	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Atrazine	increases expression	1
Calcitriol	decreases expression	1
Cisplatin	increases response to substance	1
Demecolcine	decreases 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
CHEMBL5651996	Binding	Binding affinity to human PDCD5 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*

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9MF	Ubigene HEK293 PDCD5 KO	Transformed cell line	Female
CVCL_TC62	HAP1 PDCD5 (-) 1	Cancer cell line	Male
CVCL_XR46	HAP1 PDCD5 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for PDCD5 across ~30M SureChEMBL compounds — explore on Sugi Predict.