DEDD

Summary

DEDD (death effector domain containing, HGNC:2755) is a protein-coding gene on chromosome 1q23.3, encoding Death effector domain-containing protein (O75618). A scaffold protein that directs CASP3 to certain substrates and facilitates their ordered degradation during apoptosis.

This gene encodes a protein that contains a death effector domain (DED). DED is a protein-protein interaction domain shared by adaptors, regulators and executors of the programmed cell death pathway. Overexpression of this gene was shown to induce weak apoptosis. Upon stimulation, this protein was found to translocate from cytoplasm to nucleus and colocalize with UBTF, a basal factor required for RNA polymerase I transcription, in the nucleolus. At least three transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 9191 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 41 total
• MANE Select transcript: NM_032998

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2755
Approved symbol	DEDD
Name	death effector domain containing
Location	1q23.3
Locus type	gene with protein product
Status	Approved
Aliases	DEFT, FLDED1, CASP8IP1, KE05, DEDD1
Ensembl gene	ENSG00000158796
Ensembl biotype	protein_coding
OMIM	606841
Entrez	9191

Gene structure

Transcript identifiers

Ensembl transcripts: 58 — 52 protein_coding, 6 protein_coding_CDS_not_defined

ENST00000368005, ENST00000368006, ENST00000458050, ENST00000463227, ENST00000464113, ENST00000472996, ENST00000473679, ENST00000486041, ENST00000489249, ENST00000490843, ENST00000496632, ENST00000545495, ENST00000865101, ENST00000865102, ENST00000865103, ENST00000865104, ENST00000865105, ENST00000865106, ENST00000865107, ENST00000865108, ENST00000865109, ENST00000865110, ENST00000865111, ENST00000865112, ENST00000865113, ENST00000865114, ENST00000865115, ENST00000865116, ENST00000865117, ENST00000865118, ENST00000865119, ENST00000935444, ENST00000935445, ENST00000935446, ENST00000935447, ENST00000935448, ENST00000935449, ENST00000935450, ENST00000935451, ENST00000935452, ENST00000935453, ENST00000935454, ENST00000935455, ENST00000935456, ENST00000935457, ENST00000935458, ENST00000935459, ENST00000935460, ENST00000935461, ENST00000935462, ENST00000935463, ENST00000935464, ENST00000935465, ENST00000943065, ENST00000943066, ENST00000943067, ENST00000943068, ENST00000943069

RefSeq mRNA: 4 — MANE Select: NM_032998 NM_001039711, NM_001039712, NM_001330765, NM_032998

CCDS: CCDS1219, CCDS81391

Canonical transcript exons

ENST00000368006 — 6 exons

Exon	Start	End
ENSE00001041055	161130815	161130847
ENSE00001814340	161132551	161132667
ENSE00001872364	161120974	161122523
ENSE00003704178	161123075	161123221
ENSE00003707360	161124138	161124526
ENSE00003711274	161123839	161123946

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 94.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.6358 / max 61.5245, expressed in 1804 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15594	7.2422	1753
15595	3.8086	1628
15593	2.2061	1365
15596	0.3788	191

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	94.49	gold quality
gastrocnemius	UBERON:0001388	94.09	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.02	gold quality
mucosa of stomach	UBERON:0001199	93.99	gold quality
secondary oocyte	CL:0000655	93.90	gold quality
muscle of leg	UBERON:0001383	93.64	gold quality
gall bladder	UBERON:0002110	93.49	gold quality
blood	UBERON:0000178	93.40	gold quality
muscle organ	UBERON:0001630	93.19	gold quality
granulocyte	CL:0000094	93.10	gold quality
right coronary artery	UBERON:0001625	93.09	gold quality
omental fat pad	UBERON:0010414	92.93	gold quality
peritoneum	UBERON:0002358	92.92	gold quality
biceps brachii	UBERON:0001507	92.83	gold quality
adipose tissue of abdominal region	UBERON:0007808	92.82	gold quality
popliteal artery	UBERON:0002250	92.70	gold quality
monocyte	CL:0000576	92.69	gold quality
tibial artery	UBERON:0007610	92.69	gold quality
stromal cell of endometrium	CL:0002255	92.64	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	92.60	gold quality
upper arm skin	UBERON:0004263	92.57	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	92.53	gold quality
mononuclear cell	CL:0000842	92.51	gold quality
leukocyte	CL:0000738	92.48	gold quality
left uterine tube	UBERON:0001303	92.45	gold quality
lower esophagus muscularis layer	UBERON:0035833	92.41	gold quality
lower esophagus	UBERON:0013473	92.39	gold quality
skeletal muscle tissue	UBERON:0001134	92.31	gold quality
ganglionic eminence	UBERON:0004023	92.24	gold quality
subcutaneous adipose tissue	UBERON:0002190	92.21	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.52

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
CFLAR	Unknown
FADD	Unknown

Literature-anchored findings (GeneRIF, showing 6)

• DEDD forms nuclear complexes with the TFIIIC102 subunit of human transcription factor IIIC (PMID:11965497)
• DEDD and DEDD2 may be important mediators for death receptors and that they may target caspases to the nucleus. (PMID:12527898)
• FAS-associated death domain (FADD)-DED-induced reactive oxygen species (ROS) generation is triggered by membrane localization of FADD-DED, which shifts the cells into a state that stimulates and fuels ROS and ultimately results in cell death. (PMID:20070122)
• Via direct interaction with the class III PI-3-kinase (PI3KC3)/Beclin1, DEDD activated autophagy and induced the degradation of Snail and Twist, two master regulators of EMT (PMID:22719072)
• MicroRNA-17 inhibition overcomes chemoresistance and suppresses epithelial-mesenchymal transition through a DEDD-dependent mechanism in gastric cancer (PMID:29953965)
• Identify MCL1 and DEDD as genes that contribute to aggressive urothelial carcinomas. (PMID:30777879)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	dedd	ENSDARG00000029783
mus_musculus	Dedd	ENSMUSG00000013973
rattus_norvegicus	Dedd	ENSRNOG00000003779

Paralogs (1): DEDD2 (ENSG00000160570)

Protein

Protein identifiers

Death effector domain-containing protein — O75618 (reviewed: O75618)

Alternative names: DEDPro1, Death effector domain-containing testicular molecule, FLDED-1

All UniProt accessions (3): B1AQP5, O75618, V9GY27

UniProt curated annotations — full annotation on UniProt →

Function. A scaffold protein that directs CASP3 to certain substrates and facilitates their ordered degradation during apoptosis. May also play a role in mediating CASP3 cleavage of KRT18. Regulates degradation of intermediate filaments during apoptosis. May play a role in the general transcription machinery in the nucleus and might be an important regulator of the activity of GTF3C3. Inhibits DNA transcription in vitro.

Subunit / interactions. Interacts with CASP8, CASP10, KRT8, KRT18, CASP3 and FADD. Homodimerizes and heterodimerizes with DEDD2.

Subcellular location. Cytoplasm. Nucleus. Nucleolus.

Tissue specificity. Widely expressed with highest levels in testis.

Post-translational modifications. Exists predominantly in a mono- or diubiquitinated form.

Isoforms (2)

UniProt ID	Names	Canonical?
O75618-1	1	yes
O75618-2	2

RefSeq proteins (4): NP_001034800, NP_001034801, NP_001317694, NP_127491* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001875	DED_dom	Domain
IPR011029	DEATH-like_dom_sf	Homologous_superfamily
IPR038856	DEDD/DEDD2	Family
IPR049341	TRADD-like_N	Domain

Pfam: PF01335, PF20694

UniProt features (5 total): region of interest 2, chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75618-F1	77.90	0.52

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 173 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_MALE_GAMETE_GENERATION, FOXO1_01, GGGTGGRR_PAX4_03, BONCI_TARGETS_OF_MIR15A_AND_MIR16_1, GOBP_RRNA_TRANSCRIPTION, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_DECIDUALIZATION, ACCAATC_MIR509, GOBP_APOPTOTIC_SIGNALING_PATHWAY, GOBP_REGULATION_OF_CATABOLIC_PROCESS, AAAGACA_MIR511

GO Biological Process (8): spermatogenesis (GO:0007283), extrinsic apoptotic signaling pathway via death domain receptors (GO:0008625), negative regulation of protein catabolic process (GO:0042177), regulation of apoptotic process (GO:0042981), decidualization (GO:0046697), negative regulation of transcription of nucleolar large rRNA by RNA polymerase I (GO:1901837), developmental process involved in reproduction (GO:0003006), apoptotic process (GO:0006915)

GO Molecular Function (2): DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (3): nucleolus (GO:0005730), cytoplasm (GO:0005737), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
developmental process involved in reproduction	2
male gamete generation	1
extrinsic apoptotic signaling pathway	1
negative regulation of catabolic process	1
protein catabolic process	1
regulation of protein catabolic process	1
negative regulation of protein metabolic process	1
apoptotic process	1
regulation of programmed cell death	1
maternal placenta development	1
tissue development	1
negative regulation of transcription by RNA polymerase I	1
nucleolar large rRNA transcription by RNA polymerase I	1
regulation of transcription of nucleolar large rRNA by RNA polymerase I	1
reproductive process	1
developmental process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
nucleic acid binding	1
binding	1
nuclear lumen	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

712 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DEDD	ERI1	Q8IV48	882
DEDD	BECN1	Q14457	870
DEDD	SLBP	Q14493	785
DEDD	CASP3	P42574	693
DEDD	RNF34	Q969K3	681
DEDD	CNOT6	Q9ULM6	667
DEDD	PIK3C3	Q8NEB9	650
DEDD	CNOT8	Q9UFF9	626
DEDD	CNOT7	Q9UIV1	617
DEDD	CNOT6L	Q96LI5	610
DEDD	PARN	O95453	607
DEDD	KRT18	P05783	603
DEDD	KRT8	P05787	600
DEDD	CNOT9	Q92600	590
DEDD	NIT1	Q86X76	579

IntAct

36 interactions, top by confidence:

A	B	Type	Score
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
SKP1	MYCBP2	psi-mi:“MI:0914”(association)	0.640
ATXN7L3	USP27X	psi-mi:“MI:0914”(association)	0.640
DNAJC3	DEDD	psi-mi:“MI:0914”(association)	0.530
APLP2	DEDD	psi-mi:“MI:0915”(physical association)	0.520
DEDD	SMAD3	psi-mi:“MI:0915”(physical association)	0.400
HOXD4	DEDD	psi-mi:“MI:0915”(physical association)	0.370
BATF2	DEDD	psi-mi:“MI:0915”(physical association)	0.370
SHMT1	DEDD	psi-mi:“MI:0915”(physical association)	0.370
CDK1	DEDD	psi-mi:“MI:0914”(association)	0.350
USP22	CNOT1	psi-mi:“MI:0914”(association)	0.350
SKP1	BHLHE40	psi-mi:“MI:0914”(association)	0.350
RBX1	OBSL1	psi-mi:“MI:0914”(association)	0.350
CHAF1B	KDM4A	psi-mi:“MI:0914”(association)	0.350
SKP1	RNASET2	psi-mi:“MI:0914”(association)	0.350
SKP1	NDUFAB1	psi-mi:“MI:0914”(association)	0.350
CFTR	UBA6	psi-mi:“MI:2364”(proximity)	0.270
DEDD	RANBP3	psi-mi:“MI:0915”(physical association)	0.000
DEDD	KHK	psi-mi:“MI:0915”(physical association)	0.000
DEDD	CCDC59	psi-mi:“MI:0915”(physical association)	0.000
SERPINI1	DEDD	psi-mi:“MI:0915”(physical association)	0.000
DEDD	ATP6V1E1	psi-mi:“MI:0915”(physical association)	0.000
DEDD	LTV1	psi-mi:“MI:0915”(physical association)	0.000
DEDD	TCEAL5	psi-mi:“MI:0915”(physical association)	0.000
DEDD	APLP2	psi-mi:“MI:0915”(physical association)	0.000
APLP2	DEDD	psi-mi:“MI:0915”(physical association)	0.000
DEDD	RSRC2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (46): DEDD (Affinity Capture-RNA), DEDD (Affinity Capture-RNA), DEDD (Reconstituted Complex), DEDD (Affinity Capture-RNA), RANBP3 (Affinity Capture-MS), KHK (Affinity Capture-MS), CCDC59 (Affinity Capture-MS), DEDD (Proximity Label-MS), DEDD (Affinity Capture-Western), DEDD (Affinity Capture-Western), DEDD (Affinity Capture-Western), DEDD (Affinity Capture-MS), DEDD (Affinity Capture-MS), DEDD (Affinity Capture-MS), DEDD (Affinity Capture-Western)

ESM2 similar proteins: A0A1B0GVV1, A0PJX4, A3KN28, A6QNZ8, B5DEK8, O73612, O75618, O88942, P01134, P01344, P07456, P10764, P48030, P51459, P52799, P52800, P98172, Q0V9A8, Q0VBP7, Q2YDG0, Q3KRC4, Q3SXP7, Q5E943, Q5HZN7, Q5JRV8, Q5PQS5, Q5R8M2, Q5RDG5, Q5RDV6, Q5XGS4, Q5ZIS9, Q68FW3, Q7TMP6, Q8BGZ2, Q8BH32, Q8BHW5, Q8CA71, Q8K3J9, Q8K4P7, Q8R092

Diamond homologs: O75618, Q8QZV0, Q8WXF8, Q9Z1L3, Q9Z2K0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 38 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
protein ubiquitination	6	7.3×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	29
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1056 predictions. Top by Δscore:

Variant	Effect	Δscore
1:161122521:TGT:T	acceptor_gain	1.0000
1:161122522:GTC:G	acceptor_loss	1.0000
1:161122523:TCTG:T	acceptor_loss	1.0000
1:161122524:C:CC	acceptor_gain	1.0000
1:161122527:T:TC	acceptor_gain	1.0000
1:161122534:C:CT	acceptor_gain	1.0000
1:161122535:A:T	acceptor_gain	1.0000
1:161123068:T:TA	donor_gain	1.0000
1:161123833:TCTCA:T	donor_loss	1.0000
1:161123834:CTCAC:C	donor_loss	1.0000
1:161123835:TCA:T	donor_loss	1.0000
1:161123836:CA:C	donor_loss	1.0000
1:161123838:C:CA	donor_loss	1.0000
1:161123942:GCACA:G	acceptor_gain	1.0000
1:161123943:CACA:C	acceptor_gain	1.0000
1:161123943:CACAC:C	acceptor_gain	1.0000
1:161123944:ACA:A	acceptor_gain	1.0000
1:161123945:CA:C	acceptor_gain	1.0000
1:161123945:CACTG:C	acceptor_gain	1.0000
1:161123947:C:CC	acceptor_gain	1.0000
1:161124131:T:TA	donor_gain	1.0000
1:161124136:ACCAG:A	donor_gain	1.0000
1:161124137:CCAGC:C	donor_gain	1.0000
1:161124312:C:CT	acceptor_gain	1.0000
1:161124313:A:T	acceptor_gain	1.0000
1:161124315:C:CT	acceptor_gain	1.0000
1:161130868:A:T	acceptor_gain	1.0000
1:161130871:A:T	acceptor_gain	1.0000
1:161130878:C:CT	acceptor_gain	1.0000
1:161130879:A:T	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000079342 (1:161128461 C>A,T), RS1000153866 (1:161132967 G>A), RS1000495381 (1:161131529 G>A), RS1000893680 (1:161121235 C>A,T), RS1001560087 (1:161124615 G>A), RS1001596000 (1:161124893 C>T), RS1001725631 (1:161124025 A>G), RS1001734260 (1:161131875 A>G), RS1001895572 (1:161122829 C>T), RS1001988211 (1:161124519 C>T), RS1002504655 (1:161128039 T>C), RS1002598890 (1:161126451 C>T), RS1002831101 (1:161129822 A>G), RS1003750682 (1:161128377 G>A), RS1003803242 (1:161131230 G>A)

Disease associations

OMIM: gene MIM:606841 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases methylation	2
FR900359	increases phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
abrine	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Irinotecan	decreases expression	1
Rosiglitazone	increases expression	1
Amiodarone	increases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases expression	1
Catechin	increases expression, affects cotreatment	1
Doxorubicin	decreases expression	1
Drugs, Chinese Herbal	increases expression	1
Naphthoquinones	increases expression	1
Nicotine	decreases expression	1
Selenium	increases expression	1
Silicon Dioxide	decreases expression	1
Thiram	decreases expression	1
Vitamin E	increases expression	1
2-Naphthylamine	increases expression	1
Aflatoxin B1	increases methylation	1
Paclitaxel	decreases expression	1

Clinical trials (associated diseases)

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