DDIAS

Summary

DDIAS (DNA damage induced apoptosis suppressor, HGNC:26351) is a protein-coding gene on chromosome 11q14.1, encoding DNA damage-induced apoptosis suppressor protein (Q8IXT1). May be an anti-apoptotic protein involved in DNA repair or cell survival.

Involved in negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage and regulation of DNA stability. Predicted to be active in cytoplasm and nucleus.

Source: NCBI Gene 220042 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 135 total
• MANE Select transcript: NM_145018

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26351
Approved symbol	DDIAS
Name	DNA damage induced apoptosis suppressor
Location	11q14.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ38838, FLJ25416, noxin
Ensembl gene	ENSG00000165490
Ensembl biotype	protein_coding
OMIM	618045
Entrez	220042

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 19 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000329143, ENST00000524921, ENST00000525361, ENST00000525388, ENST00000528189, ENST00000528262, ENST00000528759, ENST00000532277, ENST00000532589, ENST00000532764, ENST00000533655, ENST00000533750, ENST00000930241, ENST00000930242, ENST00000930243, ENST00000930244, ENST00000930245, ENST00000930246, ENST00000930247, ENST00000930248, ENST00000930249

RefSeq mRNA: 2 — MANE Select: NM_145018 NM_001363481, NM_145018

CCDS: CCDS8263

Canonical transcript exons

ENST00000533655 — 6 exons

Exon	Start	End
ENSE00002159602	82931732	82934659
ENSE00002173930	82901736	82901822
ENSE00002186681	82913287	82913386
ENSE00003528572	82914723	82914851
ENSE00003595186	82928777	82928938
ENSE00003625158	82930157	82930274

Expression profiles

Bgee: expression breadth ubiquitous, 167 present calls, max score 93.62.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.7667 / max 66.4794, expressed in 1097 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
116051	4.7667	1097

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	93.62	gold quality
secondary oocyte	CL:0000655	93.58	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.61	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.76	gold quality
monocyte	CL:0000576	81.79	gold quality
leukocyte	CL:0000738	81.35	gold quality
ventricular zone	UBERON:0003053	80.69	gold quality
ganglionic eminence	UBERON:0004023	79.42	gold quality
bone marrow cell	CL:0002092	76.07	gold quality
ileal mucosa	UBERON:0000331	74.94	gold quality
bone marrow	UBERON:0002371	74.25	gold quality
granulocyte	CL:0000094	73.66	gold quality
testis	UBERON:0000473	71.09	gold quality
vermiform appendix	UBERON:0001154	70.86	gold quality
right testis	UBERON:0004534	70.59	gold quality
palpebral conjunctiva	UBERON:0001812	70.28	gold quality
esophagus mucosa	UBERON:0002469	69.43	gold quality
left testis	UBERON:0004533	69.20	gold quality
lymph node	UBERON:0000029	69.16	gold quality
stromal cell of endometrium	CL:0002255	69.12	gold quality
esophagus squamous epithelium	UBERON:0006920	69.01	silver quality
trabecular bone tissue	UBERON:0002483	68.86	gold quality
cortical plate	UBERON:0005343	68.69	gold quality
rectum	UBERON:0001052	68.45	gold quality
epithelium of nasopharynx	UBERON:0001951	67.41	silver quality
lower esophagus mucosa	UBERON:0035834	66.66	gold quality
smooth muscle tissue	UBERON:0001135	66.60	gold quality
islet of Langerhans	UBERON:0000006	66.30	gold quality
blood	UBERON:0000178	66.08	gold quality
upper arm skin	UBERON:0004263	65.75	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	5.69

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

54 targeting DDIAS, 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-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687

Literature-anchored findings (GeneRIF, showing 6)

• NOXIN overexpression, as a result of genomic DNA gain or amplification, promotes HCC tumorigenesis by accelerating DNA synthesis and cell cycle progression, where NOXIN functions as a cofactor of DNA polymerase-primase complex (PMID:25612832)
• DDIAS is a target of NFATc1 and is associated with cisplatin resistance in lung cancer cells. (PMID:26493727)
• EGF activates the ERK5/MEF2 pathway, which in turn induces DDIAS expression to promote cancer cell invasion by activating beta-catenin target genes (PMID:27412911)
• these findings indicate that the stability of the DDIAS protein is regulated by CHIP/HSP70-mediated proteasomal degradation and that CHIP overexpression stimulates the apoptosis of lung cancer cells in response to DNA-damaging agents (PMID:28079882)
• Noxin facilitated the expression of Cyclin D1 and Cyclin E1 through activating P38-activating transcription factor 2 signaling pathway, thus enhanced cell growth of breast cancer (PMID:28618963)
• High DDIAS expression suppresses TRAIL-mediated apoptosis by inhibiting DISC formation and destabilizing caspase-8 in lung and liver cancer. (PMID:29242605)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ddias	ENSMUSG00000030641
rattus_norvegicus	Ddias	ENSRNOG00000022521

Protein

Protein identifiers

DNA damage-induced apoptosis suppressor protein — Q8IXT1 (reviewed: Q8IXT1)

Alternative names: Nitric oxide-inducible gene protein

All UniProt accessions (7): B4DS54, E9PLJ5, E9PM93, E9PMA7, E9PN94, E9PQP9, Q8IXT1

UniProt curated annotations — full annotation on UniProt →

Function. May be an anti-apoptotic protein involved in DNA repair or cell survival.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Highly expressed in colorectal and lung cancer tissues.

Induction. Induced by UV irradiation. Expression starts to increase in early S phase and is steady high until late S phase in both cancer and normal cells.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IXT1-1	1	yes
Q8IXT1-2	2

RefSeq proteins (2): NP_001350410, NP_659455* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012340	NA-bd_OB-fold	Homologous_superfamily
IPR013955	Rep_factor-A_C	Domain
IPR043522	DDIAS	Family

Pfam: PF08646

UniProt features (11 total): sequence variant 5, splice variant 2, chain 1, region of interest 1, sequence conflict 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IXT1-F1	43.31	0.07

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 162 (showing top): CCAWYNNGAAR_UNKNOWN, MIDORIKAWA_AMPLIFIED_IN_LIVER_CANCER, GOBP_NEGATIVE_REGULATION_OF_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_IN_RESPONSE_TO_DNA_DAMAGE, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_NEGATIVE_REGULATION_OF_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_APOPTOTIC_SIGNALING_PATHWAY, MOLENAAR_TARGETS_OF_CCND1_AND_CDK4_DN, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_IN_RESPONSE_TO_DNA_DAMAGE, GOBP_DNA_DAMAGE_RESPONSE, GOBP_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_REGULATION_OF_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_IN_RESPONSE_TO_DNA_DAMAGE, GOBP_NEGATIVE_REGULATION_OF_APOPTOTIC_SIGNALING_PATHWAY

GO Biological Process (5): apoptotic process (GO:0006915), regulation of cell cycle (GO:0051726), regulation of DNA stability (GO:0097752), negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage (GO:1902230), negative regulation of apoptotic process (GO:0043066)

GO Molecular Function (0):

GO Cellular Component (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell cycle	1
regulation of cellular process	1
regulation of biological quality	1
intrinsic apoptotic signaling pathway in response to DNA damage	1
regulation of intrinsic apoptotic signaling pathway in response to DNA damage	1
negative regulation of intrinsic apoptotic signaling pathway	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

908 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DDIAS	PSRC1	Q6PGN9	511
DDIAS	TMEM14A	Q9Y6G1	474
DDIAS	ANAPC2	Q9UJX6	431
DDIAS	MEF2B	Q02080	426
DDIAS	GGH	Q92820	421
DDIAS	PHLDA3	Q9Y5J5	405
DDIAS	RPS3A	P33443	401
DDIAS	BCAP31	P51572	398
DDIAS	MAGEA4	P43358	394
DDIAS	PANK1	Q8TE04	391
DDIAS	DKK4	Q9UBT3	380
DDIAS	AKR7A2	O43488	370
DDIAS	PRR33	A8MZF0	367
DDIAS	TICRR	Q7Z2Z1	363
DDIAS	CPT1C	Q8TCG5	362

IntAct

0 interactions, top by confidence:

BioGRID (23): STUB1 (Two-hybrid), EFEMP1 (Two-hybrid), ECM1 (Two-hybrid), FBLN1 (Two-hybrid), CBY1 (Two-hybrid), MIF4GD (Two-hybrid), ACTN4 (Two-hybrid), ACTN1 (Two-hybrid), MAF1 (Two-hybrid), PLSCR1 (Two-hybrid), ACLY (Two-hybrid), DDIAS (Affinity Capture-Western), STUB1 (Affinity Capture-Western), HSPA4 (Affinity Capture-Western), DDIAS (Affinity Capture-Western)

ESM2 similar proteins: A0A140LI88, A0JM80, A2ALV5, A6QNQ6, A7MBJ2, A8MT70, B1WC58, B2RRF6, D3Z987, D3ZF42, F6SNN2, P56716, P70347, Q283Q6, Q28FY7, Q2M2Z5, Q3U0P1, Q3UXL4, Q3V089, Q499R0, Q5DTT3, Q5HZI1, Q5SVT3, Q5T1N1, Q5W0Q7, Q6AHZ1, Q6NZG4, Q6P0N0, Q6PJP8, Q7TSY8, Q7ZZH7, Q80WQ8, Q80YR6, Q86YC2, Q8CDM4, Q8IXT1, Q8MJ03, Q8MJ04, Q8MJ05, Q8N7Z5

Diamond homologs: Q6NZG4, Q8IXT1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
STUB1	“down-regulates quantity by destabilization”	DDIAS	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	114
Likely benign	15
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

807 predictions. Top by Δscore:

Variant	Effect	Δscore
11:82930150:A:AG	acceptor_gain	1.0000
11:82931726:TCACA:T	acceptor_loss	1.0000
11:82931728:ACAG:A	acceptor_loss	1.0000
11:82931729:C:G	acceptor_gain	1.0000
11:82931730:A:AG	acceptor_gain	1.0000
11:82931730:A:AT	acceptor_loss	1.0000
11:82931731:G:GA	acceptor_gain	1.0000
11:82931731:GA:G	acceptor_gain	1.0000
11:82931731:GAA:G	acceptor_gain	1.0000
11:82931731:GAAT:G	acceptor_gain	1.0000
11:82931731:GAATT:G	acceptor_gain	1.0000
11:82900229:CCTTA:C	donor_loss	0.9900
11:82900230:CTTA:C	donor_loss	0.9900
11:82900231:TTA:T	donor_loss	0.9900
11:82900232:TA:T	donor_loss	0.9900
11:82900233:ACC:A	donor_loss	0.9900
11:82900234:CCTT:C	donor_gain	0.9900
11:82901820:CAGG:C	donor_loss	0.9900
11:82901822:GG:G	donor_loss	0.9900
11:82914863:GTCT:G	donor_gain	0.9900
11:82930151:A:G	acceptor_gain	0.9900
11:82930155:A:G	acceptor_gain	0.9900
11:82931728:A:AG	acceptor_gain	0.9900
11:82914721:A:AG	acceptor_gain	0.9800
11:82914722:G:GG	acceptor_gain	0.9800
11:82928768:C:G	acceptor_gain	0.9800
11:82901835:AAGGG:A	donor_gain	0.9700
11:82926213:C:CG	donor_gain	0.9700
11:82928771:TTCTA:T	acceptor_loss	0.9700
11:82928772:TCTA:T	acceptor_loss	0.9700

AlphaMissense

6628 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:82928839:T:C	L59P	0.982
11:82928784:T:C	C41R	0.980
11:82914820:T:C	C28R	0.977
11:82928886:T:C	F75L	0.977
11:82928888:T:A	F75L	0.977
11:82928888:T:G	F75L	0.977
11:82930227:G:C	A116P	0.976
11:82928832:T:G	Y57D	0.974
11:82914811:T:C	C25R	0.968
11:82928932:T:C	L90S	0.966
11:82914820:T:A	C28S	0.965
11:82914821:G:C	C28S	0.965
11:82928786:T:G	C41W	0.964
11:82928839:T:A	L59H	0.962
11:82930243:T:C	F121S	0.960
11:82914822:C:G	C28W	0.959
11:82930231:T:A	V117D	0.959
11:82928833:A:C	Y57S	0.958
11:82928839:T:G	L59R	0.958
11:82931823:C:A	A162D	0.958
11:82928784:T:A	C41S	0.956
11:82928785:G:C	C41S	0.956
11:82928910:T:C	F83L	0.956
11:82928912:T:A	F83L	0.956
11:82928912:T:G	F83L	0.956
11:82914767:C:A	A10D	0.955
11:82928923:C:A	A87D	0.955
11:82914813:T:G	C25W	0.952
11:82928884:T:A	V74E	0.952
11:82931868:T:A	V177D	0.952

dbSNP variants (sampled 300 via entrez): RS1000024943 (11:82907612 G>A,T), RS1000311161 (11:82921835 T>C,G), RS1000357582 (11:82913336 A>G), RS1000386511 (11:82921576 T>C,G), RS1000468462 (11:82906182 G>A), RS1000485410 (11:82928488 C>T), RS1000813442 (11:82913538 C>A), RS1000901965 (11:82907991 C>A,T), RS1000969788 (11:82901481 C>A), RS1001093729 (11:82916921 A>T), RS1001186002 (11:82912946 G>C), RS1001317121 (11:82901191 C>T), RS1001487232 (11:82925857 G>A), RS1001513607 (11:82926179 G>A,C), RS1001604207 (11:82927681 A>C)

Disease associations

OMIM: gene MIM:618045 | 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
GCST001762_206	Obesity-related traits	6.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004730	hormone measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	3
Aflatoxin B1	affects expression, decreases methylation, increases expression	3
bisphenol A	decreases expression, decreases methylation	2
sodium arsenite	decreases expression, increases expression	2
Air Pollutants	increases abundance, increases expression, decreases expression, affects cotreatment	2
Estradiol	increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression, decreases expression	2
afuresertib	decreases expression	1
dicrotophos	decreases expression	1
beauvericin	decreases expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
sulforaphane	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cypermethrin	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, increases expression	1
incobotulinumtoxinA	decreases expression	1
Dasatinib	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Leflunomide	decreases expression	1
Acetaminophen	increases expression	1
Acrolein	affects cotreatment, increases expression, increases abundance	1
Atrazine	decreases expression	1
Calcitriol	affects cotreatment, decreases expression	1
Cisplatin	decreases expression	1
Coumestrol	affects cotreatment, increases expression	1
Diazinon	increases methylation	1
Mustard Gas	decreases expression	1

Clinical trials (associated diseases)

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