DAP

Summary

DAP (death associated protein, HGNC:2672) is a protein-coding gene on chromosome 5p15.2, encoding Death-associated protein 1 (P51397). Ribosome-binding protein involved in ribosome hibernation, a process during which ribosomes are stabilized in an inactive state and preserved from proteasomal degradation.

This gene encodes a basic, proline-rich, 15-kD protein. The protein acts as a positive mediator of programmed cell death that is induced by interferon-gamma. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.

Source: NCBI Gene 1611 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 22 total
• MANE Select transcript: NM_004394

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2672
Approved symbol	DAP
Name	death associated protein
Location	5p15.2
Locus type	gene with protein product
Status	Approved
Aliases	DAP1
Ensembl gene	ENSG00000112977
Ensembl biotype	protein_coding
OMIM	600954
Entrez	1611

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 3 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000230895, ENST00000432074, ENST00000508253, ENST00000508646, ENST00000510546, ENST00000514882, ENST00000857620

RefSeq mRNA: 2 — MANE Select: NM_004394 NM_001291963, NM_004394

CCDS: CCDS3880, CCDS77997

Canonical transcript exons

ENST00000230895 — 4 exons

Exon	Start	End
ENSE00001641393	10683529	10683571
ENSE00001675313	10679230	10681169
ENSE00001806205	10761014	10761234
ENSE00003682156	10748175	10748271

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 98.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 131.3630 / max 896.4290, expressed in 1828 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
60909	131.3630	1828

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	98.83	gold quality
stromal cell of endometrium	CL:0002255	98.27	gold quality
islet of Langerhans	UBERON:0000006	98.06	gold quality
pancreas	UBERON:0001264	97.82	gold quality
gall bladder	UBERON:0002110	97.52	gold quality
right coronary artery	UBERON:0001625	97.50	gold quality
ascending aorta	UBERON:0001496	97.43	gold quality
thoracic aorta	UBERON:0001515	97.43	gold quality
left adrenal gland	UBERON:0001234	97.25	gold quality
right adrenal gland cortex	UBERON:0035827	97.25	gold quality
left adrenal gland cortex	UBERON:0035825	97.21	gold quality
periodontal ligament	UBERON:0008266	97.17	gold quality
metanephros cortex	UBERON:0010533	97.14	gold quality
right adrenal gland	UBERON:0001233	97.12	gold quality
right lobe of liver	UBERON:0001114	97.10	gold quality
aorta	UBERON:0000947	97.02	gold quality
descending thoracic aorta	UBERON:0002345	97.00	gold quality
body of stomach	UBERON:0001161	96.99	gold quality
popliteal artery	UBERON:0002250	96.78	gold quality
tibial artery	UBERON:0007610	96.78	gold quality
parotid gland	UBERON:0001831	96.73	gold quality
adrenal cortex	UBERON:0001235	96.69	gold quality
right lobe of thyroid gland	UBERON:0001119	96.67	gold quality
left coronary artery	UBERON:0001626	96.66	gold quality
saliva-secreting gland	UBERON:0001044	96.62	gold quality
artery	UBERON:0001637	96.62	gold quality
endometrium epithelium	UBERON:0004811	96.60	gold quality
left lobe of thyroid gland	UBERON:0001120	96.57	gold quality
adenohypophysis	UBERON:0002196	96.53	gold quality
minor salivary gland	UBERON:0001830	96.43	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

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

miRNA regulators (miRDB)

62 targeting DAP, 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-6748-5P	100.00	65.81	1057
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-8076	99.78	68.52	1170
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-4527	99.66	67.43	714
HSA-MIR-6503-5P	99.62	66.96	597
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-5004-3P	99.54	68.27	1371
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-8054	99.48	70.81	2084
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-532-3P	99.34	65.76	1195

Literature-anchored findings (GeneRIF, showing 6)

• Mapping of the phosphorylation sites and analysis of phosphorylation mutants indicated that DAP1 is functionally silenced in growing cells through mTOR-dependent phosphorylations on Ser3 and Ser51 (PMID:20537536)
• This study demonstrates an inverse association between DAP1 mRNA levels and tumour stage and clinical outcome in breast cancer (PMID:22798505)
• DAP1 was found to be correlated with disease progression and long-term survival of the colorectal patients. DAP1 is also a pivotal regulator of the growth and apoptosis and cellular response to chemotherapy agents. (PMID:24270644)
• DAP1 may have an important role in cell adhesion, migration and growth in the context of breast cancer and has significant associations with the apoptosis pathway. (PMID:25530065)
• Backbone and nearly complete side-chain chemical shift assignments of the human death-associated protein 1 (DAP1). (PMID:33263927)
• Expression of Death Associated Proteins DAP1 and DAP3 in Human Pancreatic Cancer. (PMID:33952460)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	dap	ENSDARG00000000069
mus_musculus	Dap	ENSMUSG00000039168
rattus_norvegicus	Dap	ENSRNOG00000010747
drosophila_melanogaster	CG12384	FBGN0033624
caenorhabditis_elegans		WBGENE00010019
caenorhabditis_elegans	T28F4.5	WBGENE00012140

Paralogs (1): DAPL1 (ENSG00000163331)

Protein

Protein identifiers

Death-associated protein 1 — P51397 (reviewed: P51397)

All UniProt accessions (2): B4DQ75, P51397

UniProt curated annotations — full annotation on UniProt →

Function. Ribosome-binding protein involved in ribosome hibernation, a process during which ribosomes are stabilized in an inactive state and preserved from proteasomal degradation. Acts via its association with eiF5a (EIF5A and EIF5A2) at the polypeptide exit tunnel of the ribosome, preventing mRNA translation. Involved in ribosome hibernation in the mature oocyte by preventing mRNA translation, leading to ribosome inactivation. Ribosomes, which are produced in large quantities during oogenesis, are stored and translationally repressed in the oocyte and early embryo. Also acts as a negative regulator of autophagy. Involved in mediating interferon-gamma-induced cell death.

Subunit / interactions. Associates with ribosomes; inhibiting translation. Interacts with eiF5a (EIF5A and EIF5A2); inhibiting translation.

Post-translational modifications. Phosphorylated. Phosphorylation by MTOR inhibits the suppressive activity of DAP toward autophagy.

Similarity. Belongs to the DAP-DAPL1 family.

RefSeq proteins (2): NP_001278892, NP_004385* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR024130	DAP1/DAPL1	Family

Pfam: PF15228

UniProt features (11 total): modified residue 6, compositionally biased region 2, initiator methionine 1, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51397-F1	68.92	0.00

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 (6): 91, 2, 3, 29, 49, 51

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 0 (showing top):

GO Biological Process (6): autophagy (GO:0006914), apoptotic process (GO:0006915), negative regulation of autophagy (GO:0010507), apoptotic signaling pathway (GO:0097190), ribosome hibernation (GO:0141014), regulation of translation (GO:0006417)

GO Molecular Function (1): ribosome binding (GO:0043022)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
autophagy	1
negative regulation of catabolic process	1
regulation of autophagy	1
apoptotic process	1
signal transduction	1
negative regulation of translation	1
translation	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
ribonucleoprotein complex binding	1

Protein interactions and networks

STRING

508 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DAP	DAPK1	P53355	870
DAP	DAXX	Q9UER7	608
DAP	ATRX	P46100	588
DAP	STK17B	O94768	581
DAP	DAPK3	O43293	573
DAP	STK17A	Q9UEE5	572
DAP	CALM1	P02593	544
DAP	CALML6	Q8TD86	542
DAP	CALML4	Q96GE6	542
DAP	CALML3	P27482	541
DAP	CALML5	Q9NZT1	541
DAP	DAPK2	Q9UIK4	480
DAP	AATF	Q9NY61	471
DAP	IFNG	P01579	448
DAP	LHX2	P50458	448

IntAct

10 interactions, top by confidence:

A	B	Type	Score
PIK3CA	PIK3R2	psi-mi:“MI:0914”(association)	0.900
	DAP	psi-mi:“MI:0407”(direct interaction)	0.440
DAP	MAN2C1	psi-mi:“MI:0915”(physical association)	0.400
HTRA4	PSMD12	psi-mi:“MI:0914”(association)	0.350
rep	LAD1	psi-mi:“MI:0914”(association)	0.350
RACK1	RPS3A	psi-mi:“MI:0914”(association)	0.350
RBM8A	MCRIP1	psi-mi:“MI:0914”(association)	0.350
SEC61B	RPS3A	psi-mi:“MI:0914”(association)	0.350
DAP	SETDB1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (13): DAP (Affinity Capture-RNA), SETDB1 (Two-hybrid), DAP (Affinity Capture-MS), MAN2C1 (Affinity Capture-MS), DAP (Affinity Capture-MS), DAP (Affinity Capture-MS), DAP (Affinity Capture-MS), DAP (Affinity Capture-MS), DAP (Affinity Capture-MS), DAP (Cross-Linking-MS (XL-MS)), DAP (Cross-Linking-MS (XL-MS)), DAP (Proximity Label-MS), DAP (Proximity Label-MS)

ESM2 similar proteins: A0MD36, A2VEA7, A3KMT2, A3KMU5, O21950, O56774, O74416, P04972, P0C766, P10430, P13636, P18545, P26352, P35940, P40023, P44588, P51397, P53329, P54827, P61248, P63312, P63313, P63314, P68191, P68192, P68193, P90335, Q02651, Q04558, Q0P641, Q0THU0, Q1RBT8, Q28CI6, Q320R9, Q3Z1M3, Q54UN8, Q57Y88, Q5E969, Q5R853, Q69560

Diamond homologs: A0PJW8, A2VEA7, A3KMT2, A3KMU5, P51397, Q28CI6, Q5EAE6, Q91XC8, Q9D757, Q9I9N0, Q9I9N1, Q9QX67

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
MTOR	“down-regulates activity”	DAP	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1710 predictions. Top by Δscore:

Variant	Effect	Δscore
5:10748184:T:A	donor_gain	1.0000
5:10748190:T:A	donor_gain	1.0000
5:10748199:T:TA	donor_gain	1.0000
5:10748270:CA:C	acceptor_gain	1.0000
5:10748272:C:CC	acceptor_gain	1.0000
5:10681166:CACC:C	acceptor_gain	0.9900
5:10681168:CC:C	acceptor_gain	0.9900
5:10681169:CC:C	acceptor_gain	0.9900
5:10681170:C:CC	acceptor_gain	0.9900
5:10681170:CTGT:C	acceptor_loss	0.9900
5:10681171:T:G	acceptor_loss	0.9900
5:10683572:C:CC	acceptor_gain	0.9900
5:10734114:T:TA	donor_gain	0.9900
5:10734186:T:A	donor_gain	0.9900
5:10734195:C:A	donor_gain	0.9900
5:10748123:A:C	donor_gain	0.9900
5:10748170:CCCA:C	donor_loss	0.9900
5:10748171:CCA:C	donor_loss	0.9900
5:10748172:CA:C	donor_loss	0.9900
5:10748173:A:AG	donor_loss	0.9900
5:10748174:C:T	donor_loss	0.9900
5:10748175:C:A	donor_loss	0.9900
5:10748188:ATT:A	donor_gain	0.9900
5:10748190:T:TA	donor_loss	0.9900
5:10748267:TTTCA:T	acceptor_gain	0.9900
5:10748268:TTCA:T	acceptor_gain	0.9900
5:10748269:TCA:T	acceptor_gain	0.9900
5:10748270:CAC:C	acceptor_gain	0.9900
5:10748270:CACT:C	acceptor_loss	0.9900
5:10748271:ACT:A	acceptor_loss	0.9900

AlphaMissense

670 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:10681130:G:C	H79D	1.000
5:10681132:G:T	A78D	1.000
5:10681144:G:T	A74D	1.000
5:10681155:G:C	F70L	1.000
5:10681155:G:T	F70L	1.000
5:10681157:A:G	F70L	1.000
5:10748250:A:C	I26S	1.000
5:10748250:A:T	I26N	1.000
5:10748262:C:T	G22D	1.000
5:10761026:G:C	H15D	1.000
5:10761028:C:T	G14E	1.000
5:10681064:G:T	R101S	0.999
5:10681066:G:T	P100Q	0.999
5:10681067:G:A	P100S	0.999
5:10681122:C:A	K81N	0.999
5:10681122:C:G	K81N	0.999
5:10681124:T:C	K81E	0.999
5:10681128:G:C	H79Q	0.999
5:10681128:G:T	H79Q	0.999
5:10681141:G:T	A75E	0.999
5:10681156:A:C	F70C	0.999
5:10681156:A:G	F70S	0.999
5:10681160:C:G	D69H	0.999
5:10683542:C:T	G61E	0.999
5:10683543:C:A	G61W	0.999
5:10683548:A:T	I59N	0.999
5:10748250:A:G	I26T	0.999
5:10748253:C:G	R25P	0.999
5:10748253:C:T	R25Q	0.999
5:10748254:G:C	R25G	0.999

dbSNP variants (sampled 300 via entrez): RS1000058205 (5:10698154 G>A), RS1000065010 (5:10694027 T>G), RS1000122864 (5:10731880 C>G), RS1000156719 (5:10750024 G>C), RS1000188790 (5:10706310 T>C), RS1000195103 (5:10733171 T>A,C), RS1000197223 (5:10686138 G>A,C), RS1000201586 (5:10686424 A>G), RS1000259585 (5:10746739 A>G), RS1000274477 (5:10734626 G>A), RS1000352164 (5:10680769 G>T), RS1000352579 (5:10725294 C>A,T), RS1000359432 (5:10700870 C>T), RS1000362807 (5:10689297 CTG>C,CTGTG), RS1000394757 (5:10740769 T>C)

Disease associations

OMIM: gene MIM:600954 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST000964_40	Ulcerative colitis	6.000000e-12
GCST001725_80	Inflammatory bowel disease	1.000000e-08
GCST002118_6	Metabolite levels (Pyroglutamine)	5.000000e-06
GCST003854_52	Gut microbiota (functional units)	4.000000e-06
GCST004131_129	Inflammatory bowel disease	5.000000e-06
GCST004132_77	Crohn’s disease	4.000000e-07
GCST004212_16	Height	3.000000e-08
GCST004624_81	Sum eosinophil basophil counts	4.000000e-09
GCST005537_23	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	6.000000e-09
GCST007096_82	Pulse pressure	1.000000e-07
GCST007099_70	Systolic blood pressure	3.000000e-08
GCST009391_877	Metabolite levels	3.000000e-06
GCST011836_1	Cervical high-risk human papilloma virus infection (persistent)	7.000000e-08
GCST90002380_151	Basophil percentage of white cells	2.000000e-10
GCST90002389_201	Lymphocyte percentage of white cells	2.000000e-13

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0005408	pyroglutamine measurement
EFO:0007874	gut microbiome measurement
EFO:0004842	eosinophil count
EFO:0005090	basophil count
EFO:0005763	pulse pressure measurement
EFO:0006335	systolic blood pressure
EFO:0010403	triacylglycerol 48:0 measurement
EFO:0007992	basophil percentage of leukocytes
EFO:0007993	lymphocyte percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	2
Tunicamycin	increases expression	2
Thapsigargin	increases expression, decreases expression, increases reaction	2
FR900359	decreases phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
cobaltous chloride	decreases expression	1
potassium chromate(VI)	increases expression	1
coumarin	decreases phosphorylation	1
hydroquinone	decreases expression	1
caffeic acid	decreases expression, increases reaction	1
4-methoxycinnamate methyl ester	increases reaction, decreases expression	1
Rosiglitazone	increases expression	1
Acetaminophen	affects response to substance	1
Aspirin	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Capsaicin	increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Drugs, Chinese Herbal	decreases expression, increases reaction	1
Estradiol	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Menthol	decreases expression	1
Phenobarbital	affects expression	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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