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
• GTEx eGene: eQTL in 46 tissues, sQTL in 30 (q < 0.05)
• Constraint (gnomAD): pLI 0.01 (LoF-tolerant), LOEUF 1.29 (unconstrained)
• 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: 11 — 5 protein_coding, 3 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000230895

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 4, TSL 4: 1

ENST00000230895, ENST00000432074, ENST00000508253, ENST00000508646, ENST00000510546, ENST00000514882, ENST00000857620, ENST00000994732, ENST00001119287, ENST00001119288, ENST00001132598

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.

Highest expression (Bgee): body of pancreas, stromal cell of endometrium, islet of Langerhans, pancreas, gall bladder.

Genetic regulation across tissues (GTEx eQTL / sQTL)

DAP is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 46 tissues and its splicing (sQTL) in 30 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 76 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Adipose Subcutaneous	eqtl	1.9e-47	-0.45	5:10675024:G:A
Artery Tibial	eqtl	1.4e-36	-0.34	5:10675380:C:T
Nerve Tibial	eqtl	3.7e-35	-0.38	5:10676097:A:C
Cells Cultured fibroblasts	eqtl	3.2e-33	+0.60	5:10680885:G:A
Esophagus Mucosa	eqtl	1.9e-30	-0.41	5:10675380:C:T
Whole Blood	eqtl	5.7e-30	-0.31	5:10675380:C:T
Pancreas	eqtl	5.1e-28	+1.03	5:10715759:T:C
Breast Mammary Tissue	eqtl	7.8e-27	-0.44	5:10676097:A:C
Esophagus Muscularis	eqtl	9.8e-27	-0.39	5:10675024:G:A
Thyroid	eqtl	2.6e-26	-0.24	5:10680435:T:C
Artery Aorta	eqtl	2.6e-24	-0.34	5:10675380:C:T
Lung	eqtl	1.5e-23	+0.60	5:10680885:G:A
Skin Sun Exposed Lower leg	eqtl	4.7e-23	-0.29	5:10675380:C:T
Artery Tibial	sqtl	6.5e-23	+0.65	5:10741081:T:C
Muscle Skeletal	eqtl	1.4e-21	-0.28	5:10681361:GGGCCCACCAGCGCCCCT:G
Cells EBV-transformed lymphocytes	eqtl	2.5e-20	-0.50	5:10676097:A:C
Adipose Visceral Omentum	eqtl	3.8e-20	-0.35	5:10675024:G:A
Skin Not Sun Exposed Suprapubic	eqtl	6.0e-20	-0.31	5:10675380:C:T
Heart Atrial Appendage	eqtl	1.4e-19	+0.50	5:10680885:G:A
Artery Aorta	sqtl	3.3e-18	+0.71	5:10740310:A:G

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
60909	131.3630	1828

Top tissues by expression

showing 100 of 286 tissues 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
rectum	UBERON:0001052	96.10	gold quality
coronary artery	UBERON:0001621	96.09	gold quality
stomach	UBERON:0000945	96.08	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.08	gold quality
adrenal gland	UBERON:0002369	96.02	gold quality
cortical plate	UBERON:0005343	96.01	gold quality
monocyte	CL:0000576	95.99	gold quality
thyroid gland	UBERON:0002046	95.96	gold quality
upper lobe of left lung	UBERON:0008952	95.77	gold quality
pituitary gland	UBERON:0000007	95.76	gold quality
left ovary	UBERON:0002119	95.74	gold quality
duodenum	UBERON:0002114	95.67	gold quality
mononuclear cell	CL:0000842	95.49	gold quality
leukocyte	CL:0000738	95.42	gold quality
right lung	UBERON:0002167	95.42	gold quality
right ovary	UBERON:0002118	95.39	gold quality
endocervix	UBERON:0000458	95.20	gold quality
left uterine tube	UBERON:0001303	95.11	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.07	gold quality
adult mammalian kidney	UBERON:0000082	95.06	gold quality
body of uterus	UBERON:0009853	95.03	gold quality
ganglionic eminence	UBERON:0004023	94.85	gold quality
small intestine	UBERON:0002108	94.83	gold quality
mucosa of transverse colon	UBERON:0004991	94.80	gold quality
upper lobe of lung	UBERON:0008948	94.69	gold quality
nasal cavity mucosa	UBERON:0001826	94.62	gold quality
right atrium auricular region	UBERON:0006631	94.37	gold quality
smooth muscle tissue	UBERON:0001135	94.35	gold quality
liver	UBERON:0002107	94.30	gold quality
transverse colon	UBERON:0001157	94.18	gold quality
granulocyte	CL:0000094	93.94	gold quality
ectocervix	UBERON:0012249	93.93	gold quality
nerve	UBERON:0001021	93.92	gold quality
fundus of stomach	UBERON:0001160	93.92	gold quality
tibial nerve	UBERON:0001323	93.92	gold quality
mucosa of stomach	UBERON:0001199	93.76	gold quality
mouth mucosa	UBERON:0003729	93.71	gold quality
prostate gland	UBERON:0002367	93.48	gold quality
omental fat pad	UBERON:0010414	93.45	gold quality
peritoneum	UBERON:0002358	93.44	gold quality
colonic epithelium	UBERON:0000397	93.38	gold quality
nasal cavity epithelium	UBERON:0005384	93.38	gold quality
trachea	UBERON:0003126	93.33	gold quality
skin of leg	UBERON:0001511	93.21	gold quality
cardiac atrium	UBERON:0002081	93.10	gold quality
ventricular zone	UBERON:0003053	93.09	gold quality
adipose tissue of abdominal region	UBERON:0007808	92.87	gold quality
urinary bladder	UBERON:0001255	92.85	gold quality
ileal mucosa	UBERON:0000331	92.78	gold quality
subcutaneous adipose tissue	UBERON:0002190	92.72	gold quality
ovary	UBERON:0000992	92.65	gold quality
intestine	UBERON:0000160	92.62	gold quality
skin of abdomen	UBERON:0001416	92.51	gold quality
apex of heart	UBERON:0002098	92.46	gold quality
synovial joint	UBERON:0002217	92.41	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	92.39	gold quality
vermiform appendix	UBERON:0001154	92.27	gold quality
kidney	UBERON:0002113	92.26	gold quality
lymph node	UBERON:0000029	92.14	gold quality
colon	UBERON:0001155	92.10	gold quality
spleen	UBERON:0002106	92.06	gold quality
large intestine	UBERON:0000059	92.05	gold quality
renal medulla	UBERON:0000362	92.04	gold quality
tibia	UBERON:0000979	91.93	gold quality
caecum	UBERON:0001153	91.87	gold quality
pylorus	UBERON:0001166	91.71	gold quality
myometrium	UBERON:0001296	91.60	gold quality
lower esophagus	UBERON:0013473	91.54	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.54	gold quality
muscle layer of sigmoid colon	UBERON:0035805	91.48	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Pancreas	tissue	211.7	medium
Choroid plexus	tissue	150.4
Salivary gland	tissue	122.0	medium
Liver	tissue	105.7	medium
Duodenum	tissue	88.4	medium
Stomach 1	tissue	87.1	medium
Thyroid gland	tissue	87.0	medium
Seminal vesicle	tissue	86.9	low
Urinary bladder	tissue	82.2	low
Small intestine	tissue	82.0	medium
Kidney	tissue	81.9	medium
Pituitary gland	tissue	79.3
Gallbladder	tissue	78.1	medium
Parathyroid gland	tissue	77.9	medium
Ovary	tissue	73.2	not detected
Cervix	tissue	70.5	not detected
Spinal cord	tissue	65.4
Rectum	tissue	64.9	medium
Epididymis	tissue	64.8	high
Breast	tissue	64.6	low
Colon	tissue	61.7	medium
Prostate	tissue	61.7	medium
Placenta	tissue	60.2	medium
Adrenal gland	tissue	59.5	high
Smooth muscle	tissue	59.4	not detected
Fallopian tube	tissue	59.4	not detected
Heart muscle	tissue	50.2	low
Vagina	tissue	48.1	not detected
Lung	tissue	47.6	high
Tonsil	tissue	47.6	low
Endometrium 1	tissue	46.0	medium
Appendix	tissue	44.4	low
Lymph node	tissue	42.7	not detected
Spleen	tissue	42.3	not detected
Bone marrow	tissue	42.0	medium
Thymus	tissue	38.4
Adipose tissue	tissue	38.1	low
Substantia nigra	tissue	37.9
Medulla oblongata	tissue	37.3
Esophagus	tissue	36.4	not detected
Superior colliculi	tissue	35.5
Thalamus	tissue	34.6
Midbrain	tissue	31.3
Hypothalamus	tissue	31.3
Skin 1	tissue	31.2	low
Pons	tissue	31.1
Hippocampus	tissue	30.3	low
Periaqueductal gray	tissue	27.8
Nucleus accumbens	tissue	24.2
Testis	tissue	23.2	high
Corpus callosum	tissue	22.3
Hippocampal formation	tissue	21.2
Septum	tissue	21.2
Putamen	tissue	20.8
Basal ganglia	tissue	19.4	medium
Cerebral cortex	tissue	19.3	low
Motor cortex	tissue	19.3
Locus coeruleus	tissue	19.0
Ventral forebrain	tissue	18.8
Amygdala	tissue	18.1

Brain sub-regions (HPA Brain Atlas): detected in 389; highest nTPM — Blood vessel (120.1), Dorsal spinal cord (65.4), Ventral spinal cord (59.7), Area postrema (43.3), Periaquaductal grey, anterior (37.3).

Regulation

Is transcription factor: no

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

miRNA regulators (miRDB)

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

showing 30 of 62 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 0.00622, LOEUF 1.29, missense Z 0.547 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000230895 — one region, missense o/e 0.80.

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1918190) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 4 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal cornea morphology	1
increased circulating free fatty acids level	1
increased heart weight	1
increased bone mineral content	1

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
Bos taurus	Q5EAE6	96.1%	Diamond
Xenopus laevis	A3KMT2	94.7%	Diamond
Xenopus tropicalis	Q28CI6	94.7%	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
DAP-DT	ncRNA	105374652
CTNND2-AS1	ncRNA	105374654
CTNND2	protein-coding	1501
CTD-2154B17.1	ncRNA	102723441
ANKRD33B	protein-coding	651746
LINC02212	ncRNA	101929412
LINC02213	ncRNA	389273

Protein

Protein identifiers

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

All UniProt accessions (2): P51397, B4DQ75

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

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): mitochondria; vesicles; nucleoplasm

Antibody reliability (HPA): IH uncertain · 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 (6)

Type	Positions
Phosphoserine	91, 3, 49, 51
N-acetylserine	2
N6-acetyllysine	29

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: 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), cytosolic ribosome hibernation (GO:0141014), regulation of translation (GO:0006417)

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

GO top-level categories

16 GO namespaces:

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 cytoplasmic translation	1
translation	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
ribonucleoprotein complex binding	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 7 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
apoptotic process	BP	genetic interaction
apoptotic signaling pathway	BP	mutant phenotype
negative regulation of autophagy	BP	mutant phenotype

Protein interactions and networks

STRING

showing 15 of 400 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DAP	DAPK1	P53355	859
DAP	DAXX	Q9UER7	573
DAP	DAPK3	O43293	539
DAP	STK17B	O94768	536
DAP	STK17A	Q9UEE5	494
DAP	DAPK2	Q9UIK4	441
DAP	IFNG	P01579	437
DAP	DAP3	P51398	405
DAP	CASP8	Q14790	381
DAP	FADD	Q13158	380
DAP	ATRX	P46100	373
DAP	DUSP18	Q8NEJ0	370
DAP	EIF2B4	Q9UI10	360
DAP	HIRA	P54198	359
DAP	TRIAP1	O43715	358

IntAct

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

2 partners by confidence:

Partner	Interaction type	MIscore	Records
MAN2C1	physical association	0.400	1
SETDB1	physical association	0.000	1

BioGRID (14 interactions; top human partners by supporting records): CLIC1 (Affinity Capture-MS), GNB2L1 (Affinity Capture-MS), HNRNPL (Affinity Capture-RNA), HTRA4 (Affinity Capture-MS), MAN2C1 (Affinity Capture-MS), PWP1 (Proximity Label-MS), RBM8A (Affinity Capture-MS), RPL31 (Cross-Linking-MS (XL-MS)), SEC61B (Affinity Capture-MS), SETDB1 (Two-hybrid), WDR26 (Proximity Label-MS), ZRANB1 (Affinity Capture-MS)

SIGNOR signaling

showing 1 of 2 signaling interactions:

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

Disease & clinical

Genetic variants

Variant evidence for DAP: 22 ClinVar records (0 pathogenic / likely pathogenic); 15 GWAS associations.

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

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 31 predictions of 931):

Position(s)	Effect	Δscore	Sites
5:10748184	donor_gain	1.0000
5:10748190	donor_gain	1.0000
5:10681170–10681171	acceptor_loss	0.9900	6
5:10734186	donor_gain	0.9900
5:10734195	donor_gain	0.9900
5:10748123	donor_gain	0.9900
5:10748173–10748175	donor_loss	0.9900	9
5:10748272–10748273	acceptor_loss	0.9900	6
5:10761012–10761013	donor_loss	0.9900	4
5:10761048	donor_gain	0.9900

AlphaMissense

320 missense substitutions predicted likely pathogenic (of 670 scored), across 61 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
M24	9	0.934	0.999
H79	8	0.996	1.000
D69	8	0.994	0.999
H15	8	0.988	1.000
F70	8	0.976	1.000
H30	8	0.851	0.985
Q99	7	0.984	0.998
D67	7	0.962	0.993
I26	7	0.955	1.000
K81	7	0.949	0.999
I97	7	0.885	0.996
Q76	7	0.825	0.996
W47	7	0.808	0.943
P100	6	0.997	0.999
K20	6	0.994	0.999
G61	6	0.994	0.999
G22	6	0.991	1.000
G66	6	0.987	0.998
A18	6	0.983	0.999
K102	6	0.983	0.997

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

5 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	1.63e-06
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	2.51e-06
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	2.68e-05
Lung Adenocarcinoma (validation)	unfavorable	0.000226
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.000284

Disease associations

OMIM: gene MIM:600954 | disease phenotypes:

GWAS associations

15 associations:

Study	Trait	p-value
GCST90002389_46	Lymphocyte percentage of white cells	2e-13
GCST000964_14	Ulcerative colitis	6e-12
GCST90002380_37	Basophil percentage of white cells	2e-10
GCST004624_81	Sum eosinophil basophil counts	4e-9
GCST005537_119	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	6e-9
GCST001725_80	Inflammatory bowel disease	1e-8
GCST004212_24	Height	3e-8
GCST007099_180	Systolic blood pressure	3e-8
GCST011836_1	Cervical high-risk human papilloma virus infection (persistent)	7e-8
GCST007096_57	Pulse pressure	1e-7
GCST004132_62	Crohn’s disease	4e-7
GCST009391_977	Metabolite levels	3e-6
GCST003854_31	Gut microbiota (functional units)	4e-6
GCST002118_7	Metabolite levels (Pyroglutamine)	5e-6
GCST004131_129	Inflammatory bowel disease	5e-6

EFO canonical traits (from GWAS)

9 canonical traits:

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 (CPIC guideline: no)

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	decreases expression, increases reaction, increases expression	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	decreases expression, increases reaction	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)

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