DAPL1

Summary

DAPL1 (death associated protein like 1, HGNC:21490) is a protein-coding gene on chromosome 2q24.1, encoding Death-associated protein-like 1 (A0PJW8). May play a role in the early stages of epithelial differentiation or in apoptosis.

Predicted to enable ribosome binding activity; translation initiation factor binding activity; and translation repressor activity. Predicted to be involved in apoptotic signaling pathway; negative regulation of CD8-positive, alpha-beta T cell activation; and negative regulation of metabolic process. Predicted to act upstream of or within cell population proliferation and gene expression. Predicted to be located in membrane. Predicted to be active in nucleus.

Source: NCBI Gene 92196 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 32 total
• MANE Select transcript: NM_001017920

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21490
Approved symbol	DAPL1
Name	death associated protein like 1
Location	2q24.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000163331
Ensembl biotype	protein_coding
Entrez	92196

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000309950, ENST00000343761, ENST00000409042, ENST00000621326

RefSeq mRNA: 1 — MANE Select: NM_001017920 NM_001017920

CCDS: CCDS33307

Canonical transcript exons

ENST00000309950 — 4 exons

Exon	Start	End
ENSE00001073400	158804282	158804369
ENSE00001294028	158815705	158815990
ENSE00001600681	158807055	158807115
ENSE00003899587	158795317	158795430

Expression profiles

Bgee: expression breadth ubiquitous, 192 present calls, max score 99.32.

FANTOM5 (CAGE): breadth broad, TPM avg 3.2442 / max 656.2626, expressed in 321 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
23227	3.2442	321

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	99.32	gold quality
skin of abdomen	UBERON:0001416	98.58	gold quality
skin of leg	UBERON:0001511	98.41	gold quality
lower esophagus mucosa	UBERON:0035834	98.40	gold quality
zone of skin	UBERON:0000014	98.25	gold quality
penis	UBERON:0000989	97.91	gold quality
gingiva	UBERON:0001828	97.84	gold quality
gingival epithelium	UBERON:0001949	97.80	gold quality
mammalian vulva	UBERON:0000997	97.75	gold quality
esophagus mucosa	UBERON:0002469	97.10	gold quality
right uterine tube	UBERON:0001302	96.73	gold quality
upper leg skin	UBERON:0004262	96.26	gold quality
corpus epididymis	UBERON:0004359	95.62	gold quality
oral cavity	UBERON:0000167	94.90	gold quality
skin of hip	UBERON:0001554	94.86	gold quality
pharyngeal mucosa	UBERON:0000355	94.80	gold quality
nasal cavity epithelium	UBERON:0005384	92.58	gold quality
nipple	UBERON:0002030	92.32	gold quality
esophagus squamous epithelium	UBERON:0006920	92.19	gold quality
right adrenal gland cortex	UBERON:0035827	89.86	gold quality
cauda epididymis	UBERON:0004360	89.44	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.11	gold quality
oviduct epithelium	UBERON:0004804	88.73	gold quality
left adrenal gland cortex	UBERON:0035825	88.72	gold quality
left adrenal gland	UBERON:0001234	88.53	gold quality
nasal cavity mucosa	UBERON:0001826	88.51	gold quality
pigmented layer of retina	UBERON:0001782	88.29	gold quality
fallopian tube	UBERON:0003889	88.26	gold quality
parotid gland	UBERON:0001831	88.15	gold quality
vagina	UBERON:0000996	88.00	gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-MTAB-11121	yes	1397.00
E-MTAB-10485	yes	1307.95
E-HCAD-5	yes	861.54
E-MTAB-7316	yes	857.20
E-HCAD-1	yes	822.73
E-GEOD-124472	yes	816.38
E-GEOD-114530	yes	723.89
E-CURD-114	yes	545.27
E-HCAD-10	yes	43.10
E-GEOD-137537	yes	40.67
E-MTAB-10596	no	1180.82
E-MTAB-6108	no	1136.83
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

8 targeting DAPL1, 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-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4639-5P	99.81	67.37	1028
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-3944-5P	98.50	67.55	997
HSA-MIR-6851-3P	95.73	65.11	688
HSA-MIR-328-3P	92.82	64.37	521

Literature-anchored findings (GeneRIF, showing 5)

• DAPL1 plays a role in epithelial differentiation and may be involved in apoptotic processes thereby suggesting a possible novel pathway in AMD pathogenesis. (PMID:25680934)
• Authors show that DAPL1 is a novel regulator of RPE cell proliferation that is important for the maintenance of the RPE as a monolayer. The findings suggest that DAPL1 dysregulation may be involved in abnormal RPE-related proliferative diseases and corresponding retinal dysfunctions in humans. (PMID:28334846)
• human retinal pigment epithelium (RPE) cell lines that the pigment cell transcription factor MITF regulates RPE cell proliferation by upregulating DAPL1 expression. (PMID:29171181)
• [Hypomethylation of DAPL1 associated with prognosis of lung cancer patients with EGFR Del19 mutation]. (PMID:34915634)
• Transcriptomics Analysis of Lens from Patients with Posterior Subcapsular Congenital Cataract. (PMID:34946854)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	dap1b	ENSDARG00000086842
danio_rerio		ENSDARG00000109678
mus_musculus	Dapl1	ENSMUSG00000026989
rattus_norvegicus	Dapl1	ENSRNOG00000005743
drosophila_melanogaster	CG12384	FBGN0033624
caenorhabditis_elegans		WBGENE00010019
caenorhabditis_elegans	T28F4.5	WBGENE00012140

Paralogs (1): DAP (ENSG00000112977)

Protein

Protein identifiers

Death-associated protein-like 1 — A0PJW8 (reviewed: A0PJW8)

Alternative names: Early epithelial differentiation-associated protein

All UniProt accessions (5): A0PJW8, B8ZZC6, H0Y3U5, M1E9T5, M1EA23

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in the early stages of epithelial differentiation or in apoptosis.

Tissue specificity. Expressed in hair follicle (at protein level).

RefSeq proteins (1): NP_001017920* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR024130	DAP1/DAPL1	Family

Pfam: PF15228

UniProt features (4 total): sequence variant 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A0PJW8-F1	68.31	0.03

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 173 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_NEGATIVE_REGULATION_OF_CELL_CELL_ADHESION, GOBP_NEGATIVE_REGULATION_OF_TRANSLATION, GOBP_TRANSLATION, GOBP_CELL_CELL_ADHESION, GOBP_NEGATIVE_REGULATION_OF_AUTOPHAGY, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOMF_TRANSLATION_REGULATOR_ACTIVITY, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_APOPTOTIC_SIGNALING_PATHWAY, GOBP_REGULATION_OF_CATABOLIC_PROCESS, chr2q24

GO Biological Process (12): cell population proliferation (GO:0008283), gene expression (GO:0010467), negative regulation of autophagy (GO:0010507), cell differentiation (GO:0030154), apoptotic signaling pathway (GO:0097190), ribosome hibernation (GO:0141014), negative regulation of CD8-positive, alpha-beta T cell activation (GO:2001186), apoptotic process (GO:0006915), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), sensory perception of smell (GO:0007608), detection of chemical stimulus involved in sensory perception of smell (GO:0050911)

GO Molecular Function (6): translation repressor activity (GO:0030371), translation initiation factor binding (GO:0031369), ribosome binding (GO:0043022), G protein-coupled receptor activity (GO:0004930), olfactory receptor activity (GO:0004984), protein binding (GO:0005515)

GO Cellular Component (2): nucleus (GO:0005634), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	2
signal transduction	2
negative regulation of translation	2
transmembrane signaling receptor activity	2
macromolecule biosynthetic process	1
autophagy	1
negative regulation of catabolic process	1
regulation of autophagy	1
cellular developmental process	1
apoptotic process	1
CD8-positive, alpha-beta T cell activation	1
negative regulation of alpha-beta T cell activation	1
regulation of CD8-positive, alpha-beta T cell activation	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor activity	1
sensory perception of chemical stimulus	1
sensory perception of smell	1
detection of chemical stimulus involved in sensory perception	1
translation regulator activity	1
protein binding	1
ribonucleoprotein complex binding	1
G protein-coupled receptor signaling pathway	1
detection of chemical stimulus involved in sensory perception of smell	1
binding	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

937 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DAPL1	DRC12	Q494R4	557
DAPL1	LYPD2	Q6UXB3	391
DAPL1	CFAP263	Q9H0I3	385
DAPL1	LYPD1	Q8N2G4	360
DAPL1	LZTFL1	Q9NQ48	353
DAPL1	CITED1	Q99966	335
DAPL1	ASCL3	Q9NQ33	323
DAPL1	KRT4	P19013	322
DAPL1	LRRN4CL	Q8ND94	318
DAPL1	ENKD1	Q9H0I2	298
DAPL1	LRRC32	Q14392	296
DAPL1	PPIAL4C	A0A0B4J2A2	290
DAPL1	ERMN	Q8TAM6	290
DAPL1	SAPCD2	Q86UD0	289
DAPL1	GRIFIN	A4D1Z8	285

IntAct

21 interactions, top by confidence:

A	B	Type	Score
TSR2	DAPL1	psi-mi:“MI:0915”(physical association)	0.560
DAPL1	FNDC3B	psi-mi:“MI:0915”(physical association)	0.560
DAPL1	ZIC1	psi-mi:“MI:0915”(physical association)	0.560
DAPL1	LSM1	psi-mi:“MI:0915”(physical association)	0.560
DAPL1	TSR2	psi-mi:“MI:0915”(physical association)	0.560
DAPL1	FHL2	psi-mi:“MI:0915”(physical association)	0.560
DAPL1		psi-mi:“MI:0915”(physical association)	0.560
TRIM63	DAPL1	psi-mi:“MI:0915”(physical association)	0.000
TRIM55	DAPL1	psi-mi:“MI:0915”(physical association)	0.000
ZIC1	DAPL1	psi-mi:“MI:0915”(physical association)	0.000
FNDC3B	DAPL1	psi-mi:“MI:0915”(physical association)	0.000
FHL2	DAPL1	psi-mi:“MI:0915”(physical association)	0.000
LSM1	DAPL1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (8): DAPL1 (Two-hybrid), DAPL1 (Two-hybrid), DAPL1 (Two-hybrid), DAPL1 (Two-hybrid), LSM1 (Two-hybrid), DAPL1 (Two-hybrid), DAPL1 (Two-hybrid), DAPL1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GVR7, A0PJW8, A2BYT2, A5FRX9, B8G1X0, C1DKL7, G3UWD5, O42659, O62953, O95567, O98453, P05899, P11690, P11794, P19718, P20920, P27975, P32544, P33482, P39971, P52776, P54446, P69516, P69517, P86209, Q02781, Q0ABH1, Q1X6Y0, Q3AMN4, Q3J8R8, Q3K5Z2, Q3MFB7, Q3ZZM0, Q537H7, Q57P89, Q5I162, Q5PHY6, Q6AY31, Q75003, Q7CQJ0

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	23
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

622 predictions. Top by Δscore:

Variant	Effect	Δscore
2:158804280:A:AG	acceptor_gain	1.0000
2:158804281:G:GG	acceptor_gain	1.0000
2:158804281:GTA:G	acceptor_gain	1.0000
2:158804281:GTAA:G	acceptor_gain	1.0000
2:158804366:CAAGG:C	donor_loss	1.0000
2:158804367:AAG:A	donor_loss	1.0000
2:158804368:AGGTA:A	donor_loss	1.0000
2:158804370:GTAGG:G	donor_loss	1.0000
2:158804371:T:A	donor_loss	1.0000
2:158807053:A:AG	acceptor_gain	1.0000
2:158807054:G:GG	acceptor_gain	1.0000
2:158804273:T:TA	acceptor_gain	0.9900
2:158804277:TGTA:T	acceptor_loss	0.9900
2:158804279:TAGT:T	acceptor_loss	0.9900
2:158804280:A:C	acceptor_loss	0.9900
2:158804281:GT:G	acceptor_gain	0.9900
2:158804281:GTAAA:G	acceptor_gain	0.9900
2:158807054:GT:G	acceptor_gain	0.9900
2:158807054:GTGCC:G	acceptor_gain	0.9800
2:158804270:ATCT:A	acceptor_gain	0.9700
2:158804281:G:T	acceptor_gain	0.9700
2:158804370:G:GG	donor_gain	0.9700
2:158815703:A:AG	acceptor_gain	0.9700
2:158815704:G:GG	acceptor_gain	0.9700
2:158795516:G:GT	donor_gain	0.9600
2:158804277:T:TA	acceptor_gain	0.9600
2:158804279:TAG:T	acceptor_gain	0.9600
2:158807183:A:G	donor_gain	0.9600
2:158795426:TGCAG:T	donor_loss	0.9500
2:158795428:CAGGT:C	donor_loss	0.9500

AlphaMissense

692 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:158815799:T:A	I101N	0.934
2:158804301:A:C	R26S	0.933
2:158804301:A:T	R26S	0.933
2:158815799:T:C	I101T	0.930
2:158815799:T:G	I101S	0.920
2:158804286:A:C	K21N	0.911
2:158804286:A:T	K21N	0.911
2:158815806:G:C	Q103H	0.898
2:158815806:G:T	Q103H	0.898
2:158815807:C:T	P104S	0.893
2:158815808:C:A	P104H	0.875
2:158815811:G:C	R105P	0.860
2:158804310:A:C	K29N	0.856
2:158804310:A:T	K29N	0.856
2:158815807:C:A	P104T	0.853
2:158795428:C:A	A19E	0.827
2:158804300:G:C	R26T	0.822
2:158815815:A:C	K106N	0.821
2:158815815:A:T	K106N	0.821
2:158815749:A:C	K84N	0.820
2:158815749:A:T	K84N	0.820
2:158815816:T:C	C107R	0.819
2:158815808:C:T	P104L	0.817
2:158795418:C:G	H16D	0.815
2:158804291:G:A	G23E	0.807
2:158815808:C:G	P104R	0.791
2:158804309:A:T	K29I	0.769
2:158815818:T:G	C107W	0.764
2:158804299:A:G	R26G	0.759
2:158815717:T:C	F74L	0.758

dbSNP variants (sampled 300 via entrez): RS1000037431 (2:158807805 C>A), RS1000208151 (2:158799056 T>G), RS1000245212 (2:158815943 C>A,T), RS1000284617 (2:158805019 A>G), RS1000326223 (2:158810505 C>G), RS1000582885 (2:158796658 C>T), RS1000638285 (2:158806612 A>G), RS1000664648 (2:158811795 A>C), RS1000683334 (2:158809011 A>G), RS1000769023 (2:158812074 G>A,T), RS1000904661 (2:158806175 A>G,T), RS1000987059 (2:158800352 C>A), RS1001018052 (2:158800109 C>G,T), RS1001168257 (2:158802806 C>G,T), RS1001190739 (2:158803576 T>G)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001762_944	Obesity-related traits	1.000000e-06
GCST002813_13	Alzheimer’s disease in APOE e4+ carriers	4.000000e-06
GCST009360_2	LDL cholesterol levels x long total sleep time interaction (1df test)	8.000000e-07
GCST009366_10	LDL cholesterol levels x long total sleep time interaction (2df test)	6.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, increases expression	4
sodium arsenite	decreases expression, increases expression	2
propionaldehyde	increases expression	1
hydroquinone	decreases expression	1
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline	increases expression	1
monomethylarsonous acid	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Diethylhexyl Phthalate	decreases expression	1
Formaldehyde	decreases expression	1
Nickel	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Sodium Dodecyl Sulfate	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Lactic Acid	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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