DAPP1

Summary

DAPP1 (dual adaptor of phosphotyrosine and 3-phosphoinositides 1, HGNC:16500) is a protein-coding gene on chromosome 4q23, encoding Dual adapter for phosphotyrosine and 3-phosphotyrosine and 3-phosphoinositide (Q9UN19). May act as a B-cell-associated adapter that regulates B-cell antigen receptor (BCR)-signaling downstream of PI3K.

Enables phosphatidylinositol-3,4,5-trisphosphate binding activity and phosphatidylinositol-3,4-bisphosphate binding activity. Predicted to be involved in protein dephosphorylation and signal transduction. Located in plasma membrane.

Source: NCBI Gene 27071 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 38 total
• MANE Select transcript: NM_014395

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16500
Approved symbol	DAPP1
Name	dual adaptor of phosphotyrosine and 3-phosphoinositides 1
Location	4q23
Locus type	gene with protein product
Status	Approved
Aliases	BAM32
Ensembl gene	ENSG00000070190
Ensembl biotype	protein_coding
OMIM	605768
Entrez	27071

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 retained_intron

ENST00000296414, ENST00000507994, ENST00000512369, ENST00000514301, ENST00000851088

RefSeq mRNA: 2 — MANE Select: NM_014395 NM_001306151, NM_014395

CCDS: CCDS47112, CCDS77945

Canonical transcript exons

ENST00000512369 — 9 exons

Exon	Start	End
ENSE00000339472	99853218	99853348
ENSE00000339474	99863770	99863855
ENSE00001331177	99866034	99866121
ENSE00002024935	99868117	99870190
ENSE00002055872	99816827	99817014
ENSE00003458658	99835623	99835745
ENSE00003460014	99861578	99861625
ENSE00003605437	99840289	99840422
ENSE00003605904	99863010	99863072

Expression profiles

Bgee: expression breadth ubiquitous, 237 present calls, max score 97.95.

FANTOM5 (CAGE): breadth broad, TPM avg 18.3470 / max 1242.4526, expressed in 669 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
49022	17.2194	667
49021	0.8651	212
49023	0.2625	102

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
amniotic fluid	UBERON:0000173	97.95	gold quality
epithelium of nasopharynx	UBERON:0001951	97.79	gold quality
nasopharynx	UBERON:0001728	97.78	gold quality
monocyte	CL:0000576	97.29	gold quality
buccal mucosa cell	CL:0002336	97.06	gold quality
mononuclear cell	CL:0000842	97.00	gold quality
leukocyte	CL:0000738	96.69	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.85	gold quality
cervix squamous epithelium	UBERON:0006922	95.55	gold quality
esophagus squamous epithelium	UBERON:0006920	94.95	gold quality
oral cavity	UBERON:0000167	94.39	gold quality
epithelium of bronchus	UBERON:0002031	94.34	gold quality
bronchial epithelial cell	CL:0002328	94.26	gold quality
cervix epithelium	UBERON:0004801	94.19	gold quality
squamous epithelium	UBERON:0006914	94.16	gold quality
bronchus	UBERON:0002185	94.10	gold quality
palpebral conjunctiva	UBERON:0001812	93.95	gold quality
epithelium of esophagus	UBERON:0001976	93.38	gold quality
sperm	CL:0000019	93.02	silver quality
male germ cell	CL:0000015	92.74	silver quality
vermiform appendix	UBERON:0001154	92.70	gold quality
gingival epithelium	UBERON:0001949	92.40	gold quality
lymph node	UBERON:0000029	92.24	gold quality
caecum	UBERON:0001153	92.19	gold quality
periodontal ligament	UBERON:0008266	91.80	silver quality
gingiva	UBERON:0001828	91.77	gold quality
pancreatic ductal cell	CL:0002079	91.11	silver quality
blood	UBERON:0000178	90.35	gold quality
esophagus mucosa	UBERON:0002469	90.35	gold quality
granulocyte	CL:0000094	90.29	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	81.68
E-CURD-46	yes	19.28
E-MTAB-8498	yes	12.13
E-MTAB-9801	yes	8.20
E-MTAB-6678	yes	7.55
E-GEOD-86618	no	500.32
E-MTAB-5061	no	3.70
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

90 targeting DAPP1, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-664B-3P	99.84	71.65	3590

Literature-anchored findings (GeneRIF, showing 3)

• novel phosphorylation-dependent function of Bam32 in regulating Rac1 activation and actin remodeling. (PMID:15247305)
• BAM32 works downstream of Src family protein tyrosine kinases and functions to link B cell antigen receptor signals with antigen-processing pathways in B cells. (PMID:15494510)
• we propose a role for Bam32 in the signaling of MHC class I molecules in professional Ag-presenting DC for the regulation of CD8(+) T cell activation. (PMID:21930970)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	dapp1	ENSDARG00000039535
mus_musculus	Dapp1	ENSMUSG00000028159
rattus_norvegicus	Dapp1	ENSRNOG00000010575

Paralogs (9): NCK2 (ENSG00000071051), GRAP2 (ENSG00000100351), SLA2 (ENSG00000101082), GRAP (ENSG00000154016), SLA (ENSG00000155926), NCK1 (ENSG00000158092), GRB2 (ENSG00000177885), GRAPL (ENSG00000189152), SH2D5 (ENSG00000189410)

Protein

Protein identifiers

Dual adapter for phosphotyrosine and 3-phosphotyrosine and 3-phosphoinositide — Q9UN19 (reviewed: Q9UN19)

Alternative names: B lymphocyte adapter protein Bam32, B-cell adapter molecule of 32 kDa

All UniProt accessions (2): Q9UN19, J3KNB3

UniProt curated annotations — full annotation on UniProt →

Function. May act as a B-cell-associated adapter that regulates B-cell antigen receptor (BCR)-signaling downstream of PI3K.

Subunit / interactions. Interacts with PtdIns(3,4,5)P3 and PLCG2. In vitro, interacts with PtdIns(3,4)P2.

Subcellular location. Cytoplasm. Membrane.

Tissue specificity. Highly expressed in placenta and lung, followed by brain, heart, kidney, liver, pancreas and skeletal muscle. Expressed by B-lymphocytes, but not T-lymphocytes or nonhematopoietic cells.

Post-translational modifications. Phosphorylated on tyrosine residues.

Induction. Upon B-cell activation.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UN19-1	1, hBam1	yes
Q9UN19-2	2, hBam2

RefSeq proteins (2): NP_001293080, NP_055210* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000980	SH2	Domain
IPR001849	PH_domain	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR035843	DAPP1_SH2	Domain
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR051707	PI-Interact_SigTrans_Reg	Family

Pfam: PF00017, PF00169

UniProt features (23 total): strand 8, mutagenesis site 5, domain 2, helix 2, modified residue 2, chain 1, sequence conflict 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
1FAO	X-RAY DIFFRACTION	1.8
1FB8	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UN19-F1	85.43	0.64

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 (2): 139, 141

Mutagenesis-validated functional residues (5):

Position	Phenotype
197	no membrane association.
250	no interaction with 3-phosphoinositides.
61	no change in bcr-induced nfat activation.
173	no interaction with 3-phosphoinositides.
184	no membrane association.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-983695	Antigen activates B Cell Receptor (BCR) leading to generation of second messengers

MSigDB gene sets: 227 (showing top): PID_BCR_5PATHWAY, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, RODRIGUES_NTN1_TARGETS_DN, IRF7_01, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, RUTELLA_RESPONSE_TO_CSF2RB_AND_IL4_UP, WANG_LMO4_TARGETS_DN, SIG_PIP3_SIGNALING_IN_B_LYMPHOCYTES, IRF1_Q6, RUTELLA_RESPONSE_TO_HGF_VS_CSF2RB_AND_IL4_DN, IRF_Q6, PID_PI3KCI_PATHWAY, RYTTCCTG_ETS2_B, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_UP

GO Biological Process (2): protein dephosphorylation (GO:0006470), signal transduction (GO:0007165)

GO Molecular Function (4): phospholipid binding (GO:0005543), phosphatidylinositol-3,4,5-trisphosphate binding (GO:0005547), phosphatidylinositol-3,4-bisphosphate binding (GO:0043325), protein binding (GO:0005515)

GO Cellular Component (4): cytosol (GO:0005829), plasma membrane (GO:0005886), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Signaling by the B Cell Receptor (BCR)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
dephosphorylation	1
protein modification process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
lipid binding	1
anion binding	1
phosphatidylinositol phosphate binding	1
phosphatidylinositol bisphosphate binding	1
binding	1
cytoplasm	1
membrane	1
cell periphery	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1164 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DAPP1	PLCG2	P16885	870
DAPP1	PLEK	P08567	688
DAPP1	PLEK2	Q9NYT0	687
DAPP1	PLCG1	P19174	674
DAPP1	VAV3	Q9UKW4	630
DAPP1	LYN	P07948	597
DAPP1	AKT1	P31749	594
DAPP1	USP8	P40818	578
DAPP1	BTK	Q06187	578
DAPP1	SYK	P43405	576
DAPP1	LCP2	Q13094	559
DAPP1	GRAP2	O75791	541
DAPP1	SKAP2	O75563	523
DAPP1	NFATC1	O95644	523
DAPP1	MAP4K1	Q92918	520

IntAct

50 interactions, top by confidence:

A	B	Type	Score
FXN	DAPP1	psi-mi:“MI:0915”(physical association)	0.720
WDR20	DAPP1	psi-mi:“MI:0915”(physical association)	0.570
DAPP1	WDR20	psi-mi:“MI:0915”(physical association)	0.570
FAIM	DAPP1	psi-mi:“MI:0915”(physical association)	0.560
LITAF	DAPP1	psi-mi:“MI:0915”(physical association)	0.560
HTT	DAPP1	psi-mi:“MI:0915”(physical association)	0.560
DAPP1	APBB3	psi-mi:“MI:0915”(physical association)	0.510
APBB3	DAPP1	psi-mi:“MI:0915”(physical association)	0.510
MYLIP	DAPP1	psi-mi:“MI:0915”(physical association)	0.490
GSTCD	DAPP1	psi-mi:“MI:0915”(physical association)	0.490
TNFAIP1	DAPP1	psi-mi:“MI:0915”(physical association)	0.490
ZNHIT1	DAPP1	psi-mi:“MI:0915”(physical association)	0.490
DAPP1	MYLIP	psi-mi:“MI:0915”(physical association)	0.490
DAPP1	GSTCD	psi-mi:“MI:0915”(physical association)	0.490
DAPP1	TNFAIP1	psi-mi:“MI:0915”(physical association)	0.490

BioGRID (29): GSTCD (Two-hybrid), MYLIP (Two-hybrid), WDR20 (Two-hybrid), TNFAIP1 (Two-hybrid), ZNHIT1 (Two-hybrid), CNDP2 (Two-hybrid), MGARP (Two-hybrid), RBP7 (Two-hybrid), TM4SF19 (Two-hybrid), APBB3 (Two-hybrid), PLAGL2 (Two-hybrid), APBB3 (Affinity Capture-Luminescence), DAPP1 (Affinity Capture-Luminescence), FAIM (Two-hybrid), FXN (Two-hybrid)

ESM2 similar proteins: A1ZAY1, A2AFR3, A6NI72, A7MBL8, A8MVU1, F1LXF1, F1M707, O15034, O75563, O77774, O88382, O95267, P11274, P14598, P15498, P27870, P28028, P54100, Q09014, Q14161, Q16513, Q32LP7, Q3LAC4, Q3UND0, Q3ZBA3, Q5BKC9, Q5RDS2, Q5RDX5, Q66H91, Q69ZK0, Q6PAJ1, Q70Z35, Q80U40, Q86UL8, Q8BWW9, Q8CHT1, Q8N5V2, Q8TCU6, Q920G0, Q99N48

Diamond homologs: A0A8I3NFE2, A0FI79, A0JNB0, A1Y2K1, A6QLK6, B2RZ59, B5KFD7, D3ZGS3, D7PF45, F1RDG9, G5ECJ6, O14306, O14796, O15357, O35324, O60880, O88890, O88900, P00519, P00520, P00521, P00522, P03949, P06239, P06241, P09851, P0CE43, P10447, P17713, P20936, P29350, P29351, P32019, P34370, P39688, P42684, P42685, P42686, P50904, P53356

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
SRC	“up-regulates activity”	DAPP1	phosphorylation
BTK	“up-regulates activity”	DAPP1	phosphorylation
LCK	“up-regulates activity”	DAPP1	phosphorylation
LYN	“up-regulates activity”	DAPP1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1283 predictions. Top by Δscore:

Variant	Effect	Δscore
4:99817013:GG:G	donor_gain	1.0000
4:99817014:GG:G	donor_gain	1.0000
4:99817014:GGT:G	donor_loss	1.0000
4:99817015:G:A	donor_loss	1.0000
4:99817016:T:G	donor_loss	1.0000
4:99835617:TTCTA:T	acceptor_loss	1.0000
4:99835618:TCTA:T	acceptor_loss	1.0000
4:99835619:CTA:C	acceptor_loss	1.0000
4:99835620:TA:T	acceptor_loss	1.0000
4:99835621:AGGT:A	acceptor_gain	1.0000
4:99835622:GGT:G	acceptor_gain	1.0000
4:99835622:GGTG:G	acceptor_gain	1.0000
4:99835746:G:C	donor_loss	1.0000
4:99835747:T:A	donor_loss	1.0000
4:99840287:A:AG	acceptor_gain	1.0000
4:99840288:G:GG	acceptor_gain	1.0000
4:99840419:ACAGG:A	donor_loss	1.0000
4:99840421:AGG:A	donor_loss	1.0000
4:99840424:T:A	donor_loss	1.0000
4:99853349:G:GG	donor_gain	1.0000
4:99861576:AGCT:A	acceptor_gain	1.0000
4:99861577:GCTG:G	acceptor_gain	1.0000
4:99863008:A:AG	acceptor_gain	1.0000
4:99863009:G:GA	acceptor_gain	1.0000
4:99863069:GATG:G	donor_gain	1.0000
4:99863766:TTAGT:T	acceptor_loss	1.0000
4:99863768:A:AG	acceptor_gain	1.0000
4:99863769:G:GA	acceptor_gain	1.0000
4:99863769:GT:G	acceptor_gain	1.0000
4:99863769:GTC:G	acceptor_gain	1.0000

AlphaMissense

1821 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:99861600:T:C	L171P	1.000
4:99861607:A:C	K173N	1.000
4:99861607:A:T	K173N	1.000
4:99863013:T:A	W181R	1.000
4:99863013:T:C	W181R	1.000
4:99863050:T:C	L193P	1.000
4:99866095:T:A	W250R	1.000
4:99866095:T:C	W250R	1.000
4:99835624:T:A	W35R	0.999
4:99835624:T:C	W35R	0.999
4:99835667:T:C	L49P	0.999
4:99835693:T:G	Y58D	0.999
4:99835697:T:C	L59P	0.999
4:99840303:T:A	V80D	0.999
4:99840318:T:A	V85D	0.999
4:99861593:G:C	G169R	0.999
4:99861600:T:A	L171H	0.999
4:99861605:A:G	K173E	0.999
4:99863015:G:C	W181C	0.999
4:99863015:G:T	W181C	0.999
4:99863023:G:C	R184T	0.999
4:99863024:A:C	R184S	0.999
4:99863024:A:T	R184S	0.999
4:99863025:T:A	W185R	0.999
4:99863025:T:C	W185R	0.999
4:99863035:T:C	L188P	0.999
4:99863055:T:C	Y195H	0.999
4:99863798:T:C	L210P	0.999
4:99863806:T:C	C213R	0.999
4:99863808:T:G	C213W	0.999

dbSNP variants (sampled 300 via entrez): RS1000076478 (4:99824383 A>G), RS1000169571 (4:99861702 T>C,G), RS1000178676 (4:99819469 A>C), RS1000255127 (4:99853690 G>GCA), RS1000273184 (4:99855164 C>A,G), RS10002820 (4:99869657 C>T), RS1000305491 (4:99849509 A>G), RS1000325068 (4:99830238 G>T), RS1000388482 (4:99855450 A>T), RS1000414743 (4:99849191 T>C), RS1000429106 (4:99821273 C>T), RS1000435118 (4:99835827 A>G), RS1000549397 (4:99835999 T>C), RS1000602450 (4:99872311 T>A), RS1000614297 (4:99869211 G>A,T)

Disease associations

OMIM: gene MIM:605768 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST011176_6	Stroke	8.000000e-07
GCST90002404_83	Red cell distribution width	4.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009188	Red cell distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, affects expression	3
Zoledronic Acid	increases expression	2
Particulate Matter	increases abundance, increases expression	2
aristolochic acid I	increases expression	1
bisphenol A	affects cotreatment, increases methylation	1
sulforaphane	decreases expression	1
hydroquinone	increases expression	1
CGP 52608	affects binding, increases reaction	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
abrine	increases expression	1
Arsenic Trioxide	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Cisplatin	increases expression	1
Diethylhexyl Phthalate	increases expression	1
Estradiol	increases expression	1
Formaldehyde	increases expression	1
Hydrogen Peroxide	affects expression	1
Nickel	increases expression	1
Plant Oils	increases expression	1
Silicon Dioxide	increases expression	1
Dronabinol	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
Asbestos, Crocidolite	decreases expression	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_F1TZ	HyCyte THP-1 KO-hDAPP1	Cancer cell line	Male

Clinical trials (associated diseases)

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