NYAP2

Summary

NYAP2 (neuronal tyrosine-phosphorylated phosphoinositide-3-kinase adaptor 2, HGNC:29291) is a protein-coding gene on chromosome 2q36.3, encoding Neuronal tyrosine-phosphorylated phosphoinositide-3-kinase adapter 2 (Q9P242). Activates PI3K and concomitantly recruits the WAVE1 complex to the close vicinity of PI3K and regulates neuronal morphogenesis.

Predicted to be involved in neuron projection morphogenesis and phosphatidylinositol 3-kinase/protein kinase B signal transduction.

Source: NCBI Gene 57624 — RefSeq curated summary.

At a glance

• GWAS associations: 21
• Clinical variants (ClinVar): 102 total
• MANE Select transcript: NM_001371273

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29291
Approved symbol	NYAP2
Name	neuronal tyrosine-phosphorylated phosphoinositide-3-kinase adaptor 2
Location	2q36.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000144460
Ensembl biotype	protein_coding
OMIM	615478
Entrez	57624

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000272907, ENST00000636099, ENST00000695958, ENST00000695959

RefSeq mRNA: 2 — MANE Select: NM_001371273 NM_001371273, NM_020864

CCDS: CCDS46529, CCDS92950

Canonical transcript exons

ENST00000272907 — 8 exons

Exon	Start	End
ENSE00001169913	225626917	225627126
ENSE00001316344	225400561	225401043
ENSE00001506598	225581941	225583035
ENSE00001506606	225513371	225513672
ENSE00001687005	225408864	225409101
ENSE00001740803	225399710	225400255
ENSE00003965620	225651432	225651535
ENSE00003965621	225698317	225703654

Expression profiles

Bgee: expression breadth broad, 78 present calls, max score 78.98.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.9067 / max 230.7087, expressed in 126 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
25675	1.1371	105
25674	0.3985	100
25672	0.3376	88
25673	0.0336	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	78.98	gold quality
colonic epithelium	UBERON:0000397	73.16	gold quality
ganglionic eminence	UBERON:0004023	66.38	gold quality
prefrontal cortex	UBERON:0000451	62.26	gold quality
islet of Langerhans	UBERON:0000006	60.58	gold quality
bone marrow cell	CL:0002092	57.26	gold quality
ventricular zone	UBERON:0003053	54.49	silver quality
descending thoracic aorta	UBERON:0002345	53.15	gold quality
frontal cortex	UBERON:0001870	53.12	gold quality
gastrocnemius	UBERON:0001388	52.23	gold quality
neocortex	UBERON:0001950	52.05	gold quality
muscle of leg	UBERON:0001383	51.81	gold quality
hindlimb stylopod muscle	UBERON:0004252	50.88	gold quality
cerebellar cortex	UBERON:0002129	50.81	gold quality
cerebellum	UBERON:0002037	50.52	gold quality
cerebellar hemisphere	UBERON:0002245	50.46	gold quality
right hemisphere of cerebellum	UBERON:0014890	49.23	silver quality
cerebellar vermis	UBERON:0004720	48.93	gold quality
cerebral cortex	UBERON:0000956	48.84	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	48.56	gold quality
stromal cell of endometrium	CL:0002255	48.11	gold quality
skeletal muscle tissue	UBERON:0001134	47.87	silver quality
anterior cingulate cortex	UBERON:0009835	47.35	gold quality
brain	UBERON:0000955	47.21	gold quality
buccal mucosa cell	CL:0002336	47.16	silver quality
primary visual cortex	UBERON:0002436	47.04	gold quality
nucleus accumbens	UBERON:0001882	46.87	gold quality
skin of hip	UBERON:0001554	46.68	silver quality
forebrain	UBERON:0001890	46.68	gold quality
Brodmann (1909) area 9	UBERON:0013540	46.60	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	8.40
E-ANND-3	yes	4.57
E-GEOD-83139	yes	3.82

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

135 targeting NYAP2, 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-8485	100.00	77.57	4731
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-5688	99.96	73.23	4504
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nyap2a	ENSDARG00000079581
danio_rerio	nyap2b	ENSDARG00000093357
mus_musculus	Nyap2	ENSMUSG00000054976
rattus_norvegicus	Nyap2	ENSRNOG00000023765

Paralogs (1): NYAP1 (ENSG00000166924)

Protein

Protein identifiers

Neuronal tyrosine-phosphorylated phosphoinositide-3-kinase adapter 2 — Q9P242 (reviewed: Q9P242)

All UniProt accessions (3): Q9P242, A0A8Q3SIC2, A0A8V8N5G5

UniProt curated annotations — full annotation on UniProt →

Function. Activates PI3K and concomitantly recruits the WAVE1 complex to the close vicinity of PI3K and regulates neuronal morphogenesis.

Subunit / interactions. Interacts with ACOT9, ARHGAP26 and PIK3R2. Interacts with components of the WAVE1 complex, CYFIP1 and NCKAP1; this interaction mediates PI3K-WAVE1 association and actin cytoskeleton remodeling.

Post-translational modifications. Phosphorylated on tyrosine residues by FYN upon stimulation with CNTN5.

Similarity. Belongs to the NYAP family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9P242-1	1	yes
Q9P242-2	2
Q9P242-3	3

RefSeq proteins (2): NP_001358202, NP_065915 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026722	NYAP1/NYAP2	Family
IPR029353	NYAP_C	Domain
IPR039482	NYAP_N	Domain

Pfam: PF15439, PF15452

UniProt features (27 total): compositionally biased region 11, modified residue 5, splice variant 5, region of interest 3, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P242-F1	55.09	0.08

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 (5): 81, 120, 206, 268, 434

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 0 (showing top):

GO Biological Process (2): phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0043491), neuron projection morphogenesis (GO:0048812)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular signaling cassette	1
neuron projection development	1
plasma membrane bounded cell projection morphogenesis	1
binding	1

Protein interactions and networks

STRING

558 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NYAP2	WASF1	Q92558	534
NYAP2	NYAP1	Q6ZVC0	482
NYAP2	MYO16	Q9Y6X6	428
NYAP2	FAM110D	Q8TAY7	425
NYAP2	PRR7	Q8TB68	407
NYAP2	SLC10A4	Q96EP9	383
NYAP2	SLC44A5	Q8NCS7	363
NYAP2	SPATA6L	Q8N4H0	350
NYAP2	ABT1	Q9ULW3	348
NYAP2	TSPYL6	Q8N831	348
NYAP2	ZNF385D	Q9H6B1	346
NYAP2	ZGLP1	P0C6A0	336
NYAP2	VSTM4	Q8IW00	334
NYAP2	TMIGD3	P0DMS9	329
NYAP2	PTPN4	P29074	324

IntAct

11 interactions, top by confidence:

A	B	Type	Score
MORN4	NYAP2	psi-mi:“MI:0915”(physical association)	0.670
NYAP2	MORN4	psi-mi:“MI:0915”(physical association)	0.670
AGFG1	NYAP2	psi-mi:“MI:0915”(physical association)	0.560
Dlc1	NYAP2	psi-mi:“MI:0915”(physical association)	0.400
PIK3R1	PIK3CD	psi-mi:“MI:0914”(association)	0.350
NYAP2	SEMG1	psi-mi:“MI:0914”(association)	0.350
FYN	NYAP2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (21): NYAP2 (Two-hybrid), MORN4 (Two-hybrid), NYAP2 (Affinity Capture-MS), NYAP2 (Affinity Capture-MS), NCKAP1 (Affinity Capture-Western), CYFIP2 (Affinity Capture-Western), CYFIP1 (Reconstituted Complex), NCKAP1 (Reconstituted Complex), PIK3R1 (Reconstituted Complex), ARHGAP26 (Affinity Capture-Western), ACOT9 (Affinity Capture-Western), WASF1 (Reconstituted Complex), NYAP2 (Affinity Capture-RNA), NYAP2 (Proximity Label-MS), SEMG1 (Affinity Capture-MS)

ESM2 similar proteins: A1X283, A2AAY5, A2AI08, A2VDK6, A6NGB9, D3ZUI5, O62674, O62676, O70305, O75128, P0C7L0, Q03173, Q04584, Q0IIJ3, Q15942, Q3SZL6, Q3TC93, Q3UZA1, Q3ZBT0, Q4KM52, Q5BJU7, Q5NBX1, Q5NVG8, Q5R413, Q5SV85, Q5XHX2, Q62415, Q62523, Q6ZU35, Q80XA6, Q8BH43, Q8BM65, Q8CG79, Q8IZD4, Q8N3V7, Q8NFH8, Q8R5H6, Q8TD55, Q8VHI6, Q8WV28

Diamond homologs: A5PF48, D3ZJP6, E9Q634, F4I507, F4IUG9, F4K0A6, F8VQB6, K7U9N8, O00159, O00160, P05659, P10569, P19524, P19706, P22467, P32492, P34092, P42522, P79114, P91443, Q03479, Q12965, Q1EG27, Q27966, Q28970, Q39160, Q5DU14, Q5ZLA6, Q622K8, Q63355, Q63356, Q6CVE9, Q6PFX7, Q6ZVC0, Q7SDM3, Q875Q8, Q876G9, Q8BM65, Q8K3H5, Q8N1T3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	92
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1507 predictions. Top by Δscore:

Variant	Effect	Δscore
2:225408863:GGCA:G	acceptor_gain	1.0000
2:225409099:GCG:G	donor_gain	1.0000
2:225409102:G:GG	donor_gain	1.0000
2:225583034:GA:G	donor_gain	1.0000
2:225627079:G:GT	donor_gain	1.0000
2:225408859:TGCA:T	acceptor_loss	0.9900
2:225408860:GCAG:G	acceptor_loss	0.9900
2:225408861:CA:C	acceptor_loss	0.9900
2:225408862:A:AG	acceptor_gain	0.9900
2:225408862:AGGC:A	acceptor_loss	0.9900
2:225408863:G:GG	acceptor_gain	0.9900
2:225408863:GGC:G	acceptor_gain	0.9900
2:225409101:GGTA:G	donor_loss	0.9900
2:225409102:GTA:G	donor_loss	0.9900
2:225409103:T:A	donor_loss	0.9900
2:225513370:GCATA:G	acceptor_gain	0.9900
2:225513636:GCCA:G	donor_gain	0.9900
2:225513640:G:GG	donor_gain	0.9900
2:225581939:A:AG	acceptor_gain	0.9900
2:225581940:G:GG	acceptor_gain	0.9900
2:225581940:GC:G	acceptor_gain	0.9900
2:225581940:GCGTC:G	acceptor_gain	0.9900
2:225583032:GAGA:G	donor_gain	0.9900
2:225583036:G:GG	donor_gain	0.9900
2:225626914:C:G	acceptor_gain	0.9900
2:225626915:A:AG	acceptor_gain	0.9900
2:225626916:G:GG	acceptor_gain	0.9900
2:225408859:T:TA	acceptor_gain	0.9800
2:225408862:AG:A	acceptor_gain	0.9800
2:225408863:GG:G	acceptor_gain	0.9800

AlphaMissense

4735 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:225513583:G:C	R145T	1.000
2:225513583:G:T	R145M	1.000
2:225513584:G:C	R145S	1.000
2:225513584:G:T	R145S	1.000
2:225582154:T:A	I246N	1.000
2:225582154:T:G	I246S	1.000
2:225582160:T:C	M248T	1.000
2:225582160:T:G	M248R	1.000
2:225582161:G:A	M248I	1.000
2:225582161:G:C	M248I	1.000
2:225582161:G:T	M248I	1.000
2:225582217:T:A	V267D	1.000
2:225582219:T:C	Y268H	1.000
2:225582229:T:C	M271T	1.000
2:225582230:G:A	M271I	1.000
2:225582230:G:C	M271I	1.000
2:225582230:G:T	M271I	1.000
2:225582393:T:C	F326L	1.000
2:225582395:C:A	F326L	1.000
2:225582395:C:G	F326L	1.000
2:225408959:G:A	G27R	0.999
2:225408959:G:C	G27R	0.999
2:225408971:T:G	Y31D	0.999
2:225408984:T:A	V35D	0.999
2:225408995:G:C	A39P	0.999
2:225409007:G:C	A43P	0.999
2:225409011:G:C	R44P	0.999
2:225513573:A:G	K142E	0.999
2:225513575:A:C	K142N	0.999
2:225513575:A:T	K142N	0.999

dbSNP variants (sampled 300 via entrez): RS1000012743 (2:225488152 G>A,C), RS1000017511 (2:225427612 T>C), RS1000031303 (2:225460174 C>T), RS1000034737 (2:225417500 C>G), RS1000082151 (2:225547107 C>T), RS1000092782 (2:225665836 A>G), RS1000125066 (2:225597343 T>C), RS1000128266 (2:225670934 A>T), RS1000140593 (2:225604714 TA>T), RS1000140686 (2:225658521 T>G), RS1000147470 (2:225513949 A>G), RS1000154238 (2:225427956 C>T), RS1000163130 (2:225461567 T>C), RS1000177948 (2:225522157 TTC>T), RS1000178343 (2:225597793 T>A,C)

Disease associations

OMIM: gene MIM:615478 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST001810_8	Menopause (age at onset)	3.000000e-07
GCST003658_2	Modified Stumvoll Insulin Sensitivity Index (model adjusted for BMI)	1.000000e-11
GCST003659_1	Modified Stumvoll Insulin Sensitivity Index (BMI interaction)	9.000000e-11
GCST003672_5	Docetaxel-induced peripheral neuropathy in metastatic castrate-resistant prostate cancer	3.000000e-06
GCST004029_28	Angiotensin-converting enzyme inhibitor intolerance	7.000000e-06
GCST004750_66	Squamous cell lung carcinoma	6.000000e-06
GCST005159_1	Insulin levels in response to oral glucose tolerance test (fasting)	2.000000e-07
GCST006463_5	Urinary albumin excretion (no hypertensive medication)	7.000000e-11
GCST006940_67	Neurociticism	2.000000e-08
GCST007327_99	Smoking status (ever vs never smokers)	1.000000e-09
GCST007718_5	Urinary albumin-to-creatinine ratio	7.000000e-26
GCST009640_14	Urinary albumin-to-creatinine ratio	3.000000e-17
GCST010242_87	HDL cholesterol levels	3.000000e-08
GCST010396_297	Gut microbiota (bacterial taxa, hurdle binary method)	9.000000e-08
GCST011122_39	Walking pace	4.000000e-10
GCST011365_25	Myocardial infarction	2.000000e-08
GCST011616_40	Cortical volume	6.000000e-11
GCST011741_71	LDL cholesterol levels in HIV infection	4.000000e-06
GCST011742_41	Triglyceride levels in HIV infection	7.000000e-07
GCST90011898_94	Alanine aminotransferase levels	2.000000e-20
GCST90011899_53	Aspartate aminotransferase levels	8.000000e-09

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0004704	age at menopause
EFO:0004340	body mass index
EFO:0004471	insulin sensitivity measurement
EFO:0005325	response to angiotensin-converting enzyme inhibitor
EFO:0004307	glucose tolerance test
EFO:0004467	insulin measurement
EFO:0004285	albuminuria
EFO:0007660	neuroticism measurement
EFO:0004318	smoking behavior
EFO:0007778	urinary albumin to creatinine ratio
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0007874	gut microbiome measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation	2
bisphenol F	affects cotreatment, increases methylation	1
sulforaphane	decreases expression	1
sodium arsenite	decreases expression	1
coumarin	affects phosphorylation	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Lead	affects expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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