NYAP1

Summary

NYAP1 (neuronal tyrosine phosphorylated phosphoinositide-3-kinase adaptor 1, HGNC:22009) is a protein-coding gene on chromosome 7q22.1, encoding Neuronal tyrosine-phosphorylated phosphoinositide-3-kinase adapter 1 (Q6ZVC0). 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 222950 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 166 total
• MANE Select transcript: NM_173564

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22009
Approved symbol	NYAP1
Name	neuronal tyrosine phosphorylated phosphoinositide-3-kinase adaptor 1
Location	7q22.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ37538
Ensembl gene	ENSG00000166924
Ensembl biotype	protein_coding
OMIM	615477
Entrez	222950

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000300179, ENST00000454988, ENST00000489641, ENST00000496985, ENST00000880488, ENST00000880489

RefSeq mRNA: 1 — MANE Select: NM_173564 NM_173564

CCDS: CCDS5696

Canonical transcript exons

ENST00000300179 — 7 exons

Exon	Start	End
ENSE00001107823	100490517	100490729
ENSE00001266154	100493646	100494802
ENSE00001266160	100488152	100489666
ENSE00001365731	100486821	100487182
ENSE00001371485	100483927	100484001
ENSE00001374480	100485228	100485379
ENSE00003605670	100490986	100491095

Expression profiles

Bgee: expression breadth ubiquitous, 159 present calls, max score 94.80.

FANTOM5 (CAGE): breadth broad, TPM avg 2.8758 / max 96.1704, expressed in 564 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
79994	1.3425	425
79993	0.8059	279
79990	0.3272	101
79991	0.2543	87
79995	0.0896	49
79992	0.0564	27

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	94.80	gold quality
right frontal lobe	UBERON:0002810	90.37	gold quality
anterior cingulate cortex	UBERON:0009835	89.82	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.75	gold quality
prefrontal cortex	UBERON:0000451	89.46	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.56	gold quality
cerebellar hemisphere	UBERON:0002245	87.50	gold quality
cerebellar cortex	UBERON:0002129	87.34	gold quality
ganglionic eminence	UBERON:0004023	87.20	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	85.85	gold quality
hypothalamus	UBERON:0001898	85.42	gold quality
cerebellum	UBERON:0002037	85.07	gold quality
nucleus accumbens	UBERON:0001882	84.65	gold quality
adenohypophysis	UBERON:0002196	84.29	gold quality
neocortex	UBERON:0001950	84.20	gold quality
caudate nucleus	UBERON:0001873	84.08	gold quality
putamen	UBERON:0001874	83.50	gold quality
amygdala	UBERON:0001876	83.35	gold quality
pituitary gland	UBERON:0000007	82.87	gold quality
frontal cortex	UBERON:0001870	82.85	gold quality
cerebral cortex	UBERON:0000956	80.38	gold quality
ventricular zone	UBERON:0003053	80.23	gold quality
forebrain	UBERON:0001890	80.14	gold quality
primary visual cortex	UBERON:0002436	80.03	gold quality
brain	UBERON:0000955	79.97	gold quality
Ammon’s horn	UBERON:0001954	74.44	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	74.32	gold quality
right ovary	UBERON:0002118	73.67	gold quality
right testis	UBERON:0004534	73.45	gold quality
occipital lobe	UBERON:0002021	73.33	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.12

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

40 targeting NYAP1, 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-5193	100.00	67.26	1744
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-4318	99.38	66.94	1505
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-532-3P	99.34	65.76	1195
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-6749-3P	99.00	65.73	1443
HSA-MIR-6895-3P	98.79	65.69	996
HSA-MIR-6830-3P	98.62	68.07	1760
HSA-MIR-4691-5P	98.41	66.77	1343
HSA-MIR-6792-3P	98.41	66.86	1359
HSA-MIR-5088-3P	98.29	66.63	1310
HSA-MIR-4778-5P	97.96	68.06	1634
HSA-MIR-924	97.78	66.21	681
HSA-MIR-4799-3P	97.78	65.97	893

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000103123
mus_musculus	Nyap1	ENSMUSG00000045348
rattus_norvegicus	Nyap1	ENSRNOG00000024641

Paralogs (1): NYAP2 (ENSG00000144460)

Protein

Protein identifiers

Neuronal tyrosine-phosphorylated phosphoinositide-3-kinase adapter 1 — Q6ZVC0 (reviewed: Q6ZVC0)

All UniProt accessions (2): Q6ZVC0, C9JS30

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 (2)

UniProt ID	Names	Canonical?
Q6ZVC0-1	1	yes
Q6ZVC0-2	2

RefSeq proteins (1): NP_775835* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF15439, PF15452

UniProt features (18 total): compositionally biased region 9, region of interest 6, chain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZVC0-F1	49.14	0.02

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 91 (showing top): FREAC2_01, GOBP_NEUROGENESIS, TGACCTY_ERR1_Q2, FOXO4_01, GGGTGGRR_PAX4_03, COUP_01, GOBP_PHOSPHATIDYLINOSITOL_3_KINASE_PROTEIN_KINASE_B_SIGNAL_TRANSDUCTION, HNF4_01, USF_02, GOBP_CELL_PROJECTION_ORGANIZATION, AP2_Q6_01, TGACCTTG_SF1_Q6, AP2GAMMA_01, SPZ1_01, MARSON_BOUND_BY_FOXP3_UNSTIMULATED

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

GO Molecular Function (0):

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

Protein interactions and networks

STRING

938 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NYAP1	LRCOL1	A6NCL2	665
NYAP1	ZCWPW1	Q9H0M4	605
NYAP1	PILRB	Q9UKJ0	510
NYAP1	NYAP2	Q9P242	482
NYAP1	PILRA	Q9UKJ1	480
NYAP1	VGLL4	Q14135	479
NYAP1	MYO16	Q9Y6X6	476
NYAP1	IFT56	A0AVF1	469
NYAP1	BCORL1	Q5H9F3	469
NYAP1	NME8	Q8N427	465
NYAP1	PPP1R35	Q8TAP8	454
NYAP1	TSC22D4	Q9Y3Q8	450
NYAP1	SLC24A4	Q8NFF2	449
NYAP1	FAM180B	Q6P0A1	447
NYAP1	ABCA7	Q8IZY2	403

IntAct

8 interactions, top by confidence:

A	B	Type	Score
NYAP1	HCFC1	psi-mi:“MI:0915”(physical association)	0.400
NYAP1	PRX	psi-mi:“MI:0915”(physical association)	0.400
NYAP1	LMNA	psi-mi:“MI:0915”(physical association)	0.400
NYAP1	PIP5K1C	psi-mi:“MI:0915”(physical association)	0.400
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350
FYN	NYAP1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (16): 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), NYAP1 (Proximity Label-MS), NYAP1 (Proximity Label-MS), PRX (Proximity Label-MS), NYAP1 (Protein-peptide), NYAP1 (Affinity Capture-MS), NYAP1 (Proximity Label-MS), NYAP1 (Cross-Linking-MS (XL-MS)), NYAP1 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A2A7S8, A5D7K1, A5PK23, B1AXH1, F1QGH6, O94885, O95402, Q08495, Q08DM1, Q3T044, Q499V8, Q5HYW2, Q5PQP4, Q5R4B6, Q5R8Q8, Q5SYE7, Q5T0Z8, Q5U2R6, Q6PDH0, Q6PFX7, Q6PGN9, Q6ZVC0, Q7TT28, Q80U35, Q80VC9, Q80Z38, Q86UU1, Q86WR7, Q8BI29, Q8C5R2, Q8CAF4, Q8JZX9, Q8K4J6, Q8N1G1, Q8TF72, Q91Z58, Q969V6, Q96A73, Q9BW04, Q9D0P7

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	150
Likely benign	10
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

980 predictions. Top by Δscore:

Variant	Effect	Δscore
7:100485210:A:AG	acceptor_gain	1.0000
7:100485376:GGAG:G	donor_gain	1.0000
7:100485377:GAG:G	donor_gain	1.0000
7:100485377:GAGG:G	donor_gain	1.0000
7:100485377:GAGGT:G	donor_loss	1.0000
7:100485378:AGG:A	donor_loss	1.0000
7:100485380:G:C	donor_loss	1.0000
7:100485380:G:GG	donor_gain	1.0000
7:100488140:T:A	acceptor_gain	1.0000
7:100488147:TCCA:T	acceptor_loss	1.0000
7:100488148:CCAG:C	acceptor_loss	1.0000
7:100488149:CA:C	acceptor_loss	1.0000
7:100488150:A:AG	acceptor_gain	1.0000
7:100488151:G:A	acceptor_loss	1.0000
7:100488151:G:GG	acceptor_gain	1.0000
7:100490984:A:AG	acceptor_gain	1.0000
7:100490985:G:GG	acceptor_gain	1.0000
7:100493632:C:A	acceptor_gain	1.0000
7:100493638:C:CA	acceptor_gain	1.0000
7:100493639:G:A	acceptor_gain	1.0000
7:100493644:A:AG	acceptor_gain	1.0000
7:100493645:G:GA	acceptor_gain	1.0000
7:100493645:GCCC:G	acceptor_gain	1.0000
7:100493645:GCCCC:G	acceptor_gain	1.0000
7:100483998:CCAG:C	donor_loss	0.9900
7:100483999:CAG:C	donor_loss	0.9900
7:100484000:AGGTA:A	donor_loss	0.9900
7:100484002:G:GA	donor_loss	0.9900
7:100485203:C:A	acceptor_gain	0.9900
7:100485211:C:G	acceptor_gain	0.9900

AlphaMissense

5347 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:100488371:T:A	I217N	1.000
7:100493725:T:A	I783N	1.000
7:100493735:G:C	K786N	1.000
7:100493735:G:T	K786N	1.000
7:100493886:T:A	W837R	1.000
7:100493886:T:C	W837R	1.000
7:100493888:G:C	W837C	1.000
7:100493888:G:T	W837C	1.000
7:100493890:A:C	D838A	1.000
7:100493890:A:T	D838V	1.000
7:100493899:T:A	I841N	1.000
7:100485319:T:C	L3P	0.999
7:100486930:T:C	F60L	0.999
7:100486932:C:A	F60L	0.999
7:100486932:C:G	F60L	0.999
7:100488371:T:G	I217S	0.999
7:100488512:T:C	M264T	0.999
7:100488700:T:C	F327L	0.999
7:100488701:T:C	F327S	0.999
7:100488701:T:G	F327C	0.999
7:100488702:C:A	F327L	0.999
7:100488702:C:G	F327L	0.999
7:100488710:T:C	L330P	0.999
7:100493731:G:C	R785P	0.999
7:100493733:A:G	K786E	0.999
7:100493737:G:C	R787P	0.999
7:100493745:T:C	C790R	0.999
7:100493746:G:A	C790Y	0.999
7:100493747:C:G	C790W	0.999
7:100493755:T:C	I793T	0.999

dbSNP variants (sampled 300 via entrez): RS1000423028 (7:100493116 G>A,C), RS1000513451 (7:100482034 C>T), RS1000780836 (7:100492741 A>G), RS1000800040 (7:100490242 G>A), RS1000868194 (7:100488785 C>T), RS1001116528 (7:100483400 G>A,C), RS1001376733 (7:100494275 A>G), RS1001463227 (7:100483176 G>A), RS1002066184 (7:100484526 G>A,T), RS1002882914 (7:100490797 C>A), RS1003029772 (7:100485527 A>G), RS1003082133 (7:100485895 C>T), RS1003113785 (7:100482465 G>A), RS1003284262 (7:100492533 G>A), RS1003944794 (7:100492663 C>T)

Disease associations

OMIM: gene MIM:615477 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST002500_43	QT interval	1.000000e-07
GCST004604_120	Hematocrit	5.000000e-37
GCST004615_47	Hemoglobin concentration	7.000000e-36
GCST010002_259	Refractive error	3.000000e-16
GCST010083_269	Hemoglobin levels	5.000000e-82
GCST010702_48	Subcortical volume (MOSTest)	6.000000e-10
GCST010703_289	Brain morphology (MOSTest)	6.000000e-15
GCST010989_122	Body size at age 10	2.000000e-08

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004682	QT interval
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0004346	neuroimaging measurement
EFO:0009819	comparative body size at age 10, self-reported

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression	2
sotorasib	affects cotreatment, decreases expression	1
dimethylselenide	increases expression, increases oxidation	1
abrine	decreases expression	1
jinfukang	increases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Vorinostat	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Niclosamide	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	increases expression	1
Smoke	decreases expression	1
Testosterone	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Reactive Oxygen Species	increases expression, increases oxidation	1

Clinical trials (associated diseases)

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