GAP43

Summary

GAP43 (growth associated protein 43, HGNC:4140) is a protein-coding gene on chromosome 3q13.31, encoding Neuromodulin (P17677). This protein is associated with nerve growth.

The protein encoded by this gene has been termed a ‘growth’ or ‘plasticity’ protein because it is expressed at high levels in neuronal growth cones during development and axonal regeneration. This protein is considered a crucial component of an effective regenerative response in the nervous system. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.

Source: NCBI Gene 2596 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 54 total — 1 pathogenic, 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_002045

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4140
Approved symbol	GAP43
Name	growth associated protein 43
Location	3q13.31
Locus type	gene with protein product
Status	Approved
Aliases	B-50, PP46, GAP-43
Ensembl gene	ENSG00000172020
Ensembl biotype	protein_coding
OMIM	162060
Entrez	2596

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000305124, ENST00000393780, ENST00000857848, ENST00000920584

RefSeq mRNA: 2 — MANE Select: NM_002045 NM_001130064, NM_002045

CCDS: CCDS33830, CCDS46890

Canonical transcript exons

ENST00000305124 — 3 exons

Exon	Start	End
ENSE00000000158	115720794	115721483
ENSE00001174831	115676013	115676610
ENSE00001906692	115623510	115623719

Expression profiles

Bgee: expression breadth ubiquitous, 209 present calls, max score 99.66.

FANTOM5 (CAGE): breadth broad, TPM avg 19.9927 / max 6817.9668, expressed in 535 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
38042	7.8824	436
38044	7.3382	378
38041	2.4433	237
38038	1.5492	247
38039	0.5596	182
38040	0.1813	82
38043	0.0388	23

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
frontal pole	UBERON:0002795	99.66	gold quality
Brodmann (1909) area 10	UBERON:0013541	99.66	gold quality
cortical plate	UBERON:0005343	99.52	gold quality
right frontal lobe	UBERON:0002810	99.41	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.41	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.40	gold quality
superior frontal gyrus	UBERON:0002661	99.38	gold quality
frontal cortex	UBERON:0001870	99.35	gold quality
orbitofrontal cortex	UBERON:0004167	99.32	gold quality
prefrontal cortex	UBERON:0000451	99.31	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.19	gold quality
cingulate cortex	UBERON:0003027	99.17	gold quality
anterior cingulate cortex	UBERON:0009835	99.16	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.15	gold quality
neocortex	UBERON:0001950	99.11	gold quality
cerebral cortex	UBERON:0000956	98.96	gold quality
parietal lobe	UBERON:0001872	98.93	gold quality
temporal lobe	UBERON:0001871	98.88	gold quality
amygdala	UBERON:0001876	98.88	gold quality
entorhinal cortex	UBERON:0002728	98.88	gold quality
middle temporal gyrus	UBERON:0002771	98.87	gold quality
postcentral gyrus	UBERON:0002581	98.83	gold quality
endothelial cell	CL:0000115	98.76	gold quality
hypothalamus	UBERON:0001898	98.64	gold quality
cerebellar vermis	UBERON:0004720	98.61	gold quality
cerebellar cortex	UBERON:0002129	98.60	gold quality
cerebellar hemisphere	UBERON:0002245	98.59	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.58	gold quality
cerebellum	UBERON:0002037	98.57	gold quality
nucleus accumbens	UBERON:0001882	98.46	gold quality

Single-cell (SCXA)

Detected in 16 experiment(s), a significant marker in 15.

Experiment	Marker?	Max mean expression
E-MTAB-9154	yes	3422.44
E-MTAB-11121	yes	2954.70
E-HCAD-5	yes	2534.73
E-MTAB-8221	yes	2334.86
E-MTAB-6911	yes	2315.35
E-MTAB-8894	yes	2174.45
E-MTAB-9435	yes	2165.98
E-MTAB-10485	yes	1733.39
E-GEOD-98556	yes	1220.10
E-GEOD-93593	yes	752.97
E-GEOD-75140	yes	671.86
E-MTAB-8271	yes	343.22
E-HCAD-25	yes	81.57
E-GEOD-84465	yes	26.31
E-HCAD-10	yes	6.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ANKRD11, AP1, CEBPB, CREB1, EZH2, FUBP1, ID2, LITAF, NEUROD1, NEUROD2, NEUROD6, NFATC4, NR2F1, STAT3, TCF12, TCF3, TP53

miRNA regulators (miRDB)

62 targeting GAP43, 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-3064-3P	100.00	70.09	1254
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-12121	99.99	66.64	255
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-4452	99.50	68.45	1493
HSA-MIR-4696	99.48	67.48	1040
HSA-MIR-766-5P	99.47	67.91	2225

Literature-anchored findings (GeneRIF, showing 40)

• chemical analysis of fatty acylated species in GAP43 (PMID:12105219)
• In the dermis, there were fewer GAP-43 nerve fibers than PGP 9.5 fibers, whereas in the epidermis the numbers were equal. Only some Merkel cells and Meissner corpuscles were GAP-43-immunoreactive. (PMID:12704705)
• Data show that GAP43 acts as an osmosensory protein that augments internal calcium in response to hypotonicity. (PMID:12805215)
• Schizophrenia had significant decreases in GAP-43 immunoreactivity in the hilus (p<0.05, paired t-test) and inner molecular layer (p<0.05, paired t-test) but not in the outer molecular layer. In the same tissues. (PMID:15694236)
• Growth-associated protein 43, a marker of neural outgrowth and regeneration, is expressed in endometriosis-associated nerve fibers but not in existing peritoneal nerves. (PMID:17412328)
• HuD plays a role in the post-transcriptional control of GAP-43 mRNA (PMID:17577668)
• Data show that functional cooperation between TrkA and p75(NTR) accelerates neuronal differentiation by increased transcription of GAP-43 and p21(CIP/WAF) genes via ERK1/2 and AP-1 activities. (PMID:17619016)
• Around 1 month post lesion, degeneration at the cochlear nuclei progressively disappeared and a relevant GAP-43 expression was found. (PMID:19593683)
• Results indicate that there is no strong and direct interaction between POP and GAP43 at physiological conditions. (PMID:20869470)
• Results demonstrate that APT-2 is the protein thioesterase involved in the acylation/deacylation cycle operating in GAP-43 subcellular distribution. (PMID:21152083)
• Through MEK/ERK pathway, S1P stimulates GAP43 transcription with increased binding of C/EBPbeta to the 5’-promoter (PMID:21769916)
• The results of this study supported to the hypothesis of multiple rare mutations in schizophrenia, and it provides genetic clues that indicate the involvement of GAP-43 in this disorder. (PMID:22138049)
• Impaired regeneration of intra-epidermal C fibers in the early stages of type 2 diabetes mellitus, as indicated by GAP-43 expression, might be a marker of incipient diabetic neuropathy. (PMID:22209024)
• immunostaning for GAP-43 was relatively similar in ganglionic versus aganglionic colon. (PMID:23153097)
• Dynamic palmitoylation links cytosol-membrane shuttling of acyl-protein thioesterase-1 and acyl-protein thioesterase-2 with that of proto-oncogene H-ras product and growth-associated protein-43 (PMID:23396970)
• The results showed that the decreased GAP-43 levels induced by glutamate could be partially reversed by the presence of NRG-1beta (PMID:23524246)
• GAP43 is seemingly a highly sensitive marker for peripheral nerve sheath tumors (PMID:23887302)
• increased expression of TH and GAP43 might be a molecular mechanism for left atrial myoelectricity remodeling of aging atrial fibrillation patients, which might be potential therapeutic targets of atrial fibrillation. (PMID:24301786)
• Results show that PKC-dependent phosphorylation of GAP43 plays a critical role in regulating postsynaptic gephyrin aggregation in developing GABAergic synapses. (PMID:25755278)
• The peripheral neuropathies lead to an initial increase in GAP-43 gene expression as a potential mechanism of regeneration, which is not sustained in neuropathies of long duration. (PMID:26071889)
• The expression pattern of the regeneration-associated protein GAP-43 suggested a lower regenerative capacity in nigral dopaminergic neurons of Parkinson disease patients. (PMID:26748453)
• Copy-number variations are enriched for GAP43 and other neurodevelopmental genes in children with developmental coordination disorder. (PMID:27489308)
• Downregulation of GAP43 promotes gliomas. (PMID:27495233)
• associations of neuromodulin and neurogranin to Alzheimer’s disease (PMID:27604409)
• Findings show high level of both YKL-40 and GAP-43 in CSF of older women with suicidal ideation which suggest that a disrupted synaptic glial functioning and inflammation may be related to the aetiology of suicidal ideation in older adults. (PMID:28211584)
• GAL, GAP43 and NRSN1 single nucleotide polymorphisms and related gene-gene interaction networks might be involved in the altered susceptibility to Hirschsprung disease in the Han Chinese population. (PMID:29654647)
• We found an increased expression of Nestin and GAP43 (growth associated protein 43) in treated cells. In conclusion, Periodontal ligament mesenchymal stem cells (hPDLSCs) treated with Moringin and Cannabidiol showed an improved survival capacity and neuronal differentiation potential (PMID:30096889)
• GAP43 is an independent predictor of non-small cell lung cancer brain metastasis. (PMID:30419922)
• Growth-associated protein 43 promotes thyroid cancer cell lines progression via epithelial-mesenchymal transition. (PMID:31568662)
• Cerebrospinal fluid growth-associated protein 43 in multiple sclerosis. (PMID:31754174)
• Transcriptome profiling unveils GAP43 regulates ABC transporters and EIF2 signaling in colorectal cancer cells. (PMID:33402155)
• The advanced development of Cx43 and GAP-43 mediated intercellular networking in IDH1 wildtype diffuse and anaplastic gliomas with lower mitotic rate. (PMID:34173871)
• Prognostic value of cutaneous reinnervation with GAP-43 in oxaliplatin-induced neuropathy. (PMID:35258850)
• Cutaneous expression of growth-associated protein 43 is not a compelling marker for human nerve regeneration in carpal tunnel syndrome. (PMID:36383568)
• Association of CSF GAP-43 and APOE epsilon4 with Cognition in Mild Cognitive Impairment and Alzheimer’s Disease. (PMID:36611808)
• Impact of GAP-43, Cx43 and actin expression on the outcome and overall survival in diffuse and anaplastic gliomas. (PMID:36739296)
• Growth associated protein 43 deficiency promotes podocyte injury by activating the calmodulin/calcineurin pathway under hyperglycemia. (PMID:36963347)
• GAP43-dependent mitochondria transfer from astrocytes enhances glioblastoma tumorigenicity. (PMID:37169842)
• Association of APOE-epsilon4 and GAP-43-related presynaptic loss with beta-amyloid, tau, neurodegeneration, and cognitive decline. (PMID:37852045)
• Associations of Growth-Associated Protein 43 with Cerebral Microbleeds: A Longitudinal Study. (PMID:38339928)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gap43	ENSDARG00000099744
mus_musculus	Gap43	ENSMUSG00000047261
rattus_norvegicus	Gap43	ENSRNOG00000001528

Paralogs (2): SPA17 (ENSG00000064199), RIIAD1 (ENSG00000178796)

Protein

Protein identifiers

Neuromodulin — P17677 (reviewed: P17677)

Alternative names: Axonal membrane protein GAP-43, Growth-associated protein 43, Neural phosphoprotein B-50, pp46

All UniProt accessions (2): P17677, Q5U058

UniProt curated annotations — full annotation on UniProt →

Function. This protein is associated with nerve growth. It is a major component of the motile ‘growth cones’ that form the tips of elongating axons. Plays a role in axonal and dendritic filopodia induction.

Subunit / interactions. Identified in a complex containing FGFR4, NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 and CTTN. Interacts (via IQ domain) with calmodulin. Binds calmodulin with a greater affinity in the absence of Ca(2+) than in its presence.

Subcellular location. Cell membrane. Cell projection. Growth cone membrane. Synapse. Filopodium membrane. Perikaryon. Dendrite. Axon. Cytoplasm.

Post-translational modifications. Phosphorylated. Phosphorylation of this protein by a protein kinase C is specifically correlated with certain forms of synaptic plasticity. Palmitoylated by ZDHHC3. Palmitoylation is regulated by ARF6 and is essential for plasma membrane association and axonal and dendritic filopodia induction. Deacylated by LYPLA2.

Similarity. Belongs to the neuromodulin family.

Isoforms (2)

UniProt ID	Names	Canonical?
P17677-1	1	yes
P17677-2	2

RefSeq proteins (2): NP_001123536, NP_002036* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000048	IQ_motif_EF-hand-BS	Binding_site
IPR001422	Neuromodulin	Family
IPR017454	Neuromodulin_C	Domain
IPR018243	Neuromodulin_palmitoyl_site	PTM
IPR018947	Neuromodulin_N	Domain
IPR033137	Neuromodulin_P_site	PTM

Pfam: PF00612, PF06614, PF10580

UniProt features (26 total): compositionally biased region 10, modified residue 7, lipid moiety-binding region 2, sequence variant 2, chain 1, domain 1, region of interest 1, splice variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P17677-F1	56.00	0.09

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 (9): 41, 151, 153, 154, 181, 202, 203, 3, 4

Mutagenesis-validated functional residues (1):

Position	Phenotype
3–4	inhibits axonal and dendritic filopodia formation and reduces dendritic and axonal branching.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-373760	L1CAM interactions
R-HSA-1266738	Developmental Biology
R-HSA-422475	Axon guidance
R-HSA-9675108	Nervous system development

MSigDB gene sets: 259 (showing top): GNF2_RTN1, GOBP_NEURON_RECOGNITION, GOBP_SYNAPSE_ASSEMBLY, TTCCGTT_MIR191, GOBP_GROWTH, GOBP_REGENERATION, GOBP_NEUROGENESIS, CHX10_01, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GGGTGGRR_PAX4_03, CAGCTG_AP4_Q5, MODULE_66, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_CELL_JUNCTION_ORGANIZATION, MODULE_289

GO Biological Process (15): phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), response to wounding (GO:0009611), response to auditory stimulus (GO:0010996), axon choice point recognition (GO:0016198), axon regeneration (GO:0031103), regulation of growth (GO:0040008), tissue regeneration (GO:0042246), cell fate commitment (GO:0045165), astrocyte differentiation (GO:0048708), regulation of filopodium assembly (GO:0051489), radial glial cell differentiation (GO:0060019), regulation of postsynaptic specialization assembly (GO:0099150), nervous system development (GO:0007399), axon guidance (GO:0007411), cell differentiation (GO:0030154)

GO Molecular Function (5): phosphatidylserine binding (GO:0001786), calmodulin binding (GO:0005516), lysophosphatidic acid binding (GO:0035727), phosphatidylinositol phosphate binding (GO:1901981), protein binding (GO:0005515)

GO Cellular Component (14): cytoplasm (GO:0005737), plasma membrane (GO:0005886), postsynaptic density (GO:0014069), dendrite (GO:0030425), filopodium membrane (GO:0031527), growth cone membrane (GO:0032584), perikaryon (GO:0043204), presynapse (GO:0098793), GABA-ergic synapse (GO:0098982), membrane (GO:0016020), axon (GO:0030424), cell projection (GO:0042995), synapse (GO:0045202), cell periphery (GO:0071944)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Axon guidance	1
Nervous system development	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
phospholipid binding	3
cellular developmental process	2
glial cell differentiation	2
anion binding	2
neuron projection	2
synapse	2
G protein-coupled receptor signaling pathway	1
phospholipase C activator activity	1
response to stress	1
response to mechanical stimulus	1
axon guidance	1
neuron recognition	1
neuron projection regeneration	1
response to axon injury	1
axon development	1
growth	1
regulation of biological process	1
regeneration	1
developmental growth	1
cell differentiation	1
central nervous system development	1
filopodium assembly	1
regulation of plasma membrane bounded cell projection assembly	1
postsynaptic specialization assembly	1
regulation of organelle assembly	1
system development	1
axonogenesis	1
neuron projection guidance	1
modified amino acid binding	1
protein binding	1
carbohydrate derivative binding	1
binding	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
asymmetric synapse	1
postsynaptic specialization	1
dendritic tree	1
filopodium	1

Protein interactions and networks

STRING

2890 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GAP43	CALML6	Q8TD86	987
GAP43	CALML3	P27482	987
GAP43	CALML5	Q9NZT1	987
GAP43	CALML4	Q96GE6	987
GAP43	CALM1	P02593	983
GAP43	NGF	P01138	905
GAP43	BASP1	P80723	890
GAP43	SYN1	P17600	886
GAP43	SYP	P08247	854
GAP43	NRGN	Q92686	833
GAP43	NCAM1	P13591	809
GAP43	MAP2	P11137	771
GAP43	OMP	P47874	769
GAP43	SNAP25	P13795	750
GAP43	BDNF	P23560	743

IntAct

62 interactions, top by confidence:

A	B	Type	Score
MED21	MED19	psi-mi:“MI:0914”(association)	0.880
BIRC2	HTRA2	psi-mi:“MI:0914”(association)	0.650
KIFAP3	KIF3C	psi-mi:“MI:0914”(association)	0.640
PRKCD	GAP43	psi-mi:“MI:0217”(phosphorylation reaction)	0.600
GAP43	PRKCD	psi-mi:“MI:0915”(physical association)	0.600
PRKCD	GAP43	psi-mi:“MI:0915”(physical association)	0.600
GAP43	DRD4	psi-mi:“MI:0915”(physical association)	0.560
S1PR2	PALM3	psi-mi:“MI:0914”(association)	0.530
GJB7	PALM3	psi-mi:“MI:0914”(association)	0.530
SLC25A41	NUDT19	psi-mi:“MI:0914”(association)	0.530
GDE1	GAPDHS	psi-mi:“MI:0914”(association)	0.530
CCNL2	ZBTB43	psi-mi:“MI:0914”(association)	0.530
TMEM185A	TSPAN6	psi-mi:“MI:0914”(association)	0.530
TIGD5	P4HA2	psi-mi:“MI:0914”(association)	0.530
PCK2	IGHA1	psi-mi:“MI:0914”(association)	0.530
MARVELD2	GAP43	psi-mi:“MI:0914”(association)	0.530
APP	GAP43	psi-mi:“MI:0915”(physical association)	0.500
GAP43	PSEN1	psi-mi:“MI:0914”(association)	0.420
PSEN1	GAP43	psi-mi:“MI:2364”(proximity)	0.420
APP	GAP43	psi-mi:“MI:0915”(physical association)	0.400
MAPT	MEX3A	psi-mi:“MI:0914”(association)	0.350
APP	RTL1	psi-mi:“MI:0914”(association)	0.350

BioGRID (56): GAP43 (Affinity Capture-MS), GAP43 (Affinity Capture-MS), GAP43 (Affinity Capture-MS), GAP43 (Affinity Capture-MS), GAP43 (Affinity Capture-MS), GAP43 (Affinity Capture-MS), GAP43 (Affinity Capture-MS), GAP43 (Affinity Capture-MS), GAP43 (Affinity Capture-MS), GAP43 (Affinity Capture-MS), GAP43 (Affinity Capture-MS), GAP43 (Affinity Capture-MS), GAP43 (Affinity Capture-MS), GAP43 (Affinity Capture-MS), GAP43 (Affinity Capture-MS)

ESM2 similar proteins: B0WQG0, F4K4Y5, O65370, P01252, P02316, P04550, P05114, P06302, P06454, P06837, P07936, P12274, P12902, P16527, P17677, P17691, P23614, P26350, P31168, P33191, P35001, P42759, P42763, P43393, P46524, P55860, P80723, P80724, Q05175, Q10020, Q17Q32, Q1RM09, Q39967, Q3ZBV4, Q56WK6, Q56ZI2, Q5IS67, Q5NVP7, Q5R790, Q5U274

Diamond homologs: P06836, P06837, P07936, P17677, P17691, P35001, P55860, Q5IS67, Q5NVP7, Q6S9D9, Q95K78, Q98987, O62770, P35722, P54866, P54877, P60761, Q04940, Q92686

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
LYPLA2	“down-regulates quantity by destabilization”	GAP43	deacetylation
ANKRD11	“up-regulates quantity by expression”	GAP43	“transcriptional regulation”
GAP43	up-regulates	Neurite_outgrowth
NfKb-p65/p50	“up-regulates quantity by expression”	GAP43	“transcriptional regulation”
GAP43	up-regulates	Neurogenesis
STAT3	“up-regulates quantity by expression”	GAP43	“transcriptional regulation”
PRKCB	unknown	GAP43	phosphorylation
CSNK2A1	unknown	GAP43	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 65 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
axonogenesis	5	14.6×	4e-03
negative regulation of gene expression	7	8.8×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	44
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
149415	GRCh38/hg38 3q13.2-13.31(chr3:112465094-115774111)x1	Pathogenic
253338	GRCh37/hg19 3q13.31(chr3:114260384-116691114)x1	Likely pathogenic

SpliceAI

1237 predictions. Top by Δscore:

Variant	Effect	Δscore
3:115676005:C:CA	acceptor_gain	1.0000
3:115676009:A:AG	acceptor_gain	1.0000
3:115676009:AAAG:A	acceptor_gain	1.0000
3:115676010:A:G	acceptor_gain	1.0000
3:115720792:A:AG	acceptor_gain	1.0000
3:115720793:G:GG	acceptor_gain	1.0000
3:115720793:GAA:G	acceptor_gain	1.0000
3:115631247:A:AG	acceptor_gain	0.9900
3:115631248:G:GG	acceptor_gain	0.9900
3:115676005:C:A	acceptor_loss	0.9900
3:115676008:CAAA:C	acceptor_loss	0.9900
3:115676011:A:C	acceptor_loss	0.9900
3:115676011:A:G	acceptor_gain	0.9900
3:115676011:AG:A	acceptor_gain	0.9900
3:115676011:AGGTT:A	acceptor_gain	0.9900
3:115676012:G:A	acceptor_gain	0.9900
3:115676012:G:GG	acceptor_gain	0.9900
3:115676012:G:GT	acceptor_loss	0.9900
3:115676012:GGTT:G	acceptor_gain	0.9900
3:115676012:GGTTG:G	acceptor_gain	0.9900
3:115676611:G:GC	donor_loss	0.9900
3:115676612:T:G	donor_loss	0.9900
3:115720775:ATCTT:A	acceptor_gain	0.9900
3:115720776:T:G	acceptor_gain	0.9900
3:115720779:T:TA	acceptor_gain	0.9900
3:115720789:CTCAG:C	acceptor_loss	0.9900
3:115720790:TCAGA:T	acceptor_loss	0.9900
3:115720792:A:AC	acceptor_loss	0.9900
3:115720793:G:A	acceptor_loss	0.9900
3:115720793:GA:G	acceptor_gain	0.9900

AlphaMissense

1562 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:115676095:T:A	I38N	1.000
3:115676095:T:C	I38T	1.000
3:115676095:T:G	I38S	1.000
3:115676100:G:C	A40P	1.000
3:115676106:T:C	F42L	1.000
3:115676107:T:C	F42S	1.000
3:115676107:T:G	F42C	1.000
3:115676108:C:A	F42L	1.000
3:115676108:C:G	F42L	1.000
3:115676109:C:A	R43S	1.000
3:115676113:G:A	G44E	1.000
3:115676115:C:G	H45D	1.000
3:115676125:G:C	R48T	1.000
3:115676125:G:T	R48M	1.000
3:115676126:G:C	R48S	1.000
3:115676126:G:T	R48S	1.000
3:115676099:G:C	Q39H	0.999
3:115676099:G:T	Q39H	0.999
3:115676110:G:C	R43P	0.999
3:115676112:G:A	G44R	0.999
3:115676112:G:C	G44R	0.999
3:115676116:A:C	H45P	0.999
3:115676117:C:A	H45Q	0.999
3:115676117:C:G	H45Q	0.999
3:115676085:G:C	A35P	0.998
3:115676086:C:A	A35E	0.998
3:115676091:A:G	K37E	0.998
3:115676093:A:C	K37N	0.998
3:115676093:A:T	K37N	0.998
3:115676101:C:A	A40D	0.998

dbSNP variants (sampled 300 via entrez): RS1000027277 (3:115714040 G>A,C), RS1000043573 (3:115661845 T>A), RS1000044539 (3:115629078 C>A), RS1000076106 (3:115662103 G>A), RS1000097371 (3:115706966 G>A), RS1000167419 (3:115688466 A>C,T), RS1000167686 (3:115642977 C>T), RS1000176266 (3:115693616 G>A), RS1000249108 (3:115657375 T>A), RS1000256403 (3:115630024 C>T), RS1000261954 (3:115688671 G>A,T), RS1000417102 (3:115668687 G>A,C), RS1000424688 (3:115651102 A>G), RS1000491570 (3:115629676 C>A), RS1000523542 (3:115708806 A>C)

Disease associations

OMIM: gene MIM:162060 | 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
GCST001585_8	Breast size	8.000000e-06
GCST002828_21	Urate levels in obese individuals	5.000000e-06
GCST003469_1	Response to cognitive-behavioural therapy in anxiety disorder	6.000000e-06
GCST004641_16	Borderline personality disorder	7.000000e-06
GCST007102_10	Seasonality and depression	2.000000e-06
GCST008668_3	Proliferative diabetic retinopathy	3.000000e-06
GCST009391_1131	Metabolite levels	2.000000e-07
GCST009391_957	Metabolite levels	1.000000e-06

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0007820	cognitive behavioural therapy
EFO:0006876	seasonality measurement
EFO:0010489	glycerophosphocholine measurement
EFO:0010444	triacylglycerol 60:12 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066951 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.29	Kd	51.53	nM	CHEMBL5653589
7.29	ED50	51.53	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148413: Binding affinity to human GAP43 incubated for 45 mins by Kinobead based pull down assay	kd	0.0515	uM

CTD chemical–gene interactions

71 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	10
Tretinoin	increases expression	4
trichostatin A	affects cotreatment, increases expression	3
entinostat	increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	2
belinostat	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
moringin	affects cotreatment, increases expression	1
aminomethylphosphonic acid (AMPA)	decreases expression	1
mipafox	decreases expression	1
bisphenol A	decreases expression	1
lead acetate	affects cotreatment, decreases expression, increases abundance, increases reaction	1
salinomycin	decreases expression	1
oxadiazon	affects reaction, decreases reaction, increases expression	1
cypermethrin	increases expression	1
sodium arsenite	increases expression	1
benzo(e)pyrene	increases methylation	1
Ashwagandha	decreases expression, decreases reaction	1
tryptanthrine	increases expression	1
cyfluthrin	increases expression	1
isophthalate	decreases reaction, increases expression	1
Go 6976	decreases reaction, increases expression	1
azoxystrobin	decreases expression	1
CGP 52608	increases reaction, affects binding	1
deguelin	decreases expression	1
fenpyroximate	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
pyrimidifen	decreases expression	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651455	Binding	Binding affinity to human GAP43 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

1 cell lines: 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_UL58	NCBSi002-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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