GRIPAP1

Summary

GRIPAP1 (GRIP1 associated protein 1, HGNC:18706) is a protein-coding gene on chromosome Xp11.23, encoding GRIP1-associated protein 1 (Q4V328). Regulates the endosomal recycling back to the neuronal plasma membrane, possibly by connecting early and late recycling endosomal domains and promoting segregation of recycling endosomes from early endosomal membranes.

This gene encodes a guanine nucleotide exchange factor for the Ras family of small G proteins (RasGEF). The encoded protein interacts in a complex with glutamate receptor interacting protein 1 (GRIP1) and plays a role in the regulation of AMPA receptor function.

Source: NCBI Gene 56850 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 153 total
• MANE Select transcript: NM_020137

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18706
Approved symbol	GRIPAP1
Name	GRIP1 associated protein 1
Location	Xp11.23
Locus type	gene with protein product
Status	Approved
Aliases	GRASP-1, GRASP1, KIAA1167, MPMGp800B12492Q3, DKFZp434P0630
Ensembl gene	ENSG00000068400
Ensembl biotype	protein_coding
OMIM	300408
Entrez	56850

Gene structure

Transcript identifiers

Ensembl transcripts: 124 — 61 protein_coding, 39 retained_intron, 22 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000376423, ENST00000473581, ENST00000474512, ENST00000480041, ENST00000488361, ENST00000495258, ENST00000593475, ENST00000611705, ENST00000611757, ENST00000617369, ENST00000619107, ENST00000619149, ENST00000621664, ENST00000622599, ENST00000703854, ENST00000703855, ENST00000703859, ENST00000703860, ENST00000703861, ENST00000703862, ENST00000703874, ENST00000703875, ENST00000703876, ENST00000703877, ENST00000703878, ENST00000703879, ENST00000703880, ENST00000703881, ENST00000703882, ENST00000703883, ENST00000703884, ENST00000703885, ENST00000703886, ENST00000703887, ENST00000703905, ENST00000703906, ENST00000703925, ENST00000703926, ENST00000703927, ENST00000703928, ENST00000703929, ENST00000703930, ENST00000703931, ENST00000703932, ENST00000703933, ENST00000703934, ENST00000703935, ENST00000703958, ENST00000703959, ENST00000703960, ENST00000703961, ENST00000703962, ENST00000703963, ENST00000703964, ENST00000703988, ENST00000703989, ENST00000703990, ENST00000703991, ENST00000703992, ENST00000703993, ENST00000703994, ENST00000703995, ENST00000704017, ENST00000704018, ENST00000704019, ENST00000704020, ENST00000704021, ENST00000704022, ENST00000704028, ENST00000704029, ENST00000704030, ENST00000704031, ENST00000704032, ENST00000704033, ENST00000704034, ENST00000704035, ENST00000704036, ENST00000704037, ENST00000704038, ENST00000704039, ENST00000704044, ENST00000704045, ENST00000704046, ENST00000704047, ENST00000704048, ENST00000704095, ENST00000704096, ENST00000704097, ENST00000704098, ENST00000704103, ENST00000704104, ENST00000704105, ENST00000704106, ENST00000704107, ENST00000704108, ENST00000704263, ENST00000704264, ENST00000704265, ENST00000704266, ENST00000704267, ENST00000704268, ENST00000704269, ENST00000704270, ENST00000704271, ENST00000704272, ENST00000704273, ENST00000704792, ENST00000900845, ENST00000900846, ENST00000900847, ENST00000900848, ENST00000900849, ENST00000900850, ENST00000900851, ENST00000900852, ENST00000900853, ENST00000937301, ENST00000946827, ENST00000946828, ENST00000946829, ENST00000946830, ENST00000946831, ENST00000946832, ENST00000946833

RefSeq mRNA: 1 — MANE Select: NM_020137 NM_020137

CCDS: CCDS35248

Canonical transcript exons

ENST00000376423 — 26 exons

Exon	Start	End
ENSE00003006951	48998154	48998180
ENSE00003051021	48983775	48983870
ENSE00003102476	48978305	48978435
ENSE00003134631	48999238	48999299
ENSE00003201160	48990926	48991110
ENSE00003570966	48987785	48987877
ENSE00003714745	48999438	48999504
ENSE00003720900	48993428	48993578
ENSE00003724984	48981215	48981314
ENSE00003726378	48975155	48975309
ENSE00003726940	48997250	48997357
ENSE00003730580	48985268	48985402
ENSE00003732034	48981795	48981872
ENSE00003740161	48982979	48983092
ENSE00003742864	48988121	48988198
ENSE00003742967	48989972	48990003
ENSE00003744689	48990685	48990732
ENSE00003747072	48989611	48989710
ENSE00003752003	48989835	48989882
ENSE00003753049	48983228	48983440
ENSE00003990180	48976018	48976111
ENSE00003990193	48976241	48976363
ENSE00003990749	48981416	48981472
ENSE00003990770	49002188	49002264
ENSE00003990771	48981596	48981691
ENSE00003990777	48973723	48974285

Expression profiles

Bgee: expression breadth ubiquitous, 246 present calls, max score 98.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.8908 / max 157.8898, expressed in 1785 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199220	8.8915	1770
199221	1.9993	1095

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	98.59	gold quality
cerebellar hemisphere	UBERON:0002245	98.58	gold quality
cerebellar cortex	UBERON:0002129	98.54	gold quality
cerebellum	UBERON:0002037	97.96	gold quality
right frontal lobe	UBERON:0002810	96.90	gold quality
sural nerve	UBERON:0015488	96.76	gold quality
adenohypophysis	UBERON:0002196	96.43	gold quality
pituitary gland	UBERON:0000007	95.98	gold quality
anterior cingulate cortex	UBERON:0009835	95.91	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.90	gold quality
prefrontal cortex	UBERON:0000451	95.73	gold quality
granulocyte	CL:0000094	95.66	gold quality
hypothalamus	UBERON:0001898	95.57	gold quality
nucleus accumbens	UBERON:0001882	95.33	gold quality
right uterine tube	UBERON:0001302	95.24	gold quality
right lobe of thyroid gland	UBERON:0001119	95.14	gold quality
cortical plate	UBERON:0005343	94.95	gold quality
putamen	UBERON:0001874	94.91	gold quality
right ovary	UBERON:0002118	94.81	gold quality
left lobe of thyroid gland	UBERON:0001120	94.79	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.79	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.76	gold quality
left ovary	UBERON:0002119	94.68	gold quality
spleen	UBERON:0002106	94.64	gold quality
upper arm skin	UBERON:0004263	94.64	gold quality
vermiform appendix	UBERON:0001154	94.60	gold quality
frontal cortex	UBERON:0001870	94.53	gold quality
amygdala	UBERON:0001876	94.52	gold quality
neocortex	UBERON:0001950	94.52	gold quality
right adrenal gland cortex	UBERON:0035827	94.50	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.49

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 4)

• GRASP-1 was identified as an soluble autoantigen that has numerous coiled-coil domains throughout the protein. (PMID:15897011)
• Results suggest that GRASP-1 serves as a scaffold protein to facilitate MEKK-1 activation of JNK signaling in neurons. (PMID:17761173)
• We identified a new TFE3 fusion partner, GRIPAP1, in translocation renal cell carcinoma (PMID:28106924)
• results demonstrate a requirement for normal recycling endosome function in AMPAR-dependent synaptic function and neuronal connectivity in vivo, and suggest a potential role for GRASP1 in the pathophysiology of human cognitive disorders. (PMID:28285821)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gripap1	ENSDARG00000063069
mus_musculus	Gripap1	ENSMUSG00000031153
rattus_norvegicus	Gripap1	ENSRNOG00000009071

Protein

Protein identifiers

GRIP1-associated protein 1 — Q4V328 (reviewed: Q4V328)

All UniProt accessions (54): Q4V328, A0A087WT45, A0A087WW92, A0A087WWF2, A0A087WXA6, A0A994J3X9, A0A994J3Y7, A0A994J417, A0A994J436, A0A994J446, A0A994J447, A0A994J452, A0A994J461, A0A994J463, A0A994J467, A0A994J472, A0A994J484, A0A994J488, A0A994J489, A0A994J4A2, A0A994J4B5, A0A994J4D1, A0A994J4E1, A0A994J4F7, A0A994J4G1, A0A994J4H0, A0A994J4H5, A0A994J4J8, A0A994J4M4, A0A994J4N3, A0A994J4U4, A0A994J4V2, A0A994J4V9, A0A994J4W7, A0A994J4X0, A0A994J6M6, A0A994J6P1, A0A994J6Q0, A0A994J6S6, A0A994J6U0, A0A994J6U6, A0A994J6V9, A0A994J6X0, A0A994J714, A0A994J720, A0A994J724, A0A994J745, A0A994J772, A0A994J783, A0A994J790, A0A994J799, A0A994J7A3, A0A994J7B3, A0A994J7N3

UniProt curated annotations — full annotation on UniProt →

Function. Regulates the endosomal recycling back to the neuronal plasma membrane, possibly by connecting early and late recycling endosomal domains and promoting segregation of recycling endosomes from early endosomal membranes. Involved in the localization of recycling endosomes to dendritic spines, thereby playing a role in the maintenance of dendritic spine morphology. Required for the activity-induced AMPA receptor recycling to dendrite membranes and for long-term potentiation and synaptic plasticity. Functions as a scaffold protein to facilitate MAP3K1/MEKK1-mediated activation of the JNK1 kinase by phosphorylation, possibly by bringing MAP3K1/MEKK1 and JNK1 in close proximity.

Subunit / interactions. Interacts with GRIP1, GRIP2 and AMPA receptors. Interacts (via C-terminus) with MAPK8/JNK1 and MAP3K1/MEKK1; the interaction promotes MAP3K1-mediated phosphorylation of MAPK8. Interacts (via N-terminus) with RAB4A (in GTP-bound form). Interacts (via C-terminus) with STX12.

Subcellular location. Early endosome membrane. Recycling endosome membrane. Cell projection. Axon. Dendrite. Synapse.

Post-translational modifications. Proteolytically cleaved by caspase-3. A minor C-terminal proteolytic fragment of 30 kDa is produced. Proteolytic cleavage is required for JNK signaling activation.

Miscellaneous. Antibodies against GRIPAP1 have been found in sera of a patient who developed Raynaud’s syndrome and telangiectasias.

Isoforms (3)

UniProt ID	Names	Canonical?
Q4V328-1	1	yes
Q4V328-2	2
Q4V328-4	3

RefSeq proteins (1): NP_064522* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026204	GRIPAP1	Family

UniProt features (28 total): modified residue 9, splice variant 5, coiled-coil region 4, region of interest 3, chain 2, initiator methionine 1, compositionally biased region 1, site 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q4V328-F1	79.48	0.46

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 598–599 (cleavage; by caspase-3)

Post-translational modifications (9): 2, 655, 666, 668, 669, 688, 690, 691, 692

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 172 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOZGIT_ESR1_TARGETS_DN, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_SYNAPTIC_VESICLE_RECYCLING, TTGGGAG_MIR150, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_CELLULAR_LOCALIZATION, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, GOBP_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT, IRF_Q6, GOBP_ENDOCYTIC_RECYCLING

GO Biological Process (5): protein transport (GO:0015031), regulation of neurotransmitter receptor transport, endosome to postsynaptic membrane (GO:0099152), regulation of recycling endosome localization within postsynapse (GO:0099158), negative regulation of receptor clustering (GO:1903910), negative regulation of protein localization (GO:1903828)

GO Molecular Function (4): guanyl-nucleotide exchange factor activity (GO:0005085), ionotropic glutamate receptor binding (GO:0035255), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (15): nucleoplasm (GO:0005654), cytosol (GO:0005829), axon (GO:0030424), dendrite (GO:0030425), presynaptic membrane (GO:0042734), neuronal cell body (GO:0043025), recycling endosome membrane (GO:0055038), blood microparticle (GO:0072562), glutamatergic synapse (GO:0098978), extrinsic component of postsynaptic early endosome membrane (GO:0098998), endosome (GO:0005768), membrane (GO:0016020), early endosome membrane (GO:0031901), cell projection (GO:0042995), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
intracellular protein localization	2
neuron projection	2
endosome membrane	2
transport	1
establishment of protein localization	1
regulation of biological quality	1
neurotransmitter receptor transport, endosome to postsynaptic membrane	1
regulation of protein localization to synapse	1
regulation of receptor localization to synapse	1
regulation of endosome to plasma membrane protein transport	1
regulation of intracellular transport	1
synaptic vesicle recycling via endosome	1
regulation of synaptic vesicle recycling	1
receptor clustering	1
regulation of receptor clustering	1
negative regulation of protein localization to membrane	1
regulation of protein localization	1
negative regulation of biological process	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
glutamate receptor binding	1
protein binding	1
binding	1
nuclear lumen	1
cytoplasm	1
dendritic tree	1
synaptic membrane	1
presynapse	1
somatodendritic compartment	1
cell body	1
recycling endosome	1
extracellular region	1
synapse	1
postsynaptic early endosome membrane	1
extrinsic component of postsynaptic endosome membrane	1
endomembrane system	1
cytoplasmic vesicle	1
early endosome	1

Protein interactions and networks

STRING

1426 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GRIPAP1	GRIP1	Q9Y3R0	987
GRIPAP1	GRIP2	Q9C0E4	841
GRIPAP1	RAB4A	P20338	783
GRIPAP1	EEA1	Q15075	754
GRIPAP1	RALGDS	Q12967	727
GRIPAP1	RABIF	P47224	661
GRIPAP1	EXOSC2	Q13868	649
GRIPAP1	RAB11A	P24410	618
GRIPAP1	TFE3	P19532	526
GRIPAP1	MAP1B	P46821	523
GRIPAP1	BECN2	A8MW95	523
GRIPAP1	LUC7L3	O95232	505
GRIPAP1	NSG1	P42857	502
GRIPAP1	NDE1	Q9NXR1	478
GRIPAP1	MED15	Q96RN5	477

IntAct

291 interactions, top by confidence:

A	B	Type	Score
GRIPAP1	TCP10L	psi-mi:“MI:0915”(physical association)	0.740
RAB4A	GRIPAP1	psi-mi:“MI:0915”(physical association)	0.670
GRIPAP1	DNAAF19	psi-mi:“MI:0915”(physical association)	0.670
GRIPAP1	PPP1R18	psi-mi:“MI:0915”(physical association)	0.600
GRIPAP1	TEPSIN	psi-mi:“MI:0915”(physical association)	0.560
GRIPAP1	SNW1	psi-mi:“MI:0915”(physical association)	0.560
GRIPAP1	PKP2	psi-mi:“MI:0915”(physical association)	0.560
ZNF35	GRIPAP1	psi-mi:“MI:0915”(physical association)	0.560
CCNH	GRIPAP1	psi-mi:“MI:0915”(physical association)	0.560
GAS8	GRIPAP1	psi-mi:“MI:0915”(physical association)	0.560
GRIPAP1	CCDC185	psi-mi:“MI:0915”(physical association)	0.560
GRIPAP1	DUSP26	psi-mi:“MI:0915”(physical association)	0.560
HDAC4	GRIPAP1	psi-mi:“MI:0915”(physical association)	0.560
GRIPAP1	PRPF18	psi-mi:“MI:0915”(physical association)	0.560
CDC37	GRIPAP1	psi-mi:“MI:0915”(physical association)	0.560
TCEA2	GRIPAP1	psi-mi:“MI:0915”(physical association)	0.560
MFAP1	GRIPAP1	psi-mi:“MI:0915”(physical association)	0.560
TSGA10IP	GRIPAP1	psi-mi:“MI:0915”(physical association)	0.560
GRIPAP1	ZMAT2	psi-mi:“MI:0915”(physical association)	0.560
GRIPAP1	SMARCE1	psi-mi:“MI:0915”(physical association)	0.560
EHHADH	GRIPAP1	psi-mi:“MI:0915”(physical association)	0.560
TRAF2	GRIPAP1	psi-mi:“MI:0915”(physical association)	0.560
GRIPAP1	CEP57L1	psi-mi:“MI:0915”(physical association)	0.560
GRIPAP1	ING4	psi-mi:“MI:0915”(physical association)	0.560
GRIPAP1	MGC50722	psi-mi:“MI:0915”(physical association)	0.560
GRIPAP1	CBX8	psi-mi:“MI:0915”(physical association)	0.560
GRIPAP1	GRIPAP1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (226): GRIPAP1 (Biochemical Activity), GRIPAP1 (Affinity Capture-MS), GRIPAP1 (Affinity Capture-MS), GRIPAP1 (Two-hybrid), GRIPAP1 (Affinity Capture-MS), GRIPAP1 (Affinity Capture-MS), GRIPAP1 (Affinity Capture-MS), GRIPAP1 (Affinity Capture-MS), GRIPAP1 (Affinity Capture-MS), GRIPAP1 (Affinity Capture-MS), GRIPAP1 (Affinity Capture-MS), GRIPAP1 (Affinity Capture-MS), PKN3 (Affinity Capture-MS), NCKAP5L (Affinity Capture-MS), TFPT (Affinity Capture-MS)

ESM2 similar proteins: A0PJP4, A2VDP1, A5D7M3, B2RW38, D3ZUQ0, F1QNW4, O00291, O14645, O43805, O75146, O75150, O95995, Q17QG3, Q26630, Q3U319, Q499U4, Q4FZV3, Q4R3K5, Q4R7K7, Q4R7Y8, Q4V328, Q5DTM8, Q5E9C3, Q5EBL4, Q5RAU7, Q5T655, Q5VTR2, Q5ZLS3, Q60779, Q68CZ1, Q6DGZ3, Q6GN86, Q7XJ96, Q7Z3E2, Q8BKE9, Q8BR07, Q8BVN8, Q8C9S4, Q8CG73, Q8CJB9

Diamond homologs: Q4V328, Q8VD04, Q9JHZ4

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
GRIPAP1	“up-regulates activity”	MAP3K1	binding
GRIPAP1	“up-regulates activity”	MAPK8	binding
CASP3	“up-regulates activity”	GRIPAP1	cleavage
GRIP1	“up-regulates activity”	GRIPAP1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 100 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
endocytic recycling	5	14.9×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	49
Likely benign	4
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

3339 predictions. Top by Δscore:

Variant	Effect	Δscore
X:48975371:C:CT	acceptor_gain	1.0000
X:48975372:A:T	acceptor_gain	1.0000
X:48976013:CTGA:C	donor_loss	1.0000
X:48976014:TGA:T	donor_loss	1.0000
X:48976015:GAC:G	donor_loss	1.0000
X:48976016:A:AC	donor_gain	1.0000
X:48976016:A:T	donor_loss	1.0000
X:48976017:C:CC	donor_gain	1.0000
X:48976017:C:CT	donor_loss	1.0000
X:48976017:CCGAT:C	donor_gain	1.0000
X:48976204:T:TA	donor_gain	1.0000
X:48978291:T:TA	donor_gain	1.0000
X:48978299:CCTTA:C	donor_loss	1.0000
X:48978300:CTTA:C	donor_loss	1.0000
X:48978301:TTA:T	donor_loss	1.0000
X:48978302:TACC:T	donor_loss	1.0000
X:48978303:A:AC	donor_gain	1.0000
X:48978303:AC:A	donor_gain	1.0000
X:48978303:ACCCT:A	donor_loss	1.0000
X:48978304:C:CA	donor_loss	1.0000
X:48978304:C:CC	donor_gain	1.0000
X:48978304:CC:C	donor_gain	1.0000
X:48978327:T:A	donor_gain	1.0000
X:48981209:CCTCA:C	donor_loss	1.0000
X:48981210:CTCAC:C	donor_loss	1.0000
X:48981211:TCACC:T	donor_loss	1.0000
X:48981212:CAC:C	donor_loss	1.0000
X:48981213:A:AC	donor_gain	1.0000
X:48981213:A:AT	donor_loss	1.0000
X:48981214:C:A	donor_loss	1.0000

AlphaMissense

5526 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:48975180:A:G	L803P	1.000
X:48975192:A:G	L799P	1.000
X:48975204:A:G	L795P	1.000
X:48976047:A:T	I750N	1.000
X:48976068:A:G	L743P	1.000
X:48976101:A:G	L732P	1.000
X:48975173:C:A	K805N	0.999
X:48975173:C:G	K805N	0.999
X:48976035:A:T	V754D	0.999
X:48976047:A:C	I750S	0.999
X:48976050:A:T	I749N	0.999
X:48976058:C:A	K746N	0.999
X:48976058:C:G	K746N	0.999
X:48976060:T:C	K746E	0.999
X:48976251:A:G	L725P	0.999
X:48976256:C:A	W723C	0.999
X:48976256:C:G	W723C	0.999
X:48976258:A:G	W723R	0.999
X:48976258:A:T	W723R	0.999
X:48976281:A:G	L715P	0.999
X:48976284:C:G	R714P	0.999
X:48976293:A:G	L711P	0.999
X:48981250:A:G	L632P	0.999
X:48981280:C:G	R622P	0.999
X:48981292:A:G	L618P	0.999
X:48981298:C:G	R616P	0.999
X:48981304:A:G	L614P	0.999
X:48997269:A:G	L96P	0.999
X:48999488:A:G	L20P	0.999
X:48999497:A:G	L17P	0.999

dbSNP variants (sampled 300 via entrez): RS1000308434 (X:48986292 T>C), RS1000458796 (X:48976542 G>C), RS1000721860 (X:48996334 G>A), RS1001127767 (X:48999283 T>C), RS1001282072 (X:48988610 C>T), RS1001411510 (X:48978142 C>T), RS1001464019 (X:48978588 G>C), RS1001721386 (X:48998846 G>A), RS1001752818 (X:48989176 A>C), RS1002353844 (X:48991755 G>A), RS1002469718 (X:48980733 A>T), RS1003131296 (X:49003579 C>A,G,T), RS1003457083 (X:48982527 C>T), RS1003771868 (X:49003245 C>T), RS1003860380 (X:48974843 T>C)

Disease associations

OMIM: gene MIM:300408 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002382_522	Eosinophil percentage of white cells	8.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007991	eosinophil percentage of leukocytes

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

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
bisphenol A	affects cotreatment, decreases methylation, decreases expression	3
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	increases expression, affects cotreatment, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
abrine	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	decreases phosphorylation	1
Dexamethasone	affects cotreatment, decreases expression	1
Enzyme Inhibitors	increases O-linked glycosylation, decreases activity	1
Indomethacin	affects cotreatment, decreases expression	1
Ivermectin	decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Ozone	affects expression, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1
Rotenone	decreases expression	1
Valproic Acid	increases methylation	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Aflatoxin B1	decreases methylation	1
Asbestos, Crocidolite	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice