ADAP2

Summary

ADAP2 (ArfGAP with dual PH domains 2, HGNC:16487) is a protein-coding gene on chromosome 17q11.2, encoding Arf-GAP with dual PH domain-containing protein 2 (Q9NPF8). GTPase-activating protein for the ADP ribosylation factor family (Potential).

The protein encoded by this gene binds beta-tubulin and increases the stability of microtubules. The encoded protein can also translocate to the cell membrane and bind phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3) and inositol 1,3,4,5-tetrakisphosphate (InsP4). In addition, this protein is a GTPase-activating protein for ADP ribosylation factor 6 and may be able to block the entry of some RNA viruses.

Source: NCBI Gene 55803 — RefSeq curated summary.

At a glance

• GWAS associations: 18
• Clinical variants (ClinVar): 111 total — 31 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 1
• MANE Select transcript: NM_018404

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16487
Approved symbol	ADAP2
Name	ArfGAP with dual PH domains 2
Location	17q11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000184060
Ensembl biotype	protein_coding
OMIM	608635
Entrez	55803

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 20 protein_coding, 2 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000330889, ENST00000470962, ENST00000480980, ENST00000580525, ENST00000580526, ENST00000581285, ENST00000581548, ENST00000583688, ENST00000584828, ENST00000584989, ENST00000585130, ENST00000890566, ENST00000890567, ENST00000890568, ENST00000890569, ENST00000890570, ENST00000890571, ENST00000890572, ENST00000968788, ENST00000968789, ENST00000968790, ENST00000968791, ENST00000968792, ENST00000968793, ENST00000968794

RefSeq mRNA: 4 — MANE Select: NM_018404 NM_001346712, NM_001346714, NM_001346716, NM_018404

CCDS: CCDS11261, CCDS86588

Canonical transcript exons

ENST00000330889 — 11 exons

Exon	Start	End
ENSE00001295495	30926827	30926918
ENSE00001313364	30922940	30923070
ENSE00001891724	30957835	30959322
ENSE00003467930	30944907	30945053
ENSE00003470277	30954478	30954555
ENSE00003474362	30949287	30949370
ENSE00003542829	30931889	30931968
ENSE00003546319	30934185	30934297
ENSE00003638919	30953288	30953350
ENSE00003642460	30956241	30956469
ENSE00003843162	30921945	30922108

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 93.63.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.6830 / max 177.5199, expressed in 986 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
160165	2.6161	473
160164	1.0675	367
208122	1.0015	595
160166	0.5184	173
160163	0.1824	103
160162	0.1363	69
160167	0.0928	44
160161	0.0422	19
160168	0.0259	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	93.63	gold quality
mononuclear cell	CL:0000842	93.21	gold quality
leukocyte	CL:0000738	92.65	gold quality
layer of synovial tissue	UBERON:0007616	90.07	gold quality
amniotic fluid	UBERON:0000173	89.19	gold quality
granulocyte	CL:0000094	86.31	gold quality
placenta	UBERON:0001987	85.82	gold quality
spleen	UBERON:0002106	84.91	gold quality
trabecular bone tissue	UBERON:0002483	84.43	gold quality
gingival epithelium	UBERON:0001949	84.30	gold quality
blood	UBERON:0000178	84.07	gold quality
synovial joint	UBERON:0002217	83.91	gold quality
gingiva	UBERON:0001828	83.81	gold quality
vermiform appendix	UBERON:0001154	83.50	gold quality
tendon of biceps brachii	UBERON:0008188	83.29	gold quality
endothelial cell	CL:0000115	83.24	gold quality
visceral pleura	UBERON:0002401	83.24	gold quality
lower lobe of lung	UBERON:0008949	83.13	gold quality
pleura	UBERON:0000977	82.97	gold quality
gall bladder	UBERON:0002110	82.71	gold quality
parietal pleura	UBERON:0002400	82.67	gold quality
caecum	UBERON:0001153	82.66	gold quality
buccal mucosa cell	CL:0002336	82.54	silver quality
decidua	UBERON:0002450	82.46	gold quality
lymph node	UBERON:0000029	81.63	gold quality
subcutaneous adipose tissue	UBERON:0002190	81.04	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	80.93	silver quality
omental fat pad	UBERON:0010414	80.64	gold quality
peritoneum	UBERON:0002358	80.62	gold quality
pericardium	UBERON:0002407	80.35	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	41.32
E-HCAD-10	yes	39.80
E-MTAB-10287	yes	23.46
E-ANND-3	yes	21.84
E-CURD-112	yes	15.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

53 targeting ADAP2, 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-4713-3P	100.00	65.92	505
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-106A-3P	99.53	67.58	995
HSA-MIR-199A-5P	99.51	69.71	1107
HSA-MIR-199B-5P	99.51	69.74	1098
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-584-3P	99.35	67.69	1082
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-5100	99.11	67.52	1098
HSA-MIR-6506-5P	99.04	65.66	1386
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-4326	98.97	67.63	962
HSA-MIR-4709-3P	98.88	68.04	1594

Literature-anchored findings (GeneRIF, showing 5)

• The human gene for centaurin alpha 2 is located on chromosome 17, position 17q11.2, near the neurofibromatosis 1 (NF1) locus and concentrated at the plasma membrane. (PMID:14690521)
• Centaurin-alpha interacts with beta-tubulin and stabilizes microtubules. (PMID:23285209)
• Data suggest ADAP2 (an interferon-beta stimulated gene) disrupts pathogenic internalization of some RNA viruses/virions (dengue, vesicular stomatitis) by altering ADP ribosylation factor 6-mediated processes including up-regulation of pinocytosis. (PMID:26372645)
• ArfGAP domain-containing protein 2 (ADAP2) is identified as a key novel scaffolding protein that integrates different modules of the RIG-I pathway, located at distinct subcellular locations, and mediates cellular antiviral type I interferon production. (PMID:27956705)
• Elevated Expression of ADAP2 is Associated With Aggressive Behavior of Human Clear-Cell Renal Cell Carcinoma and Poor Patient Survival. (PMID:36127253)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	adap2	ENSDARG00000070565
mus_musculus	Adap2	ENSMUSG00000020709
rattus_norvegicus	Adap2	ENSRNOG00000037148

Paralogs (28): ARAP2 (ENSG00000047365), ACAP1 (ENSG00000072818), SMAP2 (ENSG00000084070), ASAP3 (ENSG00000088280), ARFGAP1 (ENSG00000101199), ADAP1 (ENSG00000105963), AGFG2 (ENSG00000106351), GIT1 (ENSG00000108262), SMAP1 (ENSG00000112305), ACAP2 (ENSG00000114331), ARAP3 (ENSG00000120318), ACAP3 (ENSG00000131584), AGAP3 (ENSG00000133612), AGAP2 (ENSG00000135439), APPL2 (ENSG00000136044), GIT2 (ENSG00000139436), ARFGAP2 (ENSG00000149182), ASAP2 (ENSG00000151693), ASAP1 (ENSG00000153317), APPL1 (ENSG00000157500), AGAP1 (ENSG00000157985), AGAP5 (ENSG00000172650), AGFG1 (ENSG00000173744), ARAP1 (ENSG00000186635), AGAP4 (ENSG00000188234), AGAP6 (ENSG00000204149), AGAP9 (ENSG00000204172), ARFGAP3 (ENSG00000242247)

Protein

Protein identifiers

Arf-GAP with dual PH domain-containing protein 2 — Q9NPF8 (reviewed: Q9NPF8)

Alternative names: Centaurin-alpha-2

All UniProt accessions (8): Q9NPF8, J3KST1, J3KT70, J3QLP8, J3QRA6, J3QRD3, K7ENT1, Q2V6Q1

UniProt curated annotations — full annotation on UniProt →

Function. GTPase-activating protein for the ADP ribosylation factor family (Potential). Binds phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3) and inositol 1,3,4,5-tetrakisphosphate (InsP4). Possesses a stoichiometry of two binding sites for InsP4 with identical affinity.

Subcellular location. Cytoplasm. Cell membrane.

Tissue specificity. Highly expressed in placenta, spleen, kidney, skeletal muscle and adrenal gland. Weakly expressed in thyroid, liver, heart, lung, small intestine, peripheral blood leukocytes. Not detected in spinal cord, brain, stomach, trachea, colon, lymph node and bone marrow.

Miscellaneous. May be due to a competing acceptor splice site.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NPF8-1	1	yes
Q9NPF8-2	2

RefSeq proteins (4): NP_001333641, NP_001333643, NP_001333645, NP_060874* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001164	ArfGAP_dom	Domain
IPR001849	PH_domain	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR037278	ARFGAP/RecO	Homologous_superfamily
IPR037849	PH1_ADAP	Domain
IPR037851	PH2_ADAP	Domain
IPR038508	ArfGAP_dom_sf	Homologous_superfamily
IPR052589	Arf-GAP_dual-PH_domain	Family

Pfam: PF00169, PF01412

UniProt features (7 total): domain 3, chain 1, zinc finger region 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NPF8-F1	92.49	0.84

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 243 (showing top): TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, BENPORATH_ES_WITH_H3K27ME3, PEREZ_TP63_TARGETS, chr17q11, FOSTER_TOLERANT_MACROPHAGE_UP, LU_TUMOR_VASCULATURE_UP, GOCC_MITOCHONDRIAL_ENVELOPE, TGANTCA_AP1_C, PEREZ_TP53_AND_TP63_TARGETS, GOBP_CIRCULATORY_SYSTEM_DEVELOPMENT, LU_TUMOR_ENDOTHELIAL_MARKERS_UP, STAT1_02, DIAZ_CHRONIC_MYELOGENOUS_LEUKEMIA_DN, GOMF_PHOSPHATIDYLINOSITOL_4_5_BISPHOSPHATE_BINDING, GOMF_PHOSPHATIDYLINOSITOL_PHOSPHATE_BINDING

GO Biological Process (2): heart development (GO:0007507), positive regulation of GTPase activity (GO:0043547)

GO Molecular Function (10): GTPase activator activity (GO:0005096), phosphatidylinositol-4,5-bisphosphate binding (GO:0005546), phosphatidylinositol-3,4,5-trisphosphate binding (GO:0005547), zinc ion binding (GO:0008270), protein-macromolecule adaptor activity (GO:0030674), phosphatidylinositol-3,4-bisphosphate binding (GO:0043325), inositol 1,3,4,5 tetrakisphosphate binding (GO:0043533), protein binding (GO:0005515), metal ion binding (GO:0046872), phosphatidylinositol bisphosphate binding (GO:1902936)

GO Cellular Component (4): cytoplasm (GO:0005737), mitochondrial envelope (GO:0005740), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
anion binding	3
GTPase activity	2
phosphatidylinositol phosphate binding	2
phosphatidylinositol bisphosphate binding	2
cellular anatomical structure	2
animal organ development	1
circulatory system development	1
regulation of GTPase activity	1
positive regulation of hydrolase activity	1
enzyme activator activity	1
GTPase regulator activity	1
transition metal ion binding	1
protein binding	1
molecular adaptor activity	1
alcohol binding	1
binding	1
cation binding	1
intracellular anatomical structure	1
mitochondrion	1
organelle envelope	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1030 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADAP2	RNF135	Q8IUD6	779
ADAP2	EVI2A	P22794	765
ADAP2	EVI2B	P34910	742
ADAP2	NF1	P21359	714
ADAP2	UTP6	Q9NYH9	708
ADAP2	CRLF3	Q8IUI8	707
ADAP2	LRRC37B	Q96QE4	691
ADAP2	SUZ12	Q15022	674
ADAP2	TEFM	Q96QE5	646
ADAP2	COPRS	Q9NQ92	636
ADAP2	RAB11FIP4	Q86YS3	632
ADAP2	ATAD5	Q96QE3	626
ADAP2	PLEK2	Q9NYT0	564
ADAP2	PLEK	P08567	563
ADAP2	CDK5R1	Q15078	496

IntAct

7 interactions, top by confidence:

A	B	Type	Score
ADAP2	KCTD10	psi-mi:“MI:0915”(physical association)	0.400
MICA	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350
PRNP	ADAP2	psi-mi:“MI:0407”(direct interaction)	0.000
IKBKG	ADAP2	psi-mi:“MI:0407”(direct interaction)	0.000
ADAP2	EEF1G	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (21): KCTD10 (Affinity Capture-MS), ADAP2 (Affinity Capture-MS), ADAP2 (Affinity Capture-MS), KCTD10 (Affinity Capture-MS), ADAP2 (Affinity Capture-RNA), TUBB (Two-hybrid), TUBB (Affinity Capture-Western), EEF1G (Two-hybrid), KCTD10 (Affinity Capture-MS), ADAP2 (Affinity Capture-MS), ADAP2 (Affinity Capture-MS), ADAP2 (Cross-Linking-MS (XL-MS)), ADAP2 (Reconstituted Complex), ADAP2 (Reconstituted Complex), ADAP2 (Biochemical Activity)

ESM2 similar proteins: O00170, O08915, O75689, O97627, O97628, P08487, P08567, P10686, P16885, P19174, P21146, P24135, P25098, P26817, P26818, P26819, P34512, P35626, P41229, P49619, P49620, P70392, Q09639, Q22070, Q24145, Q38JA7, Q3UYH7, Q4KM33, Q4PMC9, Q5F3R2, Q5FWY5, Q62077, Q64682, Q6IQX0, Q6Q308, Q7YRC1, Q8CIG3, Q8CIH5, Q8NB78, Q8R2V5

Diamond homologs: A1L520, A1Z7A6, A5PK26, A6NIR3, O43150, O74345, O75689, O80925, O82171, O94601, O97902, P35197, P38682, P40529, P52594, Q04412, Q09531, Q0WQQ1, Q10165, Q10367, Q14161, Q15027, Q15057, Q17R07, Q1AAU6, Q1ZXH8, Q28CM8, Q2TA45, Q3MID3, Q3UHD9, Q4KLH5, Q4KLN7, Q4LDD4, Q4R4C9, Q5F413, Q5FVC7, Q5R787, Q5RAT7, Q5U464, Q5VTM2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	31
Likely pathogenic	4
Uncertain significance	65
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1172820	Single allele	Pathogenic
150276	GRCh38/hg38 17q11.2(chr17:30706845-31999933)x1	Pathogenic
151510	GRCh38/hg38 17q11.2(chr17:30684919-32021402)x1	Pathogenic
153222	GRCh38/hg38 17q11.2(chr17:30666018-32085769)x1	Pathogenic
153736	GRCh38/hg38 17q11.2(chr17:30625268-32059496)x1	Pathogenic
155211	GRCh38/hg38 17q11.2(chr17:30678153-32073866)x1	Pathogenic
160878	GRCh38/hg38 17q11.2(chr17:30706864-31999939)x1	Pathogenic
1678524	NC_000017.11:g.30660608_31159168inv	Pathogenic
1703547	GRCh37/hg19 17q11.2(chr17:28993036-30412788)	Pathogenic
1710521	GRCh37/hg19 17q11.2(chr17:29076232-30043725)x1	Pathogenic
2671621	Single allele	Pathogenic
2685600	GRCh37/hg19 17q11.2(chr17:28387597-30812008)x1	Pathogenic
3063487	GRCh37/hg19 17q11.2(chr17:28277040-30903559)x1	Pathogenic
3242851	NC_000017.10:g.(?28524804)(29624377_?)del	Pathogenic
394485	GRCh37/hg19 17q11.2(chr17:28959760-30367155)x1	Pathogenic
441568	GRCh37/hg19 17q11.2(chr17:28997791-30386515)x1	Pathogenic
442660	GRCh37/hg19 17q11.2(chr17:28993036-30386515)x1	Pathogenic
443291	GRCh37/hg19 17q11.2(chr17:29103348-30298773)x1	Pathogenic
4820058	NC_000017.11:g.(30668200_30669500)_(32083800_32085200)del	Pathogenic
564425	GRCh37/hg19 17q11.2(chr17:28997893-30391813)x1	Pathogenic
58136	GRCh38/hg38 17q11.2(chr17:30630734-32088380)x3	Pathogenic
60460	GRCh38/hg38 17q11.2(chr17:30672816-31999939)x1	Pathogenic
60461	GRCh38/hg38 17q11.2(chr17:30706863-31994624)x1	Pathogenic
60462	GRCh38/hg38 17q11.2(chr17:30767194-31937486)x1	Pathogenic
625731	GRCh37/hg19 17q11.2(chr17:29111368-30183819)	Pathogenic
666441	GRCh37/hg19 17q11.2(chr17:28941066-30326958)x1	Pathogenic
685655	GRCh37/hg19 17q11.2(chr17:28999903-30409337)x1	Pathogenic
687019	GRCh37/hg19 17q11.2(chr17:29054315-30409336)x1	Pathogenic
688115	GRCh37/hg19 17q11.2(chr17:29054315-30391711)x3	Pathogenic
815923	GRCh37/hg19 17q11.2(chr17:29088218-30159137)x1	Pathogenic

SpliceAI

1976 predictions. Top by Δscore:

Variant	Effect	Δscore
17:30923068:G:GT	donor_gain	1.0000
17:30923113:G:GT	donor_gain	1.0000
17:30926915:GCCT:G	donor_gain	1.0000
17:30926919:G:GG	donor_gain	1.0000
17:30931884:TTTA:T	acceptor_loss	1.0000
17:30931885:TTA:T	acceptor_loss	1.0000
17:30931886:TA:T	acceptor_loss	1.0000
17:30931887:A:AG	acceptor_gain	1.0000
17:30931887:AG:A	acceptor_gain	1.0000
17:30931888:G:GG	acceptor_gain	1.0000
17:30931888:GG:G	acceptor_gain	1.0000
17:30931964:CCCAG:C	donor_loss	1.0000
17:30931965:CCAG:C	donor_loss	1.0000
17:30931966:CAGG:C	donor_loss	1.0000
17:30931967:AGGTA:A	donor_loss	1.0000
17:30931968:GGTAA:G	donor_loss	1.0000
17:30931970:T:G	donor_loss	1.0000
17:30934174:T:TA	acceptor_gain	1.0000
17:30934177:T:TA	acceptor_gain	1.0000
17:30934181:TAA:T	acceptor_loss	1.0000
17:30934183:AGG:A	acceptor_loss	1.0000
17:30934184:G:GT	acceptor_loss	1.0000
17:30934294:ACAGG:A	donor_loss	1.0000
17:30934298:GTA:G	donor_loss	1.0000
17:30934299:T:A	donor_loss	1.0000
17:30944905:AG:A	acceptor_gain	1.0000
17:30944906:GG:G	acceptor_gain	1.0000
17:30954476:A:AG	acceptor_gain	1.0000
17:30954477:G:GG	acceptor_gain	1.0000
17:30954553:CTGGT:C	donor_loss	1.0000

AlphaMissense

2507 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:30944989:T:C	L198P	0.998
17:30956412:T:A	W352R	0.997
17:30956412:T:C	W352R	0.997
17:30923050:T:A	W69R	0.996
17:30923050:T:C	W69R	0.996
17:30922978:T:C	C45R	0.995
17:30923003:G:C	R53P	0.995
17:30931905:T:A	W112R	0.995
17:30931905:T:C	W112R	0.995
17:30931919:G:C	K116N	0.995
17:30931919:G:T	K116N	0.995
17:30934210:G:C	K141N	0.995
17:30934210:G:T	K141N	0.995
17:30954501:G:C	R276S	0.995
17:30954501:G:T	R276S	0.995
17:30931914:G:C	A115P	0.994
17:30953338:G:C	K264N	0.994
17:30953338:G:T	K264N	0.994
17:30922948:T:A	W35R	0.993
17:30922948:T:C	W35R	0.993
17:30922980:T:G	C45W	0.993
17:30923052:G:C	W69C	0.993
17:30923052:G:T	W69C	0.993
17:30931935:T:C	F122L	0.993
17:30931937:T:A	F122L	0.993
17:30931937:T:G	F122L	0.993
17:30934280:T:C	Y165H	0.993
17:30949299:T:A	W224R	0.993
17:30949299:T:C	W224R	0.993
17:30954500:G:C	R276T	0.993

dbSNP variants (sampled 300 via entrez): RS1000095516 (17:30941888 A>G), RS1000180252 (17:30925021 C>G,T), RS1000319106 (17:30954890 C>T), RS1000520306 (17:30956848 C>T), RS1000665753 (17:30948269 T>C), RS1000787875 (17:30929443 C>T), RS1000915457 (17:30936649 G>A,C), RS1000975929 (17:30956632 T>C), RS1001002633 (17:30936634 T>G), RS1001212943 (17:30932334 A>T), RS1001223133 (17:30958642 C>T), RS1001388297 (17:30920481 C>A,T), RS1001419540 (17:30925860 A>G), RS1001495472 (17:30927158 T>C), RS1001592305 (17:30958355 G>A)

Disease associations

OMIM: gene MIM:608635 | disease phenotypes: MIM:162200, MIM:613675, MIM:618786

GenCC curated gene-disease

Mondo (4): cerebral palsy (MONDO:0006497), neurofibromatosis type 1 (MONDO:0018975), chromosome 17q11.2 deletion syndrome, 1.4Mb (MONDO:0013357), Imagawa-Matsumoto syndrome (MONDO:0032916)

Orphanet (5): Neurofibromatosis type 1 (Orphanet:636), 17q11.2 microduplication syndrome (Orphanet:139474), 17q11 microdeletion syndrome (Orphanet:97685), Imagawa-Matsumoto syndrome (Orphanet:659463), Overgrowth-macrocephaly-facial dysmorphism syndrome (Orphanet:137634)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0100021	Cerebral palsy

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST000175_4	Height	2.000000e-09
GCST002647_120	Height	3.000000e-41
GCST004063_114	Waist circumference adjusted for body mass index	8.000000e-08
GCST004063_163	Waist circumference adjusted for body mass index	9.000000e-10
GCST004500_3	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	1.000000e-07
GCST004500_45	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	7.000000e-08
GCST004501_13	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	6.000000e-07
GCST004501_14	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	7.000000e-07
GCST004504_34	Waist circumference adjusted for BMI in non-smokers	7.000000e-07
GCST004504_35	Waist circumference adjusted for BMI in non-smokers	4.000000e-06
GCST004602_291	Mean corpuscular volume	1.000000e-19
GCST004630_213	Mean corpuscular hemoglobin	1.000000e-18
GCST008163_513	Height	9.000000e-15
GCST012226_793	Waist circumference adjusted for body mass index	1.000000e-17
GCST012227_335	Hip circumference adjusted for BMI	6.000000e-22
GCST90002392_13	Mean corpuscular volume	2.000000e-43
GCST90002396_615	Mean reticulocyte volume	3.000000e-22
GCST90002397_740	Mean spheric corpuscular volume	3.000000e-29

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007789	BMI-adjusted waist circumference
EFO:0004318	smoking behavior
EFO:0004527	mean corpuscular hemoglobin
EFO:0008039	BMI-adjusted hip circumference
EFO:0010701	mean reticulocyte volume

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D002547	Cerebral Palsy	C10.228.140.140.254
D009456	Neurofibromatosis 1	C04.557.580.600.580.590.650; C04.700.631.650; C10.562.600.500; C10.574.500.549.400; C10.668.829.675; C16.320.400.560.400; C16.320.700.633.650
C563524	NF1 Microdeletion Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	3
Arsenic	decreases expression, increases abundance	2
Benzo(a)pyrene	decreases expression, decreases methylation	2
Nickel	increases expression	2
2,4,6-tribromophenol	decreases expression	1
propionaldehyde	increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	decreases expression	1
sodium arsenate	decreases expression, increases abundance	1
decabromobiphenyl ether	decreases expression	1
sodium arsenite	increases expression	1
tetrabromobisphenol A	decreases expression	1
hydroquinone	increases expression	1
pentanal	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Estradiol	affects cotreatment, increases expression	1
Progesterone	affects cotreatment, increases expression	1
Sodium Dodecyl Sulfate	decreases expression	1
Taurine	increases expression	1
Tretinoin	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cyclosporine	increases expression	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00154830	PHASE4	COMPLETED	Alterations of Functional Activities and Leg Stiffness After Hamstring Lengthening in Cerebral Palsy Children
NCT00432055	PHASE4	COMPLETED	Effects of Botulinum Toxin Type A in Adults With Cerebral Palsy
NCT00549471	PHASE4	TERMINATED	Improvement After Botulinum Toxin Injections to the Arms in Children With Cerebral Palsy
NCT00752934	PHASE4	TERMINATED	Does Oral Baclofen Improve Care and Comfort in Spastic Children in Nursing Homes?
NCT00964639	PHASE4	COMPLETED	Postoperative Pain in Children With Cerebral Palsy After Pelvic and Femoral Osteotomies
NCT01386255	PHASE4	WITHDRAWN	Placebo Controlled Study of Baclofen for GERD in Children With Cerebral Palsy
NCT02546999	PHASE4	COMPLETED	Does Botulinum Toxin A Make Walking Easier in Children With Cerebral Palsy?
NCT02633241	PHASE4	COMPLETED	A Pilot Study of Dexmedetomidine-Propofol in Children Undergoing Magnetic Resonance Imaging
NCT03117322	PHASE4	COMPLETED	Synbiotic, Prebiotics and Probiotics in Children With Cerebral Palsy and Constipation
NCT03648658	PHASE4	UNKNOWN	Paracetamol Study in Patients With Low Muscle Mass
NCT04074265	PHASE4	COMPLETED	Peri-operative Use of a Pain Injection in Pediatric Patients With Cerebral Palsy
NCT04273737	PHASE4	TERMINATED	Amantadine in Treating Cognitive & Motor Impairments in Adolescents and Adults With Cerebral Palsy
NCT04523935	PHASE4	COMPLETED	Excessive Crying in Children With Cerebral Palsy and Communication Deficits
NCT05887765	PHASE4	COMPLETED	Effect of Systematic Dexamethasone on the Duration of Popliteal Nerve Block for Anesthesia After Pediatric Ankle Surgery
NCT06176430	PHASE4	UNKNOWN	Comparison of Twice Weekly Versus Daily Iron Therapy in Treating Anemia in Children With Cerebral Palsy
NCT06189781	PHASE4	RECRUITING	Pain Injection Versus Epidural Anesthesia for Hip Surgery in Pediatric Patients With Cerebral Palsy
NCT00014989	PHASE3	COMPLETED	Beneficial Effects of Antenatal Magnesium Sulfate (BEAM Trial)
NCT00065949	PHASE3	UNKNOWN	Magnesium Sulfate to Prevent Brain Injury in Premature Infants
NCT00367068	PHASE3	COMPLETED	Dutch National ITB Study in Children With Cerebral Palsy
NCT00491894	PHASE3	COMPLETED	Safety and Efficacy Study of Oral Glycopyrrolate Liquid for the Treatment of Pathologic (Chronic Moderate to Severe) Drooling in Pediatric Patients 3 to 18 Years of Age With Cerebral Palsy or Other Neurologic Conditions
NCT00632528	PHASE3	COMPLETED	MEOPA to Improve Physical Therapy Results After Multilevel Surgery
NCT00822029	PHASE3	TERMINATED	Use of Oral Bisphosphonates in the Treatment of Osteoporosis of Non-walking Children With Cerebral Palsy
NCT00922077	PHASE3	COMPLETED	Individualized Neurodevelopmental Treatment
NCT01249417	PHASE3	COMPLETED	Dysport® Pediatric Lower Limb Spasticity Study
NCT01251380	PHASE3	COMPLETED	Dysport® Pediatric Lower Limb Spasticity Follow-on Study
NCT01437644	PHASE3	COMPLETED	The Post-Operative Pain in Cerebral Palsy (POPPIES) Trial
NCT01492608	PHASE3	COMPLETED	Magnesium Sulphate for Preterm Birth (MASP Study)
NCT01603602	PHASE3	COMPLETED	BOTOX® Treatment in Pediatric Upper Limb Spasticity
NCT01603615	PHASE3	COMPLETED	BOTOX® Open-Label Treatment in Pediatric Upper Limb Spasticity
NCT01603628	PHASE3	COMPLETED	BOTOX® Treatment in Pediatric Lower Limb Spasticity
NCT01603641	PHASE3	COMPLETED	BOTOX® Open-Label Treatment in Pediatric Lower Limb Spasticity
NCT01633736	PHASE3	UNKNOWN	Targeted Hip Strength Training in Children With Cerebral Palsy (CP)
NCT01898520	PHASE3	COMPLETED	A Safety, Efficacy and Tolerability Study of Sativex for the Treatment of Spasticity in Children Aged 8 to 18 Years
NCT01929434	PHASE3	COMPLETED	Efficacy of Stem Cell Transplantation Compared to Rehabilitation Treatment of Patients With Cerebral Paralysis
NCT02002884	PHASE3	COMPLETED	Dose-response Study of Efficacy and Safety of Botulinum Toxin Type A to Treat Spasticity of the Arm(s) or of Arm(s) and Leg(s) in Cerebral Palsy
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02839785	PHASE3	TERMINATED	Analgesia and Physiotherapy in Children With Cerebral Palsy (ANTALKINECP)
NCT03110341	PHASE3	UNKNOWN	Effect of Erythropoietin in Premature Infants on White Matter Lesions and Neurodevelopmental Outcome
NCT03302871	PHASE3	COMPLETED	Integrated Management Enhances Functional Gains in Children With Cerebral Palsy Treated by BoNT-A
NCT03306212	PHASE3	COMPLETED	Efficacy of Intermittent Serial Casting on Spastic Wrist Flexion Deformity