SRPX2

Summary

SRPX2 (sushi repeat containing protein X-linked 2, HGNC:30668) is a protein-coding gene on chromosome Xq22.1, encoding Sushi repeat-containing protein SRPX2 (O60687). Acts as a ligand for the urokinase plasminogen activator surface receptor.

This gene encodes a secreted protein that contains three sushi repeat motifs. The encoded protein may play a role in the development of speech and language centers in the brain. This protein may also be involved in angiogenesis. Mutations in this gene are the cause of bilateral perisylvian polymicrogyria, rolandic epilepsy, speech dyspraxia and cognitive disability.

Source: NCBI Gene 27286 — RefSeq curated summary.

At a glance

• Gene–disease (curated): rolandic epilepsy-speech dyspraxia syndrome (Supportive, GenCC) — +3 more curated relationships
• Clinical variants (ClinVar): 244 total — 2 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 78
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_014467

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30668
Approved symbol	SRPX2
Name	sushi repeat containing protein X-linked 2
Location	Xq22.1
Locus type	gene with protein product
Status	Approved
Aliases	SRPUL
Ensembl gene	ENSG00000102359
Ensembl biotype	protein_coding
OMIM	300642
Entrez	27286

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 5 protein_coding_CDS_not_defined, 4 protein_coding, 2 retained_intron

ENST00000373004, ENST00000481988, ENST00000638319, ENST00000638458, ENST00000638738, ENST00000638920, ENST00000640020, ENST00000640282, ENST00000640889, ENST00000677630, ENST00000679590

RefSeq mRNA: 1 — MANE Select: NM_014467 NM_014467

CCDS: CCDS14471

Canonical transcript exons

ENST00000373004 — 11 exons

Exon	Start	End
ENSE00000673413	100650785	100650865
ENSE00000673414	100662176	100662367
ENSE00000673417	100664774	100664950
ENSE00000673433	100665243	100665369
ENSE00000673454	100665536	100665657
ENSE00000673471	100666754	100666933
ENSE00000673474	100667274	100667407
ENSE00000673475	100669248	100669369
ENSE00001459307	100646193	100646404
ENSE00002606678	100670807	100675788
ENSE00003807114	100644199	100644515

Expression profiles

Bgee: expression breadth ubiquitous, 211 present calls, max score 97.55.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.1725 / max 1681.0491, expressed in 1154 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196933	18.8228	1121
196936	2.6981	511
196934	0.5256	313
209757	0.1260	52

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	97.55	gold quality
calcaneal tendon	UBERON:0003701	95.68	gold quality
cartilage tissue	UBERON:0002418	95.24	gold quality
lower esophagus mucosa	UBERON:0035834	94.96	gold quality
omental fat pad	UBERON:0010414	93.41	gold quality
peritoneum	UBERON:0002358	93.33	gold quality
tendon	UBERON:0000043	92.98	gold quality
adipose tissue of abdominal region	UBERON:0007808	92.95	gold quality
sural nerve	UBERON:0015488	92.50	gold quality
tendon of biceps brachii	UBERON:0008188	92.27	gold quality
subcutaneous adipose tissue	UBERON:0002190	91.53	gold quality
adipose tissue	UBERON:0001013	90.93	gold quality
connective tissue	UBERON:0002384	90.52	gold quality
tibial nerve	UBERON:0001323	90.33	gold quality
esophagus mucosa	UBERON:0002469	90.27	gold quality
right lung	UBERON:0002167	89.68	gold quality
left ovary	UBERON:0002119	89.25	gold quality
pericardium	UBERON:0002407	89.08	gold quality
right ovary	UBERON:0002118	89.05	gold quality
left coronary artery	UBERON:0001626	88.69	gold quality
metanephros cortex	UBERON:0010533	87.95	gold quality
ascending aorta	UBERON:0001496	87.89	gold quality
thoracic aorta	UBERON:0001515	87.71	gold quality
coronary artery	UBERON:0001621	87.18	gold quality
tibia	UBERON:0000979	87.10	gold quality
descending thoracic aorta	UBERON:0002345	86.81	gold quality
esophagus	UBERON:0001043	86.76	gold quality
amniotic fluid	UBERON:0000173	86.47	gold quality
apex of heart	UBERON:0002098	86.47	gold quality
esophagus squamous epithelium	UBERON:0006920	86.35	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	26.92
E-MTAB-5061	yes	11.39

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXP2

miRNA regulators (miRDB)

34 targeting SRPX2, 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-3162-3P	100.00	65.37	363
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-548U	99.65	67.78	1463
HSA-MIR-651-5P	99.64	68.49	1104
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-10524-5P	99.05	66.08	963
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-6749-3P	99.00	65.73	1443
HSA-MIR-4680-3P	98.64	68.60	2093
HSA-MIR-4780	98.57	64.75	611
HSA-MIR-4691-5P	98.41	66.77	1343
HSA-MIR-6792-3P	98.41	66.86	1359
HSA-MIR-660-3P	98.14	66.04	1434
HSA-MIR-1910-5P	97.42	66.36	844
HSA-MIR-6748-3P	97.20	65.66	836

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 22)

• The involvement of SRPX2 in these disorders suggests an important role for SRPX2 in the perisylvian region critical for language and cognitive development. (PMID:16497722)
• The R75K human-specific variation occurred in an important functional loop of the first sushi domain of SRPX2, indicating that this evolutionary mutation may have functional importance (PMID:17942002)
• Interaction of SRPX2 with uPAR involved in the functioning, the development and disorders of the speech cortex. (PMID:18718938)
• the biological functions of SRPX2 include cellular migration and adhesion to cancer cells. (PMID:19065654)
• These findings suggest that Srpx2 regulates endothelial cell migration and tube formation and provides a new target for modulating angiogenesis. (PMID:19667118)
• acts as regulator of ICAM1 and E-selectin during endotoxemia (PMID:20236627)
• The FOXP2-SRPX2/uPAR network provides exciting insights into molecular pathways underlying speech-related disorders. (PMID:20858596)
• The SRPX2 protein contains the P-DUDES structural domain in its C-terminal region. This domain has significant albeit remote sequence similarity to thioredoxin-like domains, and is predicted to possess an oxidoreductase function. (PMID:209648)
• SRPX2 is a novel chondroitin sulfate proteoglycan that is overexpressed in gastrointestinal cancer cells. (PMID:22242148)
• Hypomethylation of SRPX2 appeared at the transition from adenoma to carcinoma, and was correlated with adenocarcinoma histology, microsatellite stability, and poor differentiation. (PMID:23115050)
• SRPX2 is an epilepsy- and language-associated gene that is a target of the foxhead box protein P2 (FoxP2) transcription factor. (PMID:24179158)
• High SRPX2 expression is associated with gastric cancer. (PMID:24700475)
• In rolandic epilepsy patients no major role was found for an association with SRPX2 or ELP4 genes. (PMID:24995671)
• Increased Sushi repeat-containing protein X-linked 2 is associated with progression of colorectal cancer. (PMID:25737434)
• SRPX2 potentially acts as an independent prognostic predictor and a drug-target for hepatocellular carcinoma patients. (PMID:28654796)
• This study suggests that SRPX2 promotes angiogenesis of HUVECs through the cooperation of the uPAR and integrin/FAK pathway. (PMID:28867754)
• We explore the contribution of SRPX2 variants to clinical phenotype in our patients and conclude that these variants at least partially explain the phenotype. Further studies are necessary to establish and confirm the association between SRPX2 and neurodevelopment particularly speech and language development. (PMID:30393191)
• Knockdown of SRPX2 inhibits cell proliferation and metastasis, and promotes chemosensitivity in esophageal squamous cell carcinoma cells. (PMID:30551519)
• Sushi Repeat Containing Protein X-linked 2 Is a Downstream Signal of LEM Domain Containing 1 and Acts as a Tumor-Promoting Factor in Oral Squamous Cell Carcinoma. (PMID:32455867)
• SRPX2 promotes cell proliferation and invasion via activating FAK/SRC/ERK pathway in non-small cell lung cancer. (PMID:32550700)
• Local administration of liposomal-based Srpx2 gene therapy reverses pulmonary fibrosis by blockading fibroblast-to-myofibroblast transition. (PMID:34093874)
• SRPX2 promotes cancer cell proliferation and migration of papillary thyroid cancer. (PMID:37306872)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	srpx2	ENSDARG00000034559
mus_musculus	Srpx2	ENSMUSG00000031253
rattus_norvegicus	Srpx2	ENSRNOG00000003715

Paralogs (39): CFH (ENSG00000000971), SELE (ENSG00000007908), C8B (ENSG00000021852), C6 (ENSG00000039537), SEZ6 (ENSG00000063015), CFHR2 (ENSG00000080910), APOH (ENSG00000091583), SEZ6L (ENSG00000100095), SUSD6 (ENSG00000100647), SRPX (ENSG00000101955), C7 (ENSG00000112936), C9 (ENSG00000113600), PAPPA2 (ENSG00000116183), CFHR3 (ENSG00000116785), CR2 (ENSG00000117322), CD46 (ENSG00000117335), CSMD2 (ENSG00000121904), C4BPA (ENSG00000123838), C4BPB (ENSG00000123843), CFHR4 (ENSG00000134365), CFHR5 (ENSG00000134389), F13B (ENSG00000143278), SUSD4 (ENSG00000143502), C8A (ENSG00000157131), SUSD3 (ENSG00000157303), CSMD3 (ENSG00000164796), SVEP1 (ENSG00000165124), C2 (ENSG00000166278), SELP (ENSG00000174175), SEZ6L2 (ENSG00000174938), PRF1 (ENSG00000180644), PAPPA (ENSG00000182752), CSMD1 (ENSG00000183117), SELL (ENSG00000188404), CD55 (ENSG00000196352), CR1L (ENSG00000197721), CR1 (ENSG00000203710), CFB (ENSG00000243649), CFHR1 (ENSG00000244414)

Protein

Protein identifiers

Sushi repeat-containing protein SRPX2 — O60687 (reviewed: O60687)

Alternative names: Sushi-repeat protein upregulated in leukemia

All UniProt accessions (4): O60687, A0A1W2PNZ6, A0A1W2PR88, A0A1W2PRB1

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a ligand for the urokinase plasminogen activator surface receptor. Plays a role in angiogenesis by inducing endothelial cell migration and the formation of vascular network (cords). Involved in cellular migration and adhesion. Increases the phosphorylation levels of FAK. Interacts with and increases the mitogenic activity of HGF. Promotes synapse formation. May have a role in the perisylvian region, critical for language and cognitive development.

Subunit / interactions. Forms homooligomers. Interacts with PLAUR (via the UPAR/Ly6 domains), ADAMTS4 and CTSB. Interacts with HGF; the interaction increases the mitogenic activity of HGF.

Subcellular location. Secreted. Cytoplasm. Cell surface. Synapse.

Tissue specificity. Expressed in neurons of the rolandic area of the brain (at protein level). Highly expressed in the brain, placenta, lung, trachea, uterus, adrenal gland, heart, ovary and placenta. Weakly expressed in the peripheral blood, brain and bone marrow. Expressed in numerous cancer cell lines and in gastrointestinal cancer cells. Higher levels found in colorectal cancers than in normal colonic mucosa.

Post-translational modifications. Contains chondroitin sulfate chains.

Disease relevance. Rolandic epilepsy, impaired intellectual development, and speech dyspraxia, X-linked (RESDX) [MIM:300643] A condition characterized by the association of rolandic seizures with oral and speech dyspraxia, and intellectual disability. Rolandic seizures occur during a period of significant brain maturation. During this time, dysfunction of neural network activities such as focal discharges may be associated with specific developmental disabilities resulting in specific cognitive impairments of language, visuo-spatial abilities or attention. The disease may be caused by variants affecting the gene represented in this entry.

RefSeq proteins (1): NP_055282* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000436	Sushi_SCR_CCP_dom	Domain
IPR003410	HYR_dom	Domain
IPR025232	DUF4174	Domain
IPR035976	Sushi/SCR/CCP_sf	Homologous_superfamily
IPR043555	SRPX-like	Family

Pfam: PF00084, PF02494, PF13778

UniProt features (15 total): disulfide bond 6, domain 4, sequence variant 3, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60687-F1	86.75	0.76

Functional residue map

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

Disulfide bonds (6): 264–306, 292–319, 71–105, 91–117, 122–163, 149–176

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 338 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GSE45365_NK_CELL_VS_CD8A_DC_UP, GOBP_BEHAVIOR, GOBP_REGULATION_OF_PHOSPHORYLATION, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GOBP_SYNAPSE_ASSEMBLY, GOBP_POSITIVE_REGULATION_OF_SYNAPSE_ASSEMBLY, GOBP_CELL_MIGRATION_INVOLVED_IN_SPROUTING_ANGIOGENESIS, GOCC_CELL_SURFACE, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, TAL1ALPHAE47_01, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_POSITIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_ENDOTHELIAL_CELL_MIGRATION

GO Biological Process (9): angiogenesis (GO:0001525), regulation of phosphorylation (GO:0042325), cell motility (GO:0048870), positive regulation of synapse assembly (GO:0051965), vocalization behavior (GO:0071625), positive regulation of cell migration involved in sprouting angiogenesis (GO:0090050), cell-cell adhesion (GO:0098609), cell adhesion (GO:0007155), regulation of synapse assembly (GO:0051963)

GO Molecular Function (5): signaling receptor binding (GO:0005102), hepatocyte growth factor binding (GO:0036458), identical protein binding (GO:0042802), extracellular matrix structural constituent (GO:0005201), protein binding (GO:0005515)

GO Cellular Component (9): obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), cell surface (GO:0009986), extracellular matrix (GO:0031012), excitatory synapse (GO:0060076), synaptic membrane (GO:0097060), glutamatergic synapse (GO:0098978), extracellular region (GO:0005576), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
synapse	3
cellular process	2
synapse assembly	2
protein binding	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
phosphorylation	1
regulation of metabolic process	1
positive regulation of nervous system development	1
regulation of synapse assembly	1
positive regulation of cell junction assembly	1
behavior	1
cell migration involved in sprouting angiogenesis	1
positive regulation of blood vessel endothelial cell migration	1
regulation of cell migration involved in sprouting angiogenesis	1
cell adhesion	1
regulation of synapse organization	1
regulation of cell junction assembly	1
growth factor binding	1
structural molecule activity	1
extracellular matrix	1
binding	1
intracellular anatomical structure	1
external encapsulating structure	1
plasma membrane region	1
cell junction	1

Protein interactions and networks

STRING

942 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SRPX2	PLAUR	Q03405	877
SRPX2	A0A087WTN9	A0A087WTN9	827
SRPX2	HLF	Q16534	760
SRPX2	PLAU	P00749	712
SRPX2	TCF3	P15883	706
SRPX2	ADAMTS4	O75173	700
SRPX2	TLE6	Q9H808	668
SRPX2	TLE2	Q04725	667
SRPX2	DBP	Q10586	640
SRPX2	CALM1	P02593	636
SRPX2	CX3CL1	P78423	595
SRPX2	TFPT	P0C1Z6	590
SRPX2	PVALB	P20472	583
SRPX2	CALB2	P22676	578
SRPX2	TEF	Q10587	549
SRPX2	IL3	P08700	549

IntAct

12 interactions, top by confidence:

A	B	Type	Score
C1QTNF9	C1QTNF9B	psi-mi:“MI:0914”(association)	0.780
NOTCH2	ZNF316	psi-mi:“MI:0914”(association)	0.530
PIGT	ZNF609	psi-mi:“MI:0914”(association)	0.530
HGF	SRPX2	psi-mi:“MI:0407”(direct interaction)	0.440
	SRPX2	psi-mi:“MI:0915”(physical association)	0.370
A2M	SRPX2	psi-mi:“MI:0914”(association)	0.350
C1orf54	QSOX1	psi-mi:“MI:0914”(association)	0.350
C1QTNF9B	DNASE2	psi-mi:“MI:0914”(association)	0.350
FBLN7	SRPX2	psi-mi:“MI:0914”(association)	0.350
MOGS	SRPX2	psi-mi:“MI:0914”(association)	0.350
NTNG1	SRPX2	psi-mi:“MI:0914”(association)	0.350

ESM2 similar proteins: A0A1D5NSM8, A2AVA0, B1AUH1, B3DK56, B5DF94, D3YXF5, O08747, O14522, O60687, O75339, O95185, O97827, P06681, P0C6B8, P10493, P10643, P14543, P21180, P28827, P35822, P82987, Q14112, Q15262, Q3SYW2, Q4LDE5, Q5E9P5, Q5EA25, Q5G872, Q5RAD0, Q5RDI1, Q66K08, Q66PY1, Q6DIV5, Q6GP28, Q6NZL8, Q6UXH9, Q6YI48, Q761X5, Q7T2Z5, Q863A0

Diamond homologs: A0A1D5NSM8, B5DF94, O60687, P08607, P0C6B8, P42201, P78539, P98109, Q2VPA4, Q3SYW2, Q5EA25, Q63769, Q6GP28, Q6QD51, Q76M96, Q8R054, Q8R2G6, Q9R0M3, P04186, P16109, P98105, A2AVA0, C1IBY0, P00751, P00758, P06681, P08884, P17927, P19006, P19007, P20851, P21180, P28175, P33703, P81187, P81475, Q01339, Q03710, Q22328, Q26422

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	101
Likely benign	49
Benign	18

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
4076046	GRCh37/hg19 Xq13.1-27.1(chrX:71017904-140066710)x4	Pathogenic
915418	NM_014467.3(SRPX2):c.1183C>T (p.Gln395Ter)	Pathogenic
450679	NM_014467.3(SRPX2):c.718C>T (p.Arg240Cys)	Likely pathogenic

SpliceAI

1805 predictions. Top by Δscore:

Variant	Effect	Δscore
X:100650694:G:GT	donor_gain	1.0000
X:100650778:A:AG	acceptor_gain	1.0000
X:100650779:TTCTA:T	acceptor_loss	1.0000
X:100650780:TCTA:T	acceptor_loss	1.0000
X:100650781:CTAG:C	acceptor_loss	1.0000
X:100650782:TAGG:T	acceptor_loss	1.0000
X:100650783:A:AG	acceptor_gain	1.0000
X:100650783:A:AT	acceptor_loss	1.0000
X:100650784:G:GG	acceptor_gain	1.0000
X:100666930:GCTC:G	donor_gain	1.0000
X:100666934:G:GG	donor_gain	1.0000
X:100667269:CCTA:C	acceptor_loss	1.0000
X:100667270:CTA:C	acceptor_loss	1.0000
X:100667271:TA:T	acceptor_loss	1.0000
X:100667272:A:AG	acceptor_gain	1.0000
X:100667272:A:AT	acceptor_loss	1.0000
X:100667273:G:GA	acceptor_gain	1.0000
X:100667273:GC:G	acceptor_gain	1.0000
X:100667273:GCT:G	acceptor_gain	1.0000
X:100667273:GCTAT:G	acceptor_gain	1.0000
X:100667408:G:C	donor_loss	1.0000
X:100667408:G:GG	donor_gain	1.0000
X:100669242:TCCCA:T	acceptor_loss	1.0000
X:100669243:CCCA:C	acceptor_loss	1.0000
X:100669244:CCA:C	acceptor_loss	1.0000
X:100669245:CAGCA:C	acceptor_loss	1.0000
X:100669246:A:AG	acceptor_gain	1.0000
X:100669246:AG:A	acceptor_loss	1.0000
X:100669247:G:GT	acceptor_gain	1.0000
X:100669247:GC:G	acceptor_gain	1.0000

AlphaMissense

3008 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:100662343:T:A	W111R	1.000
X:100662343:T:C	W111R	1.000
X:100662345:G:C	W111C	1.000
X:100662345:G:T	W111C	1.000
X:100664923:T:A	W169R	1.000
X:100664923:T:C	W169R	1.000
X:100664925:G:C	W169C	1.000
X:100664925:G:T	W169C	1.000
X:100665325:G:C	W205C	1.000
X:100665325:G:T	W205C	1.000
X:100666908:G:C	W312C	1.000
X:100666908:G:T	W312C	1.000
X:100662186:G:C	W58C	0.999
X:100662186:G:T	W58C	0.999
X:100662187:T:A	C59S	0.999
X:100662188:G:C	C59S	0.999
X:100662271:T:A	C87S	0.999
X:100662272:G:C	C87S	0.999
X:100662284:G:A	C91Y	0.999
X:100662325:T:A	C105S	0.999
X:100662325:T:C	C105R	0.999
X:100662326:G:C	C105S	0.999
X:100662327:C:G	C105W	0.999
X:100662361:T:A	C117S	0.999
X:100662362:G:C	C117S	0.999
X:100664782:T:A	C122S	0.999
X:100664783:G:C	C122S	0.999
X:100664851:T:A	C145S	0.999
X:100664852:G:C	C145S	0.999
X:100664905:T:A	C163S	0.999

dbSNP variants (sampled 300 via entrez): RS1000259874 (X:100643060 C>T), RS1000320960 (X:100669459 T>C), RS1000406380 (X:100650708 G>T), RS1000656986 (X:100671626 G>A,C), RS1000893151 (X:100662040 A>G), RS1001120148 (X:100660943 A>C), RS1001322261 (X:100642258 A>T), RS1001595754 (X:100651297 T>C), RS1002384785 (X:100661493 C>T), RS1002479436 (X:100660932 C>T), RS1002655882 (X:100648977 A>T), RS1002728250 (X:100643254 G>A), RS1002859065 (X:100671532 G>A), RS1002894204 (X:100666393 A>C), RS1002931535 (X:100642992 A>G)

Disease associations

OMIM: gene MIM:300642 | disease phenotypes: MIM:300643, MIM:308350

GenCC curated gene-disease

Disease	Classification	Inheritance
rolandic epilepsy-speech dyspraxia syndrome	Supportive	Autosomal dominant
rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked	Limited	X-linked
polymicrogyria, bilateral perisylvian, X-linked	Limited	X-linked

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
epilepsy	Refuted	XL

Mondo (5): rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked (MONDO:0010388), epilepsy (MONDO:0005027), genetic developmental and epileptic encephalopathy (MONDO:0100062), rolandic epilepsy-speech dyspraxia syndrome (MONDO:0015587), polymicrogyria, bilateral perisylvian, X-linked (MONDO:0010314)

Orphanet (0):

HPO phenotypes

78 total (30 of 78 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000252	Microcephaly
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000453	Choanal atresia
HP:0000639	Nystagmus
HP:0000712	Emotional lability
HP:0000716	Depression
HP:0000736	Short attention span
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development
HP:0000767	Pectus excavatum
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001256	Mild intellectual disability
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001310	Dysmetria
HP:0001320	Cerebellar vermis hypoplasia
HP:0001326	EEG with irregular generalized spike and wave complexes
HP:0001328	Specific learning disability
HP:0001347	Hyperreflexia
HP:0001349	Facial diplegia
HP:0001371	Flexion contracture
HP:0001511	Intrauterine growth retardation
HP:0001611	Hypernasal speech
HP:0002015	Dysphagia
HP:0002020	Gastroesophageal reflux
HP:0002061	Lower limb spasticity

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D004827	Epilepsy	C10.228.140.490
C564467	Rolandic Epilepsy, Mental Retardation, and Speech Dyspraxia, X-Linked (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	5
sodium arsenite	decreases expression, increases expression	2
Acetaminophen	decreases expression, increases expression	2
Dexamethasone	increases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tretinoin	increases expression	2
Valproic Acid	increases expression	2
Cyclosporine	decreases expression, increases expression	2
Aflatoxin B1	affects expression, increases expression	2
methyleugenol	increases expression	1
bisphenol A	affects cotreatment, increases expression	1
ethyl-p-hydroxybenzoate	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
rutecarpine	decreases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Troglitazone	increases expression	1
Leflunomide	increases expression	1
Cisplatin	decreases expression, affects cotreatment	1
Diethylnitrosamine	increases expression	1
Doxorubicin	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Lead	affects expression	1
Mustard Gas	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D8BF	Ubigene A-549 SRPX2 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00004637	PHASE4	COMPLETED	Double-Blind, Placebo-Controlled Trial of Vitamin E as Add-on Therapy for Children With Epilepsy
NCT00043914	PHASE4	COMPLETED	Measurement Of Serum Levels Of Two Antiepileptic Drugs During Conversion In Patients With Epilepsy
NCT00132223	PHASE4	UNKNOWN	Effects on the Diagnostic Accuracy of Magnetic Imaging Angiographies of the Supra-Aortic Vessels by Three Different Magnetic Resonance Contrast Agents in Patients
NCT00133081	PHASE4	UNKNOWN	Study to Improve the Treatment of Epilepsy (SITE)
NCT00137709	PHASE4	UNKNOWN	Hormone Profiles in Adults With Newly Diagnosed Epilepsy
NCT00154076	PHASE4	COMPLETED	A Multicenter Comparative Trial of Zonisamide and Topiramate as Initial Monotherapy in Untreated Epilepsies
NCT00165828	PHASE4	TERMINATED	Efficacy and Safety of an add-on Treatment With Zonisamide in Adults With Focal Epileptic Seizures With or Without Secondary Generalization
NCT00181116	PHASE4	COMPLETED	Levetiracetam for Benign Rolandic Epilepsy
NCT00207935	PHASE4	COMPLETED	Use of Sustained Release Antiepileptic Medication (Depakote® ER) for Pediatric Epilepsy in a Mental Retardation/Developmental Disorder Population
NCT00215592	PHASE4	COMPLETED	Open Label, Zonegran (Zonisamide) In Partial Onset Seizures
NCT00266604	PHASE4	COMPLETED	A Study to Evaluate the Dosing, Effectiveness and Safety of Topiramate for the Treatment of Epilepsy
NCT00288639	PHASE4	COMPLETED	Lyrica (Pregabalin) Administered as an Add-on Therapy for Partial Seizures (LEADER).
NCT00312676	PHASE4	UNKNOWN	Compare Tolerability of an Overnight Switch to Gradual Switch Between Two Different Forms of Depakote
NCT00323947	PHASE4	COMPLETED	Methylphenidate for Treating Attention Deficit Hyperactivity Disorder in Children With Both ADHD and Epilepsy
NCT00385411	PHASE4	COMPLETED	Study of Valproate in Young Patients Suffering From Epilepsy
NCT00522418	PHASE4	TERMINATED	Study Comparing Best Medical Practice With or Without VNS Therapy in Pharmacoresistant Partial Epilepsy Patients
NCT00537940	PHASE4	COMPLETED	Comparative Study Of Pregabalin And Gabapentin As Adjunctive Therapy In Subjects With Partial Seizures
NCT00552526	PHASE4	UNKNOWN	Ketogenic Diet vs.Antiepileptic Drug Treatment in Drug Resistant Epilepsy
NCT00564915	PHASE4	COMPLETED	RCT of the Efficacy of the Ketogenic Diet in the Treatment of Epilepsy
NCT00571155	PHASE4	COMPLETED	Trial of Levetiracetam in Patients With Primary Brain Tumors and Symptomatic Seizures Who Undergo Surgery
NCT00572195	PHASE4	COMPLETED	RNS® System LTT Study
NCT00610532	PHASE4	TERMINATED	Evaluating the Transporter Protein Inhibitor Probenecid In Patients With Epilepsy
NCT00630357	PHASE4	COMPLETED	Trial to Evaluate the Safety and Efficacy of Keppra After Conversion to Mono-therapy in Subjects With Partial Epilepsy
NCT00630630	PHASE4	COMPLETED	Study on Safety and Efficacy of Levetiracetam in the Adjunctive Treatment of Female Subjects With C1 Catamenial Epilepsy
NCT00630968	PHASE4	COMPLETED	S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00631150	PHASE4	COMPLETED	A Phase IV-Pharmacovigilance Study of Keppra Greece - S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00659958	PHASE4	COMPLETED	ZAGAL Study: Evaluating Effectiveness and Tolerability of Zonisamide as Adjunctive Therapy in Patients With Partial Onset Seizures Treated With Two Antiepileptic Drugs
NCT00713622	PHASE4	COMPLETED	Comparing The Effect On Cognition Of Adjunctive Therapy With Zonisamide Versus Sodium Valproate
NCT00807989	PHASE4	COMPLETED	The Efficacy and Safety of Low Dose Combination of LTG and VPA Compared to CBZ Monotherapy
NCT00832884	PHASE4	COMPLETED	The Safety of Intravenous Lacosamide
NCT00869622	PHASE4	COMPLETED	Antiepileptic Drugs and Osteoporotic Prevention Trial
NCT00896987	PHASE4	COMPLETED	Lamotrigine Cognitive Function Study in Adult Untreated Epilepsies
NCT00952081	PHASE4	COMPLETED	A Pilot Study to Evaluate Efficacy and Safety of Clevidipine in Neurosurgical Patients
NCT01118455	PHASE4	TERMINATED	Trial to Assess Vagus Nerve Stimulation Therapy vs. Anti-Epileptic Drug (AED) Treatment in Children With Refractory Seizures
NCT01127165	PHASE4	COMPLETED	Low and High Dose Zonisamide in Children as Monotherapy
NCT01127256	PHASE4	COMPLETED	Comparative Study of Zonisamide and Carbamazepine as an Initial Monotherapy: Efficacy and Safety Evaluation
NCT01140867	PHASE4	COMPLETED	Open-label, Multi-center Trial of Zonisamide as Adjunctive Therapy in Patients With Uncontrolled Partial Epilepsy
NCT01175954	PHASE4	COMPLETED	Cognitive and Behavioral Effects of Lacosamide
NCT01229735	PHASE4	COMPLETED	Levetiracetam Versus Topiramate as Adjunctive Therapy to Evaluate Efficacy and Safety in Subjects With Refractory Partial Onset Seizures
NCT01244724	PHASE4	TERMINATED	Lexapro for Major Depression in Patients With Epilepsy