SRPX2

sushi repeat containing protein X-linked 2, the group of Sushi domain containing

Basic information

Region (hg38): X:100644195-100675788

Links

ENSG00000102359 ∙ NCBI:27286 ∙ OMIM:300642 ∙ HGNC:30668 ∙ Uniprot:O60687 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked (Limited), mode of inheritance: XLR
• polymicrogyria, bilateral perisylvian, X-linked (Limited), mode of inheritance: XLR
• rolandic epilepsy-speech dyspraxia syndrome (Supportive), mode of inheritance: AD
• rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked (Disputed Evidence), mode of inheritance: XL
• polymicrogyria, bilateral perisylvian, X-linked (Limited), mode of inheritance: XL
• rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked (Limited), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Rolandic epilepsy, intellectual developmental disorder, and speech dyspraxia, X-linked	XL	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	16497722; 23871722; 24995671
The evidence of variants as being related to disease causation has been questioned due to subsequent population-based studies

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SRPX2 gene.

• Rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SRPX2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	23	1	28
missense		1	65	8		74
nonsense	1		1			2
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)			4			4
splice region				3	1	4
non coding			1	16	16	33
Total	1	1	76	47	17

Variants in SRPX2

This is a list of pathogenic ClinVar variants found in the SRPX2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
X-100644247-G-C			Benign (Jun 10, 2019)
X-100646286-A-G		not specified	Likely benign (Oct 10, 2013)
X-100646339-C-T		Rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked	Uncertain significance (Oct 28, 2017)
X-100646345-G-A			Uncertain significance (Mar 27, 2019)
X-100646371-C-G		Rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked	Uncertain significance (Aug 28, 2019)
X-100646379-G-A		Rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked	Uncertain significance (Sep 19, 2020)
X-100646647-C-T			Likely benign (Jun 14, 2018)
X-100650685-T-C			Benign (Jun 28, 2018)
X-100650801-G-A		Rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked	Uncertain significance (Aug 06, 2021)
X-100650801-G-T		Rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked	Likely benign (Mar 06, 2020)
X-100650812-A-ACAATGAAGTATATGCAGAGGAGGTCCCACAGGCTCCTGCCCTGGACTACCGAGGTAATCTAC		Rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked	Uncertain significance (Oct 08, 2020)
X-100650819-A-C		Rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked	Uncertain significance (Aug 24, 2021)
X-100650820-G-A		Rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked	Uncertain significance (Apr 25, 2022)
X-100650829-G-A		SRPX2-related disorder	Uncertain significance (Jul 29, 2016)
X-100650862-C-A		Rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked	Likely benign (Aug 23, 2022)
X-100650862-C-T			Uncertain significance (Aug 27, 2024)
X-100650863-G-A		Rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked • not specified	Uncertain significance (Feb 07, 2023)
X-100650877-T-C		not specified • Rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked	Benign (Aug 19, 2023)
X-100651156-T-G			Benign (Jul 15, 2018)
X-100651158-G-T			Likely benign (Nov 29, 2019)
X-100661933-GT-G			Benign (Dec 10, 2019)
X-100661933-GTT-G			Likely benign (Jan 20, 2020)
X-100661933-G-GT			Benign (Aug 21, 2019)
X-100661942-T-G			Likely benign (Apr 24, 2020)
X-100661945-T-G			Likely benign (Apr 08, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SRPX2	protein_coding	protein_coding	ENST00000373004	10	27082

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0481	0.952	125735	4	4	125743	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.226	204	213	0.956	0.0000187	2996
Missense in Polyphen		78	88.715	0.87922		1156
Synonymous	1.21	62	75.3	0.823	0.00000618	918
Loss of Function	3.27	7	24.4	0.286	0.00000235	300

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000112	0.0000980
Ashkenazi Jewish	0.000134	0.0000992
East Asian	0.0000744	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000264	0.0000176
Middle Eastern	0.0000744	0.0000544
South Asian	0.000162	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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. {ECO:0000269|PubMed:16497722, ECO:0000269|PubMed:18718938, ECO:0000269|PubMed:19065654, ECO:0000269|PubMed:24179158}.
• Disease: DISEASE: Rolandic epilepsy with speech dyspraxia and mental retardation X-linked (RESDX) [MIM:300643]: A condition characterized by the association of rolandic seizures with oral and speech dyspraxia, and mental retardation. 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. {ECO:0000269|PubMed:16497722}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Pregnane X Receptor pathway;Nuclear Receptors Meta-Pathway;Liver steatosis AOP (Consensus)

Recessive Scores

• pRec: 0.138

Intolerance Scores

• loftool: 0.464
• rvis_EVS: 0.17
• rvis_percentile_EVS: 65.96

Haploinsufficiency Scores

• pHI: 0.309
• hipred: Y
• hipred_score: 0.644
• ghis: 0.516

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0211

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Srpx2
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: angiogenesis;regulation of phosphorylation;cell motility;positive regulation of synapse assembly;vocalization behavior;positive regulation of cell migration involved in sprouting angiogenesis;cell-cell adhesion
• Cellular component: extracellular space;cytoplasm;cell surface;cell junction;excitatory synapse;synaptic membrane
• Molecular function: signaling receptor binding;protein binding;hepatocyte growth factor binding;identical protein binding