SRPX2

Chr X

sushi repeat containing protein X-linked 2

Also known as: BPP, CBPS, PMGX, RESDX, SRPUL

The SRPX2 protein is secreted and contains sushi repeat motifs, functioning as a ligand for the urokinase plasminogen activator surface receptor and promoting synapse formation, angiogenesis, and cellular migration. Mutations cause X-linked rolandic epilepsy with impaired intellectual development and speech dyspraxia, typically affecting the perisylvian brain region critical for language and cognitive development. This gene shows low constraint against loss-of-function variants (LOEUF 0.538), consistent with X-linked inheritance where hemizygous males are primarily affected.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

?Rolandic epilepsy, impaired intellectual development, and speech dyspraxiaMIM #300643
0
Active trials
10
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.54
LOEUF
DN
Mechanism· predicted
Clinical SummarySRPX2
🧬
Gene-Disease Validity (ClinGen)
epilepsy · XLRefuted

Refuted — evidence has disproved this relationship

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.
📖
GeneReview available — SRPX2
Authoritative clinical overview · Recommended first read
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Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.54LOEUF
pLI 0.048
Z-score 3.27
OE 0.29 (0.160.54)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.23Z-score
OE missense 0.96 (0.851.07)
204 obs / 213.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.29 (0.160.54)
00.351.4
Missense OE0.96 (0.851.07)
00.61.4
Synonymous OE0.82
01.21.6
LoF obs/exp: 7 / 24.4Missense obs/exp: 204 / 213.3Syn Z: 1.21
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedSRPX2-related bilateral perisylvian polymicrogyriaOTHERXLR
DN
0.6937th %ile
GOF
0.5760th %ile
LOF
0.2872th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SRPX2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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