rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked

Summary

rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked (MONDO:0010388) is a disease with 3 cohort genes.

At a glance

• Cohort genes: 3
• ClinVar variants: 95

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked
Mondo ID	MONDO:0010388
MeSH	C564467
OMIM	300643
UMLS	C1845070
MedGen	337150
GARD	0018282
Is cancer (heuristic)	no

Also known as: RESDX · rolandic epilepsy, impaired intellectual development, and speech dyspraxia · rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked · ROLANDIC epilepsy, mental retardation, and speech dyspraxia, X-linked · rolandic epilepsy, mental retardation, and speech dyspraxia, X-linked

Data availability: 95 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › epilepsy › epilepsy syndrome › childhood-onset epilepsy syndrome › rolandic epilepsy-speech dyspraxia syndrome › rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked

Related subtypes (1): GRIN2A-related rolandic epilepsy-speech dyspraxia syndrome

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

95 retrieved; paginated sample, class counts are floors:

45 uncertain significance, 23 likely benign, 18 conflicting classifications of pathogenicity, 4 benign/likely benign, 4 benign, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
915418	NM_014467.3(SRPX2):c.1183C>T (p.Gln395Ter)	SRPX2	Pathogenic	criteria provided, single submitter
10775	NM_014467.3(SRPX2):c.980A>G (p.Asn327Ser)	SRPX2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
139323	NM_014467.3(SRPX2):c.460C>G (p.His154Asp)	SRPX2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
198562	NM_014467.3(SRPX2):c.693C>A (p.His231Gln)	SRPX2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
207383	NM_014467.3(SRPX2):c.809C>T (p.Pro270Leu)	SRPX2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
207384	NM_014467.3(SRPX2):c.1199A>G (p.Asn400Ser)	SRPX2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
207386	NM_014467.3(SRPX2):c.1229G>A (p.Arg410His)	SRPX2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
207387	NM_014467.3(SRPX2):c.224A>T (p.Lys75Met)	SRPX2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
207388	NM_014467.3(SRPX2):c.248T>C (p.Leu83Pro)	SRPX2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
207393	NM_014467.3(SRPX2):c.893G>A (p.Arg298His)	SRPX2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
207395	NM_014467.3(SRPX2):c.1030C>A (p.Leu344Ile)	SRPX2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
207400	NM_014467.3(SRPX2):c.928C>T (p.Arg310Cys)	SRPX2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
284208	NM_014467.3(SRPX2):c.646G>A (p.Gly216Ser)	SRPX2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
378669	NM_014467.3(SRPX2):c.323G>A (p.Ser108Asn)	SRPX2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
533652	NM_014467.3(SRPX2):c.982G>A (p.Val328Ile)	SRPX2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
590220	NM_014467.3(SRPX2):c.737G>A (p.Arg246Gln)	SRPX2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
95601	NM_014467.3(SRPX2):c.605G>A (p.Arg202Gln)	SRPX2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
95602	NM_014467.3(SRPX2):c.840G>A (p.Ala280=)	SRPX2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
465294	NC_000023.10:g.(?99551255)(99926004_?)del	TSPAN6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
417465	NC_000023.11:g.(?100644166)(100671299_?)del	LOC121627976	Uncertain significance	criteria provided, single submitter
1007485	NM_014467.3(SRPX2):c.371C>T (p.Ala124Val)	SRPX2	Uncertain significance	criteria provided, single submitter
1013627	NM_014467.3(SRPX2):c.1129A>G (p.Thr377Ala)	SRPX2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1022758	NM_014467.3(SRPX2):c.554G>T (p.Arg185Leu)	SRPX2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1025666	NM_014467.3(SRPX2):c.553C>T (p.Arg185Cys)	SRPX2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1035311	NM_014467.3(SRPX2):c.112_163+10dup	SRPX2	Uncertain significance	criteria provided, single submitter
1038364	NM_014467.3(SRPX2):c.656C>G (p.Thr219Ser)	SRPX2	Uncertain significance	criteria provided, single submitter
1041828	NM_014467.3(SRPX2):c.961+1G>A	SRPX2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1044918	NM_014467.3(SRPX2):c.1288C>T (p.Arg430Cys)	SRPX2	Uncertain significance	criteria provided, single submitter
1051415	NM_014467.3(SRPX2):c.959C>T (p.Ala320Val)	SRPX2	Uncertain significance	criteria provided, single submitter
10776	NM_014467.3(SRPX2):c.215A>C (p.Tyr72Ser)	SRPX2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
SRPX2	Supportive	Autosomal dominant	rolandic epilepsy-speech dyspraxia syndrome	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SRPX2	Orphanet:163721	Rolandic epilepsy-speech dyspraxia syndrome
SRPX2	Orphanet:1945	Self-limited epilepsy with centrotemporal spikes
SRPX2	Orphanet:98889	Bilateral perisylvian polymicrogyria

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SRPX2	HGNC:30668	ENSG00000102359	O60687	Sushi repeat-containing protein SRPX2	gencc,clinvar
TAF7L	HGNC:11548	ENSG00000102387	Q5H9L4	Transcription initiation factor TFIID subunit 7-like	clinvar
TSPAN6	HGNC:11858	ENSG00000000003	O43657	Tetraspanin-6	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SRPX2	Sushi repeat-containing protein SRPX2	Acts as a ligand for the urokinase plasminogen activator surface receptor.
TAF7L	Transcription initiation factor TFIID subunit 7-like	Probably functions as a spermatogenesis-specific component of the DNA-binding general transcription factor complex TFIID, a multimeric protein complex that plays a central role in mediating promoter responses to various activators and repr…

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Complement	1	89.3×	0.022
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SRPX2	Complement	yes		Sushi_SCR_CCP_dom, HYR_dom, DUF4174
TAF7L	Other/Unknown	no		TAFII55_prot_cons_reg, TAF7
TSPAN6	Other/Unknown	no		Tetraspanin_animals, Tetraspanin_EC2_sf, Tetraspanin/Peripherin

Expression context

Cohort genes with no expression data: 0.

3 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	1
cartilage tissue	1
stromal cell of endometrium	1
left testis	1
primordial germ cell in gonad	1
right testis	1
bronchial epithelial cell	1
parotid gland	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SRPX2	211	ubiquitous	marker	stromal cell of endometrium, calcaneal tendon, cartilage tissue
TAF7L	136	tissue_specific	marker	right testis, left testis, primordial germ cell in gonad
TSPAN6	279	ubiquitous	marker	sperm, parotid gland, bronchial epithelial cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TSPAN6	1,046
TAF7L	984
SRPX2	954

Structural data

PDB: 0 · AlphaFold-only: 3 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TSPAN6	O43657	88.17
SRPX2	O60687	86.75
TAF7L	Q5H9L4	68.14

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 20. Enrichment computed across 3 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
HIV Transcription Initiation	1	233.1×	0.013	TAF7L
RNA Polymerase II HIV Promoter Escape	1	233.1×	0.013	TAF7L
RNA Polymerase II Promoter Escape	1	233.1×	0.013	TAF7L
RNA Polymerase II Transcription Pre-Initiation And Promoter Opening	1	233.1×	0.013	TAF7L
RNA Polymerase II Transcription Initiation	1	233.1×	0.013	TAF7L
RNA Polymerase II Transcription Initiation And Promoter Clearance	1	233.1×	0.013	TAF7L
Transcription of the HIV genome	1	173.0×	0.013	TAF7L
Late Phase of HIV Life Cycle	1	167.9×	0.013	TAF7L
HIV Life Cycle	1	160.8×	0.013	TAF7L
RNA Polymerase II Pre-transcription Events	1	137.6×	0.013	TAF7L
Regulation of TP53 Activity	1	132.8×	0.013	TAF7L
HIV Infection	1	119.0×	0.013	TAF7L
Regulation of TP53 Activity through Phosphorylation	1	117.7×	0.013	TAF7L
Transcriptional Regulation by TP53	1	62.1×	0.023	TAF7L
Viral Infection Pathways	1	30.8×	0.043	TAF7L
Infectious disease	1	24.8×	0.050	TAF7L
RNA Polymerase II Transcription	1	22.5×	0.052	TAF7L
Gene expression (Transcription)	1	17.8×	0.062	TAF7L
Generic Transcription Pathway	1	15.1×	0.070	TAF7L
Disease	1	13.1×	0.076	TAF7L

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of phosphorylation	1	936.2×	0.008	SRPX2
negative regulation of cytoplasmic pattern recognition receptor signaling pathway	1	802.5×	0.008	TSPAN6
vocalization behavior	1	295.6×	0.013	SRPX2
positive regulation of cell migration involved in sprouting angiogenesis	1	244.2×	0.013	SRPX2
cell motility	1	133.8×	0.019	SRPX2
RNA polymerase II preinitiation complex assembly	1	90.6×	0.023	TAF7L
positive regulation of synapse assembly	1	81.4×	0.023	SRPX2
negative regulation of canonical NF-kappaB signal transduction	1	57.3×	0.028	TSPAN6
cell-cell adhesion	1	33.8×	0.042	SRPX2
positive regulation of canonical NF-kappaB signal transduction	1	24.2×	0.053	TSPAN6
angiogenesis	1	20.8×	0.056	SRPX2
spermatogenesis	1	11.7×	0.090	TAF7L
cell differentiation	1	9.7×	0.100	TAF7L

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 3

Druggability breadth: 0 of 3 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SRPX2	0	0
TAF7L	0	0
TSPAN6	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	SRPX2
E	Difficult family or no structure, no drug	2	TAF7L, TSPAN6

Undrugged target profiles

3 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
SRPX2	0	—
TAF7L	0	—
TSPAN6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.