Intellectual developmental disorder with polymicrogyria and seizures

Summary

Intellectual developmental disorder with polymicrogyria and seizures (MONDO:0976124) is a disease caused by TCP1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: TCP1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual developmental disorder with polymicrogyria and seizures
Mondo ID	MONDO:0976124
OMIM	621021
UMLS	C5975535
MedGen	1875065
Is cancer (heuristic)	no

Data availability: 4 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › neurodevelopmental disorder › intellectual disability › intellectual developmental disorder with polymicrogyria and seizures

Related subtypes (9): syndromic intellectual disability, non-syndromic intellectual disability, intellectual developmental disorder and retinitis pigmentosa; IDDRP, PPP2R1A-related intellectual disability, intellectual disability, autosomal dominant, X-linked intellectual disability, intellectual disability, autosomal recessive, NACC1-related neurodevelopmental disorder with epilepsy, cataracts and episodic irritability, SETD2-related neurodevelopmental disorder without or with macrocephaly/overgrowth

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

4 retrieved; paginated sample, class counts are floors:

4 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3544396	NM_030752.3(TCP1):c.583_584del (p.Ser194_Val195insTer)	TCP1	Pathogenic	no assertion criteria provided
3544397	NM_030752.3(TCP1):c.252_255del (p.Glu85fs)	TCP1	Pathogenic	no assertion criteria provided
3544398	NM_030752.3(TCP1):c.1502dup (p.Gly502fs)	TCP1	Pathogenic	no assertion criteria provided
3544399	NM_030752.3(TCP1):c.793_796del (p.Gln265fs)	TCP1	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 0 · 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
TCP1	Strong	Autosomal dominant	intellectual developmental disorder with polymicrogyria and seizures	3

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TCP1	HGNC:11655	ENSG00000120438	P17987	T-complex protein 1 subunit alpha	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TCP1	T-complex protein 1 subunit alpha	Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of actin, tubulin and other proteins upon ATP hydrolysis.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TCP1	Enzyme (other)	yes	3.6.4.B10	Chaperonin_TCP-1_CS, Cpn60/GroEL/TCP-1, Chap_CCT_alpha

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	1
ganglionic eminence	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TCP1	284	ubiquitous	marker	primordial germ cell in gonad, cortical plate, ganglionic eminence

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TCP1	6,691

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TCP1	P17987	65

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 19. Enrichment computed across 1 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
Folding of actin by CCT/TriC	1	1142.0×	0.006	TCP1
BBSome-mediated cargo-targeting to cilium	1	496.5×	0.006	TCP1
Interleukin-12 family signaling	1	475.8×	0.006	TCP1
Formation of tubulin folding intermediates by CCT/TriC	1	423.0×	0.006	TCP1
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	1	407.9×	0.006	TCP1
Interleukin-12 signaling	1	407.9×	0.006	TCP1
Prefoldin mediated transfer of substrate to CCT/TriC	1	393.8×	0.006	TCP1
Chaperonin-mediated protein folding	1	300.5×	0.006	TCP1
Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding	1	300.5×	0.006	TCP1
Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation	1	300.5×	0.006	TCP1
Association of TriC/CCT with target proteins during biosynthesis	1	292.8×	0.006	TCP1
Protein folding	1	259.6×	0.006	TCP1
Cargo trafficking to the periciliary membrane	1	248.3×	0.006	TCP1
Cilium Assembly	1	108.8×	0.012	TCP1
Organelle biogenesis and maintenance	1	66.0×	0.019	TCP1
Signaling by Interleukins	1	64.2×	0.019	TCP1
Cytokine Signaling in Immune system	1	40.8×	0.027	TCP1
Immune System	1	13.0×	0.081	TCP1
Metabolism of proteins	1	12.4×	0.081	TCP1

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of establishment of protein localization to telomere	1	5617.3×	0.001	TCP1
scaRNA localization to Cajal body	1	3370.4×	0.001	TCP1
positive regulation of telomerase RNA localization to Cajal body	1	1872.4×	0.001	TCP1
tubulin complex assembly	1	1685.2×	0.001	TCP1
positive regulation of protein localization to Cajal body	1	1685.2×	0.001	TCP1
positive regulation of telomere maintenance via telomerase	1	732.7×	0.002	TCP1
binding of sperm to zona pellucida	1	421.3×	0.003	TCP1
protein folding	1	103.4×	0.011	TCP1
protein stabilization	1	66.9×	0.015	TCP1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TCP1	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	TCP1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
TCP1	7	Binding:7

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TCP1	3.6.4.B10

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

1 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.

Compound	Max phase	Cohort target (bioactivity)
MOLIBRESIB	2	TCP1

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	1	TCP1
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.