Cortical dysplasia, complex, with other brain malformations 11

disease

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Summary

Cortical dysplasia, complex, with other brain malformations 11 (MONDO:0859332) is a disease caused by KIF26A (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: KIF26A (GenCC Strong)
Cohort genes: 1
ClinVar variants: 17

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cortical dysplasia, complex, with other brain malformations 11
Mondo ID	MONDO:0859332
OMIM	620156
DOID	DOID:0061142
UMLS	C5774270
MedGen	1824043
Is cancer (heuristic)	no

Data availability: 17 ClinVar variants · 5 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 › complex cortical dysplasia with other brain malformations › cortical dysplasia, complex, with other brain malformations 11

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

17 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 5 pathogenic, 5 likely pathogenic, 1 conflicting classifications of pathogenicity, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1802642	NM_015656.2(KIF26A):c.4870C>T (p.Arg1624Cys)	KIF26A	Pathogenic	no assertion criteria provided
1802643	NM_015656.2(KIF26A):c.2845C>T (p.Pro949Ser)	KIF26A	Pathogenic	no assertion criteria provided
1802645	NM_015656.2(KIF26A):c.3440dup (p.Ala1148fs)	KIF26A	Pathogenic	no assertion criteria provided
2683901	NM_015656.2(KIF26A):c.4085dup (p.Ala1363fs)	KIF26A	Pathogenic	criteria provided, single submitter
3233662	NM_015656.2(KIF26A):c.4378del (p.Arg1460fs)	KIF26A	Pathogenic	criteria provided, single submitter
2627109	NM_015656.2(KIF26A):c.3996C>A (p.Cys1332Ter)	KIF26A	Likely pathogenic	criteria provided, single submitter
3064895	NM_015656.2(KIF26A):c.4979_4980del (p.Gly1659_Tyr1660insTer)	KIF26A	Likely pathogenic	criteria provided, single submitter
3362589	NM_015656.2(KIF26A):c.3330del (p.Ser1111fs)	KIF26A	Likely pathogenic	criteria provided, single submitter
4077393	NM_015656.2(KIF26A):c.3282dup (p.Pro1095fs)	KIF26A	Likely pathogenic	criteria provided, single submitter
4849399	NM_015656.2(KIF26A):c.3688C>T (p.Gln1230Ter)	KIF26A	Likely pathogenic	criteria provided, single submitter
1802641	NM_015656.2(KIF26A):c.4676C>T (p.Ala1559Val)	KIF26A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1802640	NM_015656.2(KIF26A):c.2161C>T (p.Arg721Cys)	KIF26A	Uncertain significance	criteria provided, multiple submitters, no conflicts
1802644	NM_015656.2(KIF26A):c.4804C>T (p.Arg1602Trp)	KIF26A	Uncertain significance	criteria provided, single submitter
2356383	NM_015656.2(KIF26A):c.4085C>T (p.Pro1362Leu)	KIF26A	Uncertain significance	criteria provided, multiple submitters, no conflicts
2671916	NM_015656.2(KIF26A):c.3335C>T (p.Ser1112Phe)	KIF26A	Uncertain significance	criteria provided, single submitter
3376441	NM_015656.2(KIF26A):c.1538G>A (p.Arg513His)	KIF26A	Uncertain significance	criteria provided, single submitter
4795892	NM_015656.2(KIF26A):c.1483G>A (p.Ala495Thr)	KIF26A	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
KIF26A	Strong	Autosomal recessive	cortical dysplasia, complex, with other brain malformations 11	5

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
KIF26A	HGNC:20226	ENSG00000066735	Q9ULI4	Kinesin-like protein KIF26A	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KIF26A	Kinesin-like protein KIF26A	Atypical kinesin that plays a key role in enteric neuron development.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KIF26A	Other/Unknown	no		Kinesin_motor_dom, P-loop_NTPase, Kinesin-like_fam

Expression context

Cohort genes with no expression data: 0.

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
ganglionic eminence	1
left ventricle myocardium	1
pancreatic ductal cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KIF26A	169	broad	yes	left ventricle myocardium, pancreatic ductal cell, ganglionic eminence

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KIF26A	1,041

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KIF26A	Q9ULI4	48.09

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. 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
Kinesins	1	178.4×	0.025	KIF26A
Golgi-to-ER retrograde transport	1	132.8×	0.025	KIF26A
COPI-dependent Golgi-to-ER retrograde traffic	1	110.9×	0.025	KIF26A
Intra-Golgi and retrograde Golgi-to-ER traffic	1	104.8×	0.025	KIF26A
MHC class II antigen presentation	1	89.2×	0.025	KIF26A
Factors involved in megakaryocyte development and platelet production	1	66.4×	0.028	KIF26A
Membrane Trafficking	1	37.1×	0.035	KIF26A
Hemostasis	1	36.0×	0.035	KIF26A
Vesicle-mediated transport	1	34.8×	0.035	KIF26A
Adaptive Immune System	1	29.8×	0.037	KIF26A
Immune System	1	13.0×	0.077	KIF26A

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of cell growth by extracellular stimulus	1	4213.0×	0.001	KIF26A
enteric nervous system development	1	991.3×	0.003	KIF26A
regulation of neuron migration	1	624.1×	0.003	KIF26A
regulation of neuron projection development	1	432.1×	0.003	KIF26A
negative regulation of signal transduction	1	374.5×	0.003	KIF26A
cerebral cortex development	1	205.5×	0.005	KIF26A

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 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
KIF26A	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

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	0
E	Difficult family or no structure, no drug	1	KIF26A

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
KIF26A	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: KIF26A