Complex cortical dysplasia with other brain malformations 2

disease

On this page

Also known as CDCBM2complex cortical dysplasia with other brain malformations caused by mutation in KIF5Ccomplex cortical dysplasia with other brain malformations type 2cortical dysplasia, complex, with other brain malformations 2cortical dysplasia, Complex, with Other brain malformations type 2KIF5C complex cortical dysplasia with other brain malformations

Summary

Complex cortical dysplasia with other brain malformations 2 (MONDO:0014116) is a disease caused by KIF5C (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: KIF5C (GenCC Strong)
Cohort genes: 1
ClinVar variants: 40

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	complex cortical dysplasia with other brain malformations 2
Mondo ID	MONDO:0014116
OMIM	615282
DOID	DOID:0090133
UMLS	C3809013
MedGen	815343
Is cancer (heuristic)	no

Also known as: CDCBM2 · complex cortical dysplasia with other brain malformations caused by mutation in KIF5C · complex cortical dysplasia with other brain malformations type 2 · cortical dysplasia, complex, with other brain malformations 2 · cortical dysplasia, Complex, with Other brain malformations type 2 · KIF5C complex cortical dysplasia with other brain malformations

Data availability: 40 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 › complex cortical dysplasia with other brain malformations › complex cortical dysplasia with other brain malformations 2

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

40 retrieved; paginated sample, class counts are floors:

23 uncertain significance, 6 likely pathogenic, 4 likely benign, 3 pathogenic/likely pathogenic, 3 conflicting classifications of pathogenicity, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1333049	NM_004522.3(KIF5C):c.278C>T (p.Thr93Ile)	KIF5C	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
140740	NM_004522.3(KIF5C):c.709G>A (p.Glu237Lys)	KIF5C	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1878628	NM_004522.3(KIF5C):c.265T>C (p.Ser89Pro)	KIF5C	Pathogenic	criteria provided, single submitter
504269	NM_004522.3(KIF5C):c.265TCA[1] (p.Ser90del)	KIF5C	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2443686	NM_004522.3(KIF5C):c.275A>G (p.Lys92Arg)	KIF5C	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2498166	NM_004522.3(KIF5C):c.710A>G (p.Glu237Gly)	KIF5C	Likely pathogenic	criteria provided, single submitter
3384044	NM_004522.3(KIF5C):c.404A>G (p.Tyr135Cys)	KIF5C	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3385394	NM_004522.3(KIF5C):c.1666A>T (p.Lys556Ter)	KIF5C	Likely pathogenic	criteria provided, single submitter
3385396	NM_004522.3(KIF5C):c.2385dup (p.Gln796fs)	KIF5C	Likely pathogenic	criteria provided, single submitter
65402	NM_004522.3(KIF5C):c.710A>T (p.Glu237Val)	KIF5C	Likely pathogenic	criteria provided, single submitter
1341342	NM_004522.3(KIF5C):c.1964G>A (p.Arg655Lys)	KIF5C	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1711507	NM_004522.3(KIF5C):c.2675G>A (p.Arg892Gln)	KIF5C	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3385395	NM_004522.3(KIF5C):c.2282_2283del (p.Gln761fs)	KIF5C	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1339229	NM_004522.3(KIF5C):c.1454A>C (p.Lys485Thr)	KIF5C	Uncertain significance	criteria provided, single submitter
1341828	NM_004522.3(KIF5C):c.952C>A (p.Leu318Met)	KIF5C	Uncertain significance	criteria provided, single submitter
1699156	NM_004522.3(KIF5C):c.1700C>T (p.Thr567Ile)	KIF5C	Uncertain significance	criteria provided, single submitter
1708124	NM_004522.3(KIF5C):c.1358A>G (p.Asp453Gly)	KIF5C	Uncertain significance	criteria provided, single submitter
1805970	NM_004522.3(KIF5C):c.2640G>C (p.Glu880Asp)	KIF5C	Uncertain significance	criteria provided, single submitter
2433156	NM_004522.3(KIF5C):c.2672T>C (p.Met891Thr)	KIF5C	Uncertain significance	criteria provided, multiple submitters, no conflicts
2433157	NM_004522.3(KIF5C):c.2618C>T (p.Ala873Val)	KIF5C	Uncertain significance	criteria provided, single submitter
2433158	NM_004522.3(KIF5C):c.1187C>A (p.Thr396Asn)	KIF5C	Uncertain significance	criteria provided, multiple submitters, no conflicts
2441708	NM_004522.3(KIF5C):c.610A>G (p.Arg204Gly)	KIF5C	Uncertain significance	criteria provided, single submitter
2441978	NM_004522.3(KIF5C):c.571C>T (p.Arg191Ter)	KIF5C	Uncertain significance	criteria provided, single submitter
2689315	NM_004522.3(KIF5C):c.2230C>G (p.Leu744Val)	KIF5C	Uncertain significance	criteria provided, single submitter
3148961	NM_004522.3(KIF5C):c.1771A>G (p.Ile591Val)	KIF5C	Uncertain significance	criteria provided, single submitter
3391382	NM_004522.3(KIF5C):c.2722G>A (p.Val908Met)	KIF5C	Uncertain significance	criteria provided, single submitter
3393304	NM_004522.3(KIF5C):c.1899C>G (p.Ile633Met)	KIF5C	Uncertain significance	criteria provided, single submitter
3393311	NM_004522.3(KIF5C):c.2291A>G (p.Glu764Gly)	KIF5C	Uncertain significance	criteria provided, single submitter
3775839	NM_004522.3(KIF5C):c.228A>C (p.Glu76Asp)	KIF5C	Uncertain significance	criteria provided, single submitter
4079110	NM_004522.3(KIF5C):c.2115G>C (p.Gln705His)	KIF5C	Uncertain significance	criteria provided, single submitter

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
KIF5C	Strong	Autosomal dominant	complex cortical dysplasia with other brain malformations 2	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
KIF5C	HGNC:6325	ENSG00000168280	O60282	Kinesin heavy chain isoform 5C	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KIF5C	Kinesin heavy chain isoform 5C	Microtubule-associated force-producing protein that may play a role in organelle transport.

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)
KIF5C	Other/Unknown	no		Kinesin_motor_dom, Kinesin_motor_CS, P-loop_NTPase

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
Brodmann (1909) area 10	1
frontal pole	1
paraflocculus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KIF5C	229	broad	marker	Brodmann (1909) area 10, paraflocculus, frontal pole

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KIF5C	2,900

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KIF5C	O60282	78.70

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Insulin processing	1	456.8×	0.006	KIF5C
Peptide hormone metabolism	1	271.9×	0.006	KIF5C
Metabolism of proteins	1	12.4×	0.081	KIF5C

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
anterograde dendritic transport of messenger ribonucleoprotein complex	1	5617.3×	9e-04	KIF5C
organelle organization	1	3370.4×	9e-04	KIF5C
anterograde dendritic transport of neurotransmitter receptor complex	1	2407.4×	9e-04	KIF5C
intracellular mRNA localization	1	2106.5×	9e-04	KIF5C
anterograde axonal protein transport	1	2106.5×	9e-04	KIF5C
synaptic vesicle transport	1	842.6×	0.002	KIF5C
motor neuron axon guidance	1	702.2×	0.002	KIF5C
mRNA transport	1	263.3×	0.004	KIF5C
axon guidance	1	90.6×	0.011	KIF5C

Therapeutics

Drug target analysis

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

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
KIF5C	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
KIF5C	3	Binding:3

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	KIF5C

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)
KIF5C	3	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: KIF5C