Lissencephaly 10

Summary

Lissencephaly 10 (MONDO:0030031) is a disease caused by CEP85L (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: CEP85L (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 31

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	lissencephaly 10
Mondo ID	MONDO:0030031
OMIM	618873
DOID	DOID:0112229
UMLS	C5394354
MedGen	1719546
GARD	0025512
Is cancer (heuristic)	no

Also known as: LIS10 · LISSENCEPHALY 10 · lissencephaly 10

Data availability: 31 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › lissencephaly spectrum disorders › lissencephaly 10

Related subtypes (14): craniotelencephalic dysplasia, X-linked lissencephaly with abnormal genitalia, lissencephaly 7 with cerebellar hypoplasia, lissencephaly 8, classic lissencephaly, lissencephaly type 3, microlissencephaly, Warburg micro syndrome, Baraitser-Winter cerebrofrontofacial syndrome, cobblestone lissencephaly, lissencephaly with cerebellar hypoplasia, cortical dysplasia, complex, with other brain malformations 9, massa casaer ceulemans syndrome, lissencephaly spectrum disorder with complex brainstem malformation

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

31 retrieved; paginated sample, class counts are floors:

16 uncertain significance, 4 benign, 4 likely pathogenic, 3 pathogenic/likely pathogenic, 2 conflicting classifications of pathogenicity, 1 likely benign, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
872889	NM_001042475.3(CEP85L):c.2T>C (p.Met1Thr)	CEP85L	Pathogenic	criteria provided, single submitter
872891	NM_001042475.3(CEP85L):c.203T>C (p.Ile68Thr)	CEP85L	Pathogenic/Likely pathogenic	no assertion criteria provided
872892	NM_001042475.3(CEP85L):c.232+3G>T	CEP85L	Pathogenic/Likely pathogenic	no assertion criteria provided
872893	NM_001042475.3(CEP85L):c.232+5G>A	CEP85L	Pathogenic/Likely pathogenic	no assertion criteria provided
3027447	NM_001178035.2(CEP85L):c.57_60del (p.Ser20fs)	CEP85L	Likely pathogenic	criteria provided, single submitter
3064370	NM_001042475.3(CEP85L):c.2089C>T (p.Gln697Ter)	CEP85L	Likely pathogenic	criteria provided, single submitter
4291120	NM_001042475.3(CEP85L):c.232+5G>C	CEP85L	Likely pathogenic	criteria provided, single submitter
872890	NM_001042475.3(CEP85L):c.193G>A (p.Asp65Asn)	CEP85L	Likely pathogenic	criteria provided, single submitter
1406145	NM_001042475.3(CEP85L):c.173G>A (p.Ser58Asn)	CEP85L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
438602	NM_001042475.3(CEP85L):c.182C>T (p.Ser61Phe)	CEP85L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1325611	NM_001178035.2(CEP85L):c.7T>G (p.Trp3Gly)	CEP85L	Uncertain significance	criteria provided, single submitter
1328549	NM_001042475.3(CEP85L):c.442A>G (p.Lys148Glu)	CEP85L	Uncertain significance	criteria provided, single submitter
1709317	NM_001042475.3(CEP85L):c.452G>A (p.Arg151Gln)	CEP85L	Uncertain significance	criteria provided, multiple submitters, no conflicts
2439914	NM_001042475.3(CEP85L):c.2135T>C (p.Ile712Thr)	CEP85L	Uncertain significance	criteria provided, single submitter
2439915	NM_001042475.3(CEP85L):c.1103A>G (p.Glu368Gly)	CEP85L	Uncertain significance	criteria provided, single submitter
2439916	NM_001042475.3(CEP85L):c.1590+3A>T	CEP85L	Uncertain significance	criteria provided, single submitter
2439917	NM_001042475.3(CEP85L):c.1871_1874del (p.Asp624fs)	CEP85L	Uncertain significance	criteria provided, multiple submitters, no conflicts
2439918	NM_001042475.3(CEP85L):c.451del (p.Arg151fs)	CEP85L	Uncertain significance	criteria provided, single submitter
2439919	NM_001042475.3(CEP85L):c.34G>C (p.Gly12Arg)	CEP85L	Uncertain significance	criteria provided, single submitter
2664222	NM_001042475.3(CEP85L):c.1994T>C (p.Val665Ala)	CEP85L	Uncertain significance	criteria provided, single submitter
2671640	NM_001042475.3(CEP85L):c.1262A>C (p.Gln421Pro)	CEP85L	Uncertain significance	criteria provided, single submitter
3367051	NM_001042475.3(CEP85L):c.913C>T (p.Arg305Trp)	CEP85L	Uncertain significance	criteria provided, single submitter
3592997	NM_001042475.3(CEP85L):c.516C>T (p.Gly172=)	CEP85L	Uncertain significance	criteria provided, single submitter
3779052	NM_001042475.3(CEP85L):c.1522A>G (p.Ile508Val)	CEP85L	Uncertain significance	criteria provided, multiple submitters, no conflicts
4078249	NM_001042475.3(CEP85L):c.1528A>G (p.Thr510Ala)	CEP85L	Uncertain significance	criteria provided, single submitter
4846986	NM_001042475.3(CEP85L):c.1996C>T (p.Gln666Ter)	CEP85L	Uncertain significance	criteria provided, single submitter
1209726	NM_001042475.3(CEP85L):c.751C>A (p.Pro251Thr)	CEP85L	Benign	criteria provided, single submitter
1209727	NM_001042475.3(CEP85L):c.409A>G (p.Ser137Gly)	CEP85L	Benign	criteria provided, single submitter
1330390	NM_001042475.3(CEP85L):c.1020+17468G>A	CEP85L	Likely benign	criteria provided, multiple submitters, no conflicts
403328	NM_001042475.3(CEP85L):c.1020+17269T>G	CEP85L	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · 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
CEP85L	Definitive	Autosomal dominant	lissencephaly 10	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CEP85L	Orphanet:572013	Posterior-predominant lissencephaly-broad flat pons and medulla-midline crossing defects syndrome

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
CEP85L	HGNC:21638	ENSG00000111860	Q5SZL2	Centrosomal protein of 85 kDa-like	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CEP85L	Centrosomal protein of 85 kDa-like	Plays an essential role in neuronal cell migration.

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)
CEP85L	Other/Unknown	no		Cep85/Cep85L, CC4_CEP85

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
pylorus	1
thymus	1
tibialis anterior	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CEP85L	248	ubiquitous	marker	thymus, tibialis anterior, pylorus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CEP85L	581

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CEP85L	Q5SZL2	64.98

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
neuron migration	1	133.8×	0.007	CEP85L

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
CEP85L	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	CEP85L

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)
CEP85L	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.