Microcephaly, progressive, with simplified gyral pattern and cerebellar hypoplasia

disease

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Summary

Microcephaly, progressive, with simplified gyral pattern and cerebellar hypoplasia (MONDO:0980935) is a disease with 1 cohort gene.

At a glance

Cohort genes: 1
ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	microcephaly, progressive, with simplified gyral pattern and cerebellar hypoplasia
Mondo ID	MONDO:0980935
OMIM	621436
Is cancer (heuristic)	no

Data availability: 4 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › disorder of development or morphogenesis › microcephaly › microcephaly, progressive, with simplified gyral pattern and cerebellar hypoplasia

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:

3 pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
4538465	NM_001278628.2(CRNKL1):c.317G>A (p.Arg106His)	CRNKL1	Pathogenic	no assertion criteria provided
4538466	NM_001278628.2(CRNKL1):c.316C>T (p.Arg106Cys)	CRNKL1	Pathogenic	no assertion criteria provided
4538467	NM_001278628.2(CRNKL1):c.418C>G (p.Arg140Gly)	CRNKL1	Pathogenic	no assertion criteria provided
4819442	NM_001278628.2(CRNKL1):c.51+2T>C	CRNKL1	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

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

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
CRNKL1	HGNC:15762	ENSG00000101343	Q9BZJ0	Crooked neck-like protein 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CRNKL1	Crooked neck-like protein 1	Involved in pre-mRNA splicing process.

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)
CRNKL1	Other/Unknown	no		HAT, TPR-like_helical_dom_sf, Syf1-like

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
calcaneal tendon	1
ganglionic eminence	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CRNKL1	278	ubiquitous	marker	calcaneal tendon, ventricular zone, ganglionic eminence

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CRNKL1	3,228

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CRNKL1	Q9BZJ0	31

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
mRNA Splicing - Major Pathway	1	54.6×	0.022	CRNKL1
Dengue Virus-Host Interactions	1	45.7×	0.022	CRNKL1

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
spliceosomal complex assembly	1	601.9×	0.003	CRNKL1
mRNA splicing, via spliceosome	1	91.6×	0.011	CRNKL1

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
CRNKL1	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	CRNKL1

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)
CRNKL1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: CRNKL1