Microcephaly 27, primary, autosomal dominant

Summary

Microcephaly 27, primary, autosomal dominant (MONDO:0030929) is a disease caused by LMNB2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: LMNB2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 13

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	microcephaly 27, primary, autosomal dominant
Mondo ID	MONDO:0030929
OMIM	619180
DOID	DOID:0051038
UMLS	C5543051
MedGen	1783457
GARD	0016433
Is cancer (heuristic)	no

Also known as: MCPH27 · microcephaly 27, primary, autosomal dominant

Data availability: 13 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › autosomal dominant primary microcephaly › microcephaly 27, primary, autosomal dominant

Related subtypes (2): microcephaly 26, primary, autosomal dominant, microcephaly 18, primary, autosomal dominant

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

13 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
3366973	NM_032737.4(LMNB2):c.578_579del (p.Val193fs)	LMNB2	Pathogenic	criteria provided, single submitter
997434	NM_032737.4(LMNB2):c.1192G>A (p.Glu398Lys)	LMNB2	Pathogenic	criteria provided, multiple submitters, no conflicts
997435	NM_032737.4(LMNB2):c.160A>C (p.Asn54His)	LMNB2	Pathogenic	no assertion criteria provided
2100666	NM_032737.4(LMNB2):c.1677C>G (p.Ser559Arg)	LMNB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
542437	NM_032737.4(LMNB2):c.574G>T (p.Ala192Ser)	LMNB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1489287	NM_032737.4(LMNB2):c.26G>A (p.Arg9His)	LMNB2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2578547	NM_032737.4(LMNB2):c.1163T>G (p.Ile388Ser)	LMNB2	Uncertain significance	criteria provided, single submitter
2582532	NM_032737.4(LMNB2):c.859G>A (p.Asp287Asn)	LMNB2	Uncertain significance	criteria provided, multiple submitters, no conflicts
3066095	NM_032737.4(LMNB2):c.889_891del (p.Asp297del)	LMNB2	Uncertain significance	criteria provided, single submitter
3891581	NM_032737.4(LMNB2):c.1760A>C (p.Glu587Ala)	LMNB2	Uncertain significance	criteria provided, single submitter
663575	NM_032737.4(LMNB2):c.802G>A (p.Asp268Asn)	LMNB2	Uncertain significance	criteria provided, multiple submitters, no conflicts
3731527	NM_032737.4(LMNB2):c.250G>A (p.Val84Met)	LOC130063065	Uncertain significance	criteria provided, single submitter
14474	NM_032737.4(LMNB2):c.704G>A (p.Arg235Gln)	LMNB2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 13 · Orphanet: 2 · 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
LMNB2	Strong	Autosomal dominant	microcephaly 27, primary, autosomal dominant	13

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LMNB2	Orphanet:457265	Progressive myoclonic epilepsy type 9
LMNB2	Orphanet:79087	Acquired partial lipodystrophy

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
LMNB2	HGNC:6638	ENSG00000176619	Q03252	Lamin-B2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LMNB2	Lamin-B2	Lamins are intermediate filament proteins that assemble into a filamentous meshwork, and which constitute the major components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane.

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)
LMNB2	Other/Unknown	no		Lamin_tail_dom, IF_conserved, Lamin_tail_dom_sf

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
left testis	1
right testis	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LMNB2	194	ubiquitous	marker	ventricular zone, left testis, right testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LMNB2	3,562

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
LMNB2	Q03252	2

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
nuclear pore localization	1	3370.4×	0.001	LMNB2
protein localization to nuclear envelope	1	2106.5×	0.001	LMNB2
nuclear envelope organization	1	991.3×	0.002	LMNB2
nuclear migration	1	732.7×	0.002	LMNB2
heterochromatin formation	1	255.3×	0.004	LMNB2

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
LMNB2	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
LMNB2	2	Binding:2

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	LMNB2

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)
LMNB2	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.