Microcephaly 26, primary, autosomal dominant

Summary

Microcephaly 26, primary, autosomal dominant (MONDO:0030928) is a disease caused by LMNB1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: LMNB1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 15

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	microcephaly 26, primary, autosomal dominant
Mondo ID	MONDO:0030928
OMIM	619179
DOID	DOID:0051037
UMLS	C5543048
MedGen	1779629
GARD	0016432
Is cancer (heuristic)	no

Also known as: MCPH26 · microcephaly 26, primary, autosomal dominant

Data availability: 15 ClinVar variants · 3 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 26, primary, autosomal dominant

Related subtypes (2): microcephaly 27, 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

15 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 5 pathogenic, 2 likely pathogenic, 1 benign/likely benign, 1 conflicting classifications of pathogenicity, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
915454	NM_005573.4(LMNB1):c.455C>G (p.Ala152Gly)	LMNB1	Pathogenic	no assertion criteria provided
915455	NM_005573.4(LMNB1):c.97A>G (p.Lys33Glu)	LMNB1	Pathogenic	criteria provided, multiple submitters, no conflicts
915456	NM_005573.4(LMNB1):c.124C>T (p.Arg42Trp)	LMNB1	Pathogenic	criteria provided, multiple submitters, no conflicts
915457	NM_005573.4(LMNB1):c.939+1G>A	LMNB1	Pathogenic	criteria provided, single submitter
915458	NM_005573.4(LMNB1):c.939+2362_1491+560del	LMNB1	Pathogenic	no assertion criteria provided
2444231	NM_005573.4(LMNB1):c.814-1G>T	LMNB1	Likely pathogenic	criteria provided, single submitter
997433	NM_005573.4(LMNB1):c.269G>C (p.Arg90Pro)	LMNB1	Likely pathogenic	criteria provided, single submitter
1366654	NM_005573.4(LMNB1):c.1306G>A (p.Ala436Thr)	LMNB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1339183	NM_005573.4(LMNB1):c.1138C>T (p.Leu380Phe)	LMNB1	Uncertain significance	criteria provided, single submitter
2599057	NM_005573.4(LMNB1):c.1361T>C (p.Ile454Thr)	LMNB1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3234997	NM_005573.4(LMNB1):c.382C>G (p.Leu128Val)	LMNB1	Uncertain significance	criteria provided, single submitter
3254809	NM_005573.4(LMNB1):c.1283G>C (p.Ser428Thr)	LMNB1	Uncertain significance	criteria provided, single submitter
4845354	NM_005573.4(LMNB1):c.1118A>T (p.Glu373Val)	LMNB1	Uncertain significance	criteria provided, single submitter
1170530	NM_005573.4(LMNB1):c.360-19C>T	LMNB1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
2443339	NM_005573.4(LMNB1):c.455C>T (p.Ala152Val)	LMNB1	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · 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
LMNB1	Definitive	Autosomal dominant	microcephaly 26, primary, autosomal dominant	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LMNB1	Orphanet:2514	Autosomal dominant primary microcephaly
LMNB1	Orphanet:99027	Adult-onset autosomal dominant leukodystrophy

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
LMNB1	HGNC:6637	ENSG00000113368	P20700	Lamin-B1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LMNB1	Lamin-B1	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)
LMNB1	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
embryo	1
ganglionic eminence	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LMNB1	226	ubiquitous	marker	ventricular zone, ganglionic eminence, embryo

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LMNB1	5,226

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
LMNB1	P20700	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 40. 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
Breakdown of the nuclear lamina	1	3806.7×	0.007	LMNB1
Neurodegenerative Diseases	1	878.5×	0.007	LMNB1
Depolymerization of the Nuclear Lamina	1	761.3×	0.007	LMNB1
Defective Intrinsic Pathway for Apoptosis	1	761.3×	0.007	LMNB1
Formation of Senescence-Associated Heterochromatin Foci (SAHF)	1	671.8×	0.007	LMNB1
Diseases of programmed cell death	1	634.4×	0.007	LMNB1
Initiation of Nuclear Envelope (NE) Reformation	1	601.0×	0.007	LMNB1
Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer’s disease models	1	519.1×	0.007	LMNB1
Apoptotic cleavage of cellular proteins	1	475.8×	0.007	LMNB1
Interleukin-12 family signaling	1	475.8×	0.007	LMNB1
Apoptotic execution phase	1	475.8×	0.007	LMNB1
Nuclear Envelope Breakdown	1	456.8×	0.007	LMNB1
Interleukin-12 signaling	1	407.9×	0.008	LMNB1
Mitotic Prophase	1	368.4×	0.008	LMNB1
Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation	1	300.5×	0.008	LMNB1
Nuclear Envelope (NE) Reassembly	1	292.8×	0.008	LMNB1
Meiosis	1	285.5×	0.008	LMNB1
RHOF GTPase cycle	1	259.6×	0.009	LMNB1
RHOD GTPase cycle	1	203.9×	0.010	LMNB1
Reproduction	1	190.3×	0.011	LMNB1
Apoptosis	1	167.9×	0.011	LMNB1
DNA Damage/Telomere Stress Induced Senescence	1	163.1×	0.011	LMNB1
Programmed Cell Death	1	146.4×	0.012	LMNB1
Meiotic synapsis	1	141.0×	0.012	LMNB1
Cellular Senescence	1	137.6×	0.012	LMNB1
Mitotic Metaphase and Anaphase	1	96.8×	0.015	LMNB1
Mitotic Anaphase	1	96.8×	0.015	LMNB1
M Phase	1	66.0×	0.021	LMNB1
Signaling by Interleukins	1	64.2×	0.021	LMNB1
RHO GTPase cycle	1	60.1×	0.022	LMNB1

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	LMNB1
protein localization to nuclear envelope	1	2106.5×	0.001	LMNB1
nuclear envelope organization	1	991.3×	0.002	LMNB1
nuclear migration	1	732.7×	0.002	LMNB1
heterochromatin formation	1	255.3×	0.004	LMNB1

Therapeutics

Drug target analysis

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

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
LMNB1	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	LMNB1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
LMNB1	7	Binding:7

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

1 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.

Compound	Max phase	Cohort target (bioactivity)
MOLIBRESIB	2	LMNB1

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	1	LMNB1
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.