Meier-Gorlin syndrome 6

Summary

Meier-Gorlin syndrome 6 (MONDO:0014794) is a disease caused by GMNN (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: GMNN (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 8

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Meier-Gorlin syndrome 6
Mondo ID	MONDO:0014794
OMIM	616835
DOID	DOID:0080517
UMLS	C4225188
MedGen	905079
GARD	0016163
Is cancer (heuristic)	no

Also known as: GMNN Meier-Gorlin syndrome · Meier-Gorlin syndrome 6 · Meier-Gorlin syndrome caused by mutation in GMNN · Meier-Gorlin syndrome type 6 · MGORS6

Data availability: 8 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Meier-Gorlin syndrome › Meier-Gorlin syndrome 6

Related subtypes (9): Meier-Gorlin syndrome 1, Meier-Gorlin syndrome 2, Meier-Gorlin syndrome 3, Meier-Gorlin syndrome 4, Meier-Gorlin syndrome 5, Meier-Gorlin syndrome 7, Meier-Gorlin syndrome 8, Meier-Gorlin syndrome 9, Meier-Gorlin syndrome 10

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

8 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 2 pathogenic, 1 conflicting classifications of pathogenicity, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
203999	NM_015895.5(GMNN):c.16A>T (p.Lys6Ter)	GMNN	Pathogenic	criteria provided, single submitter
204000	NM_015895.5(GMNN):c.35_38del (p.Ile12fs)	GMNN	Pathogenic	criteria provided, single submitter
204001	NM_015895.5(GMNN):c.50A>G (p.Lys17Arg)	GMNN	Likely pathogenic	criteria provided, single submitter
1006625	NM_015895.5(GMNN):c.64C>T (p.Pro22Ser)	GMNN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1333989	NM_015895.5(GMNN):c.276A>G (p.Glu92=)	GMNN	Uncertain significance	criteria provided, single submitter
3382999	NM_015895.5(GMNN):c.541_542del (p.Thr180_Val181insTer)	GMNN	Uncertain significance	criteria provided, single submitter
3779703	NM_015895.5(GMNN):c.596dup (p.Ser200fs)	GMNN	Uncertain significance	criteria provided, single submitter
4056499	NM_015895.5(GMNN):c.568_569del (p.Glu190fs)	GMNN	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
GMNN	Strong	Autosomal dominant	Meier-Gorlin syndrome 6	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GMNN	Orphanet:2554	Ear-patella-short stature 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
GMNN	HGNC:17493	ENSG00000112312	O75496	Geminin	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GMNN	Geminin	Inhibits DNA replication by preventing the incorporation of MCM complex into pre-replication complex (pre-RC).

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)
GMNN	Other/Unknown	no		Geminin/Multicilin

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
body of pancreas	1
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GMNN	280	ubiquitous	marker	oocyte, body of pancreas, secondary oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GMNN	2,074

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GMNN	O75496	6

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
Activation of the pre-replicative complex	1	326.3×	0.005	GMNN
Switching of origins to a post-replicative state	1	300.5×	0.005	GMNN
Assembly of the pre-replicative complex	1	139.3×	0.007	GMNN

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
negative regulation of mitotic DNA replication initiation	1	8426.0×	9e-04	GMNN
negative regulation of DNA-templated DNA replication	1	5617.3×	9e-04	GMNN
regulation of DNA-templated DNA replication initiation	1	1053.2×	0.003	GMNN
negative regulation of DNA replication	1	887.0×	0.003	GMNN
regulation of DNA replication	1	366.4×	0.005	GMNN
negative regulation of cell cycle	1	290.6×	0.006	GMNN
regulation of mitotic cell cycle	1	240.7×	0.006	GMNN
animal organ morphogenesis	1	191.5×	0.007	GMNN
protein-containing complex assembly	1	113.9×	0.010	GMNN
negative regulation of DNA-templated transcription	1	31.6×	0.032	GMNN

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · 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).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
GMNN	CLOTRIMAZOLE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GMNN	82	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CLOTRIMAZOLE	4	GMNN
COLCHICINE	4	GMNN
SALMETEROL XINAFOATE	4	GMNN
AMIODARONE HYDROCHLORIDE	4	GMNN
RALOXIFENE HYDROCHLORIDE	4	GMNN
IDARUBICIN	4	GMNN
NICARDIPINE HYDROCHLORIDE	4	GMNN
DOBUTAMINE HYDROCHLORIDE	4	GMNN
GUANFACINE HYDROCHLORIDE	4	GMNN
BROMOCRIPTINE MESYLATE	4	GMNN
DIHYDROERGOTAMINE MESYLATE	4	GMNN
DOXAZOSIN MESYLATE	4	GMNN
PROMETHAZINE HYDROCHLORIDE	4	GMNN
THIORIDAZINE HYDROCHLORIDE	4	GMNN
FLUOXETINE HYDROCHLORIDE	4	GMNN
TRIFLUPROMAZINE HYDROCHLORIDE	4	GMNN
DEQUALINIUM CHLORIDE	4	GMNN
TETRACAINE HYDROCHLORIDE	4	GMNN
MIFEPRISTONE	4	GMNN
PROCHLORPERAZINE MALEATE	4	GMNN
MITOXANTRONE HYDROCHLORIDE	4	GMNN
PIMOZIDE	4	GMNN
NICLOSAMIDE	4	GMNN
FLUPHENAZINE HYDROCHLORIDE	4	GMNN
FELODIPINE	4	GMNN
AZACITIDINE	4	GMNN
EPHEDRINE SULFATE	4	GMNN
PIRENZEPINE HYDROCHLORIDE	4	GMNN
MIBEFRADIL DIHYDROCHLORIDE	4	GMNN
AZATHIOPRINE	4	GMNN

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
GMNN	8	Functional:8

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

30 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)
CLOTRIMAZOLE	4	GMNN
COLCHICINE	4	GMNN
SALMETEROL XINAFOATE	4	GMNN
AMIODARONE HYDROCHLORIDE	4	GMNN
RALOXIFENE HYDROCHLORIDE	4	GMNN
IDARUBICIN	4	GMNN
NICARDIPINE HYDROCHLORIDE	4	GMNN
DOBUTAMINE HYDROCHLORIDE	4	GMNN
GUANFACINE HYDROCHLORIDE	4	GMNN
BROMOCRIPTINE MESYLATE	4	GMNN
DIHYDROERGOTAMINE MESYLATE	4	GMNN
DOXAZOSIN MESYLATE	4	GMNN
PROMETHAZINE HYDROCHLORIDE	4	GMNN
THIORIDAZINE HYDROCHLORIDE	4	GMNN
FLUOXETINE HYDROCHLORIDE	4	GMNN
TRIFLUPROMAZINE HYDROCHLORIDE	4	GMNN
DEQUALINIUM CHLORIDE	4	GMNN
TETRACAINE HYDROCHLORIDE	4	GMNN
MIFEPRISTONE	4	GMNN
PROCHLORPERAZINE MALEATE	4	GMNN
MITOXANTRONE HYDROCHLORIDE	4	GMNN
PIMOZIDE	4	GMNN
NICLOSAMIDE	4	GMNN
FLUPHENAZINE HYDROCHLORIDE	4	GMNN
FELODIPINE	4	GMNN
AZACITIDINE	4	GMNN
EPHEDRINE SULFATE	4	GMNN
PIRENZEPINE HYDROCHLORIDE	4	GMNN
MIBEFRADIL DIHYDROCHLORIDE	4	GMNN
AZATHIOPRINE	4	GMNN

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	GMNN
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	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.