Meier-Gorlin syndrome 7

Summary

Meier-Gorlin syndrome 7 (MONDO:0014894) is a disease caused by CDC45 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: CDC45 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 20

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Meier-Gorlin syndrome 7
Mondo ID	MONDO:0014894
OMIM	617063
DOID	DOID:0080518
UMLS	C4310738
MedGen	934705
GARD	0016181
Is cancer (heuristic)	no

Also known as: CDC45 Meier-Gorlin syndrome · Meier-Gorlin syndrome 7 · Meier-Gorlin syndrome 7; MGORS7 · Meier-Gorlin syndrome caused by mutation in CDC45 · Meier-Gorlin syndrome type 7 · MGORS7

Data availability: 20 ClinVar variants · 3 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 7

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 6, 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

20 retrieved; paginated sample, class counts are floors:

6 likely pathogenic, 5 uncertain significance, 4 pathogenic, 4 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1162262	NM_003504.5(CDC45):c.1445_1448del (p.Lys482fs)	CDC45	Pathogenic	no assertion criteria provided
253105	NM_003504.5(CDC45):c.(342+1_343-1)_(486+1_487-1)del	CDC45	Pathogenic	no assertion criteria provided
4525735	NM_003504.5(CDC45):c.1642G>T (p.Glu548Ter)	CDC45	Pathogenic	criteria provided, single submitter
617938	NM_003504.5(CDC45):c.1388C>T (p.Pro463Leu)	CDC45	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
619950	NM_003504.5(CDC45):c.326_329dup (p.Asn111fs)	CDC45	Pathogenic	criteria provided, multiple submitters, no conflicts
253097	NM_003504.5(CDC45):c.677A>G (p.Asp226Gly)	CDC45	Likely pathogenic	criteria provided, single submitter
253099	NM_003504.5(CDC45):c.226A>C (p.Asn76His)	CDC45	Likely pathogenic	criteria provided, single submitter
253102	NM_003504.5(CDC45):c.203A>G (p.Gln68Arg)	CDC45	Likely pathogenic	criteria provided, single submitter
253104	NM_003504.5(CDC45):c.893C>T (p.Ala298Val)	CDC45	Likely pathogenic	criteria provided, single submitter
3068440	NM_003504.5(CDC45):c.204G>A (p.Gln68=)	CDC45	Likely pathogenic	no assertion criteria provided
4849392	NM_003504.5(CDC45):c.1490del (p.Leu497fs)	CDC45	Likely pathogenic	criteria provided, single submitter
253100	NM_003504.5(CDC45):c.469C>T (p.Arg157Cys)	CDC45	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
253101	NM_003504.5(CDC45):c.1660C>T (p.Arg554Trp)	CDC45	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
635406	NM_003504.5(CDC45):c.1021C>T (p.Arg341Trp)	CDC45	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
872335	NM_003504.5(CDC45):c.1416C>T (p.His472=)	CDC45	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1033360	NM_003504.5(CDC45):c.1525A>G (p.Ile509Val)	CDC45	Uncertain significance	criteria provided, multiple submitters, no conflicts
253098	NM_003504.5(CDC45):c.318C>T (p.Val106=)	CDC45	Uncertain significance	criteria provided, single submitter
253103	NM_003504.5(CDC45):c.333C>T (p.Asn111=)	CDC45	Uncertain significance	criteria provided, single submitter
617920	NM_003504.5(CDC45):c.791C>A (p.Ser264Tyr)	CDC45	Uncertain significance	criteria provided, single submitter
617940	NM_003504.5(CDC45):c.1487C>T (p.Pro496Leu)	CDC45	Uncertain significance	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
CDC45	Definitive	Autosomal recessive	Meier-Gorlin syndrome 7	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CDC45	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
CDC45	HGNC:1739	ENSG00000093009	O75419	Cell division control protein 45 homolog	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CDC45	Cell division control protein 45 homolog	Required for initiation of chromosomal DNA replication.

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)
CDC45	Other/Unknown	no		CDC45

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
oocyte	1
right testis	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CDC45	172	ubiquitous	marker	oocyte, secondary oocyte, right testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CDC45	3,357

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CDC45	O75419	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 15. 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
DNA strand elongation	1	1142.0×	0.007	CDC45
Unwinding of DNA	1	878.5×	0.007	CDC45
G1/S-Specific Transcription	1	356.9×	0.007	CDC45
Activation of the pre-replicative complex	1	326.3×	0.007	CDC45
DNA Replication Pre-Initiation	1	317.2×	0.007	CDC45
Activation of ATR in response to replication stress	1	300.5×	0.007	CDC45
Synthesis of DNA	1	300.5×	0.007	CDC45
DNA Replication	1	237.9×	0.007	CDC45
G1/S Transition	1	233.1×	0.007	CDC45
Mitotic G1 phase and G1/S transition	1	184.2×	0.008	CDC45
S Phase	1	181.3×	0.008	CDC45
G2/M Checkpoints	1	134.3×	0.009	CDC45
Cell Cycle Checkpoints	1	88.5×	0.013	CDC45
Cell Cycle, Mitotic	1	48.2×	0.022	CDC45
Cell Cycle	1	36.0×	0.028	CDC45

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
mitotic DNA replication preinitiation complex assembly	1	16852.0×	3e-04	CDC45
DNA replication checkpoint signaling	1	1296.3×	0.001	CDC45
double-strand break repair via break-induced replication	1	1296.3×	0.001	CDC45
DNA replication initiation	1	624.1×	0.002	CDC45
DNA replication	1	165.2×	0.006	CDC45

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
CDC45	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	CDC45

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
CDC45	8	Binding: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

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	CDC45

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	CDC45
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.