Meier-Gorlin syndrome 5

Summary

Meier-Gorlin syndrome 5 (MONDO:0013432) is a disease caused by CDC6 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: CDC6 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 34

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Meier-Gorlin syndrome 5
Mondo ID	MONDO:0013432
OMIM	613805
DOID	DOID:0080516
UMLS	C3151126
MedGen	462476
GARD	0015712
Is cancer (heuristic)	no

Also known as: CDC6 Meier-Gorlin syndrome · Meier-Gorlin syndrome 5 · Meier-Gorlin syndrome caused by mutation in CDC6 · Meier-Gorlin syndrome type 5 · MGORS5

Data availability: 34 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 5

Related subtypes (9): Meier-Gorlin syndrome 1, Meier-Gorlin syndrome 2, Meier-Gorlin syndrome 3, Meier-Gorlin syndrome 4, Meier-Gorlin syndrome 6, 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

34 retrieved; paginated sample, class counts are floors:

16 uncertain significance, 6 conflicting classifications of pathogenicity, 5 benign, 3 no classifications from unflagged records, 3 likely benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
210621	NM_001254.4(CDC6):c.712A>G (p.Thr238Ala)	CDC6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
323056	NM_001254.4(CDC6):c.799T>C (p.Leu267=)	CDC6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
323058	NM_001254.4(CDC6):c.1020G>A (p.Leu340=)	CDC6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
434626	NM_001254.4(CDC6):c.897G>A (p.Thr299=)	CDC6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
889772	NM_001254.4(CDC6):c.1184+10G>A	CDC6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
892451	NM_001254.4(CDC6):c.179-14T>C	CDC6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
30271	NM_001254.4(CDC6):c.968C>G (p.Thr323Arg)	CDC6	no classifications from unflagged records	no classifications from unflagged records
323051	NM_001254.4(CDC6):c.-36T>G	CDC6	Uncertain significance	criteria provided, single submitter
323052	NM_001254.4(CDC6):c.-14+8G>C	CDC6	Uncertain significance	criteria provided, single submitter
323054	NM_001254.4(CDC6):c.464C>T (p.Thr155Ile)	CDC6	Uncertain significance	criteria provided, single submitter
323057	NM_001254.4(CDC6):c.845T>C (p.Val282Ala)	CDC6	Uncertain significance	criteria provided, multiple submitters, no conflicts
323061	NM_001254.4(CDC6):c.*181A>G	CDC6	Uncertain significance	criteria provided, single submitter
323062	NM_001254.4(CDC6):c.*353T>G	CDC6	Uncertain significance	criteria provided, single submitter
323065	NM_001254.4(CDC6):c.*414C>T	CDC6	Uncertain significance	criteria provided, single submitter
323068	NM_001254.4(CDC6):c.*747G>A	CDC6	Uncertain significance	criteria provided, single submitter
3600315	NM_001254.4(CDC6):c.230A>G (p.Lys77Arg)	CDC6	no classifications from unflagged records	no classifications from unflagged records
3600316	NM_001254.4(CDC6):c.232C>T (p.Gln78Ter)	CDC6	no classifications from unflagged records	no classifications from unflagged records
889072	NM_001254.4(CDC6):c.508G>A (p.Asp170Asn)	CDC6	Uncertain significance	criteria provided, single submitter
889073	NM_001254.4(CDC6):c.894C>T (p.Tyr298=)	CDC6	Uncertain significance	criteria provided, single submitter
889770	NM_001254.4(CDC6):c.1084-15A>G	CDC6	Uncertain significance	criteria provided, single submitter
889771	NM_001254.4(CDC6):c.1133G>A (p.Arg378His)	CDC6	Uncertain significance	criteria provided, multiple submitters, no conflicts
889773	NM_001254.4(CDC6):c.1591A>G (p.Lys531Glu)	CDC6	Uncertain significance	criteria provided, multiple submitters, no conflicts
891308	NM_001254.4(CDC6):c.*84G>A	CDC6	Uncertain significance	criteria provided, single submitter
891309	NM_001254.4(CDC6):c.*635G>T	CDC6	Uncertain significance	criteria provided, single submitter
892450	NM_001254.4(CDC6):c.129C>T (p.Thr43=)	CDC6	Uncertain significance	criteria provided, single submitter
128635	NM_001254.4(CDC6):c.1321G>A (p.Val441Ile)	CDC6	Benign	criteria provided, multiple submitters, no conflicts
128636	NM_001254.4(CDC6):c.438T>C (p.Cys146=)	CDC6	Benign	criteria provided, multiple submitters, no conflicts
128638	NM_001254.4(CDC6):c.883G>A (p.Asp295Asn)	CDC6	Benign	criteria provided, multiple submitters, no conflicts
128639	NM_001254.4(CDC6):c.896C>T (p.Thr299Met)	CDC6	Benign	criteria provided, multiple submitters, no conflicts
210619	NM_001254.4(CDC6):c.165C>T (p.Pro55=)	CDC6	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

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
CDC6	Definitive	Autosomal recessive	Meier-Gorlin syndrome 5	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CDC6	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
CDC6	HGNC:1744	ENSG00000094804	Q99741	Cell division control protein 6 homolog	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CDC6	Cell division control protein 6 homolog	Involved in the initiation of 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)
CDC6	Other/Unknown	no		AAA+_ATPase, Cdc6_C, Cdc6/18

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
CDC6	186	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
CDC6	3,877

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CDC6	Q99741	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 20. 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
CDC6 association with the ORC:origin complex	1	1427.5×	0.007	CDC6
Transcription of E2F targets under negative control by DREAM complex	1	543.8×	0.007	CDC6
G0 and Early G1	1	439.2×	0.007	CDC6
G1/S-Specific Transcription	1	356.9×	0.007	CDC6
Activation of the pre-replicative complex	1	326.3×	0.007	CDC6
DNA Replication Pre-Initiation	1	317.2×	0.007	CDC6
Activation of ATR in response to replication stress	1	300.5×	0.007	CDC6
Switching of origins to a post-replicative state	1	300.5×	0.007	CDC6
Synthesis of DNA	1	300.5×	0.007	CDC6
DNA Replication	1	237.9×	0.008	CDC6
G1/S Transition	1	233.1×	0.008	CDC6
Mitotic G1 phase and G1/S transition	1	184.2×	0.008	CDC6
S Phase	1	181.3×	0.008	CDC6
Orc1 removal from chromatin	1	178.4×	0.008	CDC6
CDK-mediated phosphorylation and removal of Cdc6	1	170.4×	0.008	CDC6
Assembly of the pre-replicative complex	1	139.3×	0.009	CDC6
G2/M Checkpoints	1	134.3×	0.009	CDC6
Cell Cycle Checkpoints	1	88.5×	0.013	CDC6
Cell Cycle, Mitotic	1	48.2×	0.022	CDC6
Cell Cycle	1	36.0×	0.028	CDC6

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
traversing start control point of mitotic cell cycle	1	4213.0×	0.002	CDC6
cellular response to vasopressin	1	2106.5×	0.002	CDC6
mitotic DNA replication checkpoint signaling	1	1532.0×	0.002	CDC6
DNA replication checkpoint signaling	1	1296.3×	0.002	CDC6
positive regulation of chromosome segregation	1	1296.3×	0.002	CDC6
cellular response to angiotensin	1	936.2×	0.002	CDC6
negative regulation of DNA replication	1	887.0×	0.002	CDC6
regulation of cyclin-dependent protein serine/threonine kinase activity	1	732.7×	0.002	CDC6
DNA replication initiation	1	624.1×	0.002	CDC6
regulation of mitotic metaphase/anaphase transition	1	495.6×	0.003	CDC6
positive regulation of cytokinesis	1	401.2×	0.003	CDC6
positive regulation of fibroblast proliferation	1	295.6×	0.004	CDC6
cell division	1	46.2×	0.023	CDC6
negative regulation of cell population proliferation	1	42.1×	0.024	CDC6

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
CDC6	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
CDC6	1	Binding:1

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	CDC6

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)
CDC6	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.