Meier-Gorlin syndrome 4

Summary

Meier-Gorlin syndrome 4 (MONDO:0013431) is a disease caused by CDT1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: CDT1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 30

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Meier-Gorlin syndrome 4
Mondo ID	MONDO:0013431
OMIM	613804
DOID	DOID:0080515
UMLS	C3151120
MedGen	462470
GARD	0015711
Is cancer (heuristic)	no

Also known as: CDT1 Meier-Gorlin syndrome · Meier-Gorlin syndrome 4 · Meier-Gorlin syndrome caused by mutation in CDT1 · Meier-Gorlin syndrome type 4 · MGORS4

Data availability: 30 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 4

Related subtypes (9): Meier-Gorlin syndrome 1, Meier-Gorlin syndrome 2, Meier-Gorlin syndrome 3, Meier-Gorlin syndrome 5, 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

30 retrieved; paginated sample, class counts are floors:

7 uncertain significance, 6 pathogenic, 5 conflicting classifications of pathogenicity, 4 benign, 3 likely pathogenic, 2 pathogenic/likely pathogenic, 1 not provided, 1 benign/likely benign, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1173055	NM_030928.4(CDT1):c.1078_1080del (p.Ala360del)	CDT1	Pathogenic	criteria provided, single submitter
1173056	NM_030928.4(CDT1):c.1276-24A>G	CDT1	Pathogenic	criteria provided, single submitter
128664	NM_030928.4(CDT1):c.832+1G>A	CDT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2503832	NM_030928.4(CDT1):c.166_167delinsA (p.Ala56fs)	CDT1	Pathogenic	criteria provided, single submitter
30498	NM_030928.4(CDT1):c.1385G>A (p.Arg462Gln)	CDT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
30499	NM_030928.4(CDT1):c.1560C>G (p.Tyr520Ter)	CDT1	Pathogenic	no assertion criteria provided
30500	NM_030928.4(CDT1):c.351G>C (p.Gln117His)	CDT1	Pathogenic	no assertion criteria provided
30501	NM_030928.4(CDT1):c.196G>A (p.Ala66Thr)	CDT1	Pathogenic	no assertion criteria provided
1324040	NM_030928.4(CDT1):c.802C>T (p.Gln268Ter)	CDT1	Likely pathogenic	criteria provided, single submitter
2431870	NM_030928.4(CDT1):c.652A>T (p.Lys218Ter)	CDT1	Likely pathogenic	criteria provided, single submitter
4849302	NM_030928.4(CDT1):c.162_163insTCCC (p.Ala55fs)	CDT1	Likely pathogenic	criteria provided, single submitter
1495760	NM_030928.4(CDT1):c.1234C>A (p.Pro412Thr)	CDT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
210649	NM_030928.4(CDT1):c.1411C>G (p.Pro471Ala)	CDT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
30502	NM_030928.4(CDT1):c.1402G>A (p.Glu468Lys)	CDT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
434673	NM_030928.4(CDT1):c.613G>A (p.Gly205Ser)	CDT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
434677	NM_030928.4(CDT1):c.1357C>T (p.Arg453Trp)	CDT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1029984	NM_030928.4(CDT1):c.1125G>A (p.Met375Ile)	CDT1	Uncertain significance	criteria provided, single submitter
1421268	NM_030928.4(CDT1):c.841G>A (p.Gly281Arg)	CDT1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1469510	NM_030928.4(CDT1):c.748C>T (p.Arg250Cys)	CDT1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2439891	NM_030928.4(CDT1):c.260A>G (p.Asp87Gly)	CDT1	Uncertain significance	criteria provided, single submitter
3064758	NM_030928.4(CDT1):c.610G>A (p.Val204Met)	CDT1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3065541	NM_030928.4(CDT1):c.1381C>A (p.Leu461Met)	CDT1	Uncertain significance	criteria provided, single submitter
3581336	NM_030928.4(CDT1):c.352-7C>G	CDT1	Uncertain significance	criteria provided, single submitter
128673	NM_030928.4(CDT1):c.1587C>G (p.Leu529=)	CDT1	Benign	criteria provided, multiple submitters, no conflicts
128680	NM_030928.4(CDT1):c.700T>C (p.Cys234Arg)	CDT1	Benign	criteria provided, multiple submitters, no conflicts
128682	NM_030928.4(CDT1):c.784A>G (p.Thr262Ala)	CDT1	Benign	criteria provided, multiple submitters, no conflicts
128683	NM_030928.4(CDT1):c.915T>C (p.His305=)	CDT1	Benign	criteria provided, multiple submitters, no conflicts
790427	NM_030928.4(CDT1):c.248C>T (p.Pro83Leu)	CDT1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
799874	NM_030928.4(CDT1):c.999G>A (p.Pro333=)	CDT1	Likely benign	criteria provided, multiple submitters, no conflicts
441024	NM_030928.4(CDT1):c.1154G>A (p.Arg385His)	CDT1	not provided	no classification provided

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
CDT1	Definitive	Autosomal recessive	Meier-Gorlin syndrome 4	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CDT1	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
CDT1	HGNC:24576	ENSG00000167513	Q9H211	DNA replication factor Cdt1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CDT1	DNA replication factor Cdt1	Required for both DNA replication and mitosis.

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)
CDT1	Other/Unknown	no		CDT1_Gemini-bd-like, Cdt1_C, WH_DNA-bd_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
mucosa of paranasal sinus	1
oocyte	1
superficial temporal artery	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CDT1	185	ubiquitous	marker	mucosa of paranasal sinus, superficial temporal artery, oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CDT1	2,813

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CDT1	Q9H211	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. 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
G1/S-Specific Transcription	1	356.9×	0.007	CDT1
Activation of the pre-replicative complex	1	326.3×	0.007	CDT1
DNA Replication Pre-Initiation	1	317.2×	0.007	CDT1
Switching of origins to a post-replicative state	1	300.5×	0.007	CDT1
Synthesis of DNA	1	300.5×	0.007	CDT1
DNA Replication	1	237.9×	0.007	CDT1
G1/S Transition	1	233.1×	0.007	CDT1
Mitotic G1 phase and G1/S transition	1	184.2×	0.007	CDT1
S Phase	1	181.3×	0.007	CDT1
Orc1 removal from chromatin	1	178.4×	0.007	CDT1
Assembly of the pre-replicative complex	1	139.3×	0.008	CDT1
Cell Cycle, Mitotic	1	48.2×	0.022	CDT1
Cell Cycle	1	36.0×	0.028	CDT1

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
DNA replication preinitiation complex assembly	1	16852.0×	4e-04	CDT1
mitotic pre-replicative complex assembly	1	16852.0×	4e-04	CDT1
response to sorbitol	1	8426.0×	5e-04	CDT1
negative regulation of DNA-templated DNA replication	1	5617.3×	6e-04	CDT1
regulation of nuclear cell cycle DNA replication	1	3370.4×	8e-04	CDT1
mitotic DNA replication initiation	1	2808.7×	8e-04	CDT1
DNA replication checkpoint signaling	1	1296.3×	0.001	CDT1
regulation of DNA-templated DNA replication initiation	1	1053.2×	0.001	CDT1
attachment of mitotic spindle microtubules to kinetochore	1	1053.2×	0.001	CDT1
positive regulation of DNA replication	1	581.1×	0.002	CDT1
negative regulation of cell cycle	1	290.6×	0.004	CDT1
mitotic cell cycle	1	133.8×	0.008	CDT1
cell division	1	46.2×	0.022	CDT1

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CDT1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	CDT1

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)
CDT1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.