Meier-Gorlin syndrome 8

Summary

Meier-Gorlin syndrome 8 (MONDO:0033046) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Meier-Gorlin syndrome 8
Mondo ID	MONDO:0033046
OMIM	617564
DOID	DOID:0080255
UMLS	C4479655
MedGen	1390366
GARD	0025784
Is cancer (heuristic)	no

Also known as: Meier-Gorlin syndrome 8 · MGORS8

Data availability: 4 ClinVar variants · 2 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 8

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 7, 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

4 retrieved; paginated sample, class counts are floors:

2 uncertain significance, 1 benign, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
430637	NM_006739.4(MCM5):c.1397C>T (p.Thr466Ile)	MCM5	Pathogenic	no assertion criteria provided
1034303	NM_006739.4(MCM5):c.830C>A (p.Thr277Asn)	MCM5	Uncertain significance	criteria provided, multiple submitters, no conflicts
430636	NM_006739.4(MCM5):c.850_851del (p.Arg284fs)	MCM5	Uncertain significance	criteria provided, single submitter
1321159	NM_006739.4(MCM5):c.423+7C>T	MCM5	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 0 · 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
MCM5	Limited	Unknown	Meier-Gorlin syndrome 8	2

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
MCM5	HGNC:6948	ENSG00000100297	P33992	DNA replication licensing factor MCM5	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MCM5	DNA replication licensing factor MCM5	Acts as a component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for ‘once per cell cycle’ DNA replication initiation and elongation in eukaryotic cells.

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)
MCM5	Other/Unknown	no		MCM_dom, MCM5, NA-bd_OB-fold

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
MCM5	246	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
MCM5	4,221

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MCM5	P33992	27

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 21. 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
Regulation of MITF-M-dependent genes involved in DNA replication, damage repair and senescence	1	1631.4×	0.008	MCM5
DNA strand elongation	1	1142.0×	0.008	MCM5
Unwinding of DNA	1	878.5×	0.008	MCM5
Activation of the pre-replicative complex	1	326.3×	0.008	MCM5
DNA Replication Pre-Initiation	1	317.2×	0.008	MCM5
Activation of ATR in response to replication stress	1	300.5×	0.008	MCM5
Switching of origins to a post-replicative state	1	300.5×	0.008	MCM5
Synthesis of DNA	1	300.5×	0.008	MCM5
DNA Replication	1	237.9×	0.008	MCM5
G1/S Transition	1	233.1×	0.008	MCM5
Mitotic G1 phase and G1/S transition	1	184.2×	0.008	MCM5
S Phase	1	181.3×	0.008	MCM5
MITF-M-dependent gene expression	1	181.3×	0.008	MCM5
Orc1 removal from chromatin	1	178.4×	0.008	MCM5
Assembly of the pre-replicative complex	1	139.3×	0.010	MCM5
G2/M Checkpoints	1	134.3×	0.010	MCM5
MITF-M-regulated melanocyte development	1	114.2×	0.011	MCM5
Cell Cycle Checkpoints	1	88.5×	0.013	MCM5
Cell Cycle, Mitotic	1	48.2×	0.023	MCM5
Cell Cycle	1	36.0×	0.029	MCM5
Developmental Biology	1	14.5×	0.069	MCM5

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
double-strand break repair via break-induced replication	1	1296.3×	0.002	MCM5
regulation of DNA-templated DNA replication initiation	1	1053.2×	0.002	MCM5
DNA replication initiation	1	624.1×	0.002	MCM5
DNA replication	1	165.2×	0.006	MCM5

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
MCM5	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
MCM5	10	Binding:10

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	MCM5

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)
MCM5	10	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.