Monosomy 7 myelodysplasia and leukemia syndrome 1

Summary

Monosomy 7 myelodysplasia and leukemia syndrome 1 (MONDO:0009646) is a cancer with 3 cohort genes.

At a glance

• Classification: Cancer
• Cohort genes: 3
• ClinVar variants: 46

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	monosomy 7 myelodysplasia and leukemia syndrome 1
Mondo ID	MONDO:0009646
MeSH	C565370
OMIM	252270
NCIT	C176908
UMLS	C1854978
MedGen	381529
GARD	0018505
Is cancer (heuristic)	yes

Also known as: chromosome 7Q deletion · M7MLS1 · monosomy 7 of bone marrow · myelodysplasia and leukaemia syndrome with monosomy 7 · myelodysplasia and leukemia syndrome with monosomy 7

Data availability: 46 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › familial monosomy 7 syndrome › monosomy 7 myelodysplasia and leukemia syndrome 1

Related subtypes (1): monosomy 7 myelodysplasia and leukemia syndrome 2

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

46 retrieved; paginated sample, class counts are floors:

23 uncertain significance, 11 conflicting classifications of pathogenicity, 5 benign/likely benign, 3 likely pathogenic, 2 pathogenic, 1 benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
242372	NM_152703.5(SAMD9L):c.2640C>A (p.His880Gln)	SAMD9L	Pathogenic	criteria provided, single submitter
446530	NM_152703.5(SAMD9L):c.2956C>T (p.Arg986Cys)	SAMD9L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
988631	NM_152703.5(SAMD9L):c.3842G>A (p.Arg1281Lys)	SAMD9L	Pathogenic	no assertion criteria provided
1320284	NM_152703.5(SAMD9L):c.4654T>A (p.Tyr1552Asn)	SAMD9L	Likely pathogenic	criteria provided, single submitter
1333474	NM_152703.5(SAMD9L):c.303del (p.Asn103fs)	SAMD9L	Likely pathogenic	criteria provided, single submitter
3382574	NM_152703.5(SAMD9L):c.2675T>G (p.Met892Arg)	SAMD9L	Likely pathogenic	criteria provided, single submitter
1017243	NM_152703.5(SAMD9L):c.4082T>C (p.Val1361Ala)	SAMD9L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1038336	NM_152703.5(SAMD9L):c.1549T>C (p.Trp517Arg)	SAMD9L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1049582	NM_152703.5(SAMD9L):c.2069G>A (p.Gly690Asp)	SAMD9L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1049620	NM_152703.5(SAMD9L):c.2528G>A (p.Arg843Gln)	SAMD9L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1063306	NM_152703.5(SAMD9L):c.854G>A (p.Arg285Gln)	SAMD9L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1519066	NM_152703.5(SAMD9L):c.4298T>C (p.Leu1433Pro)	SAMD9L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1520277	NM_152703.5(SAMD9L):c.4646T>C (p.Ile1549Thr)	SAMD9L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
432926	NM_152703.5(SAMD9L):c.1877C>T (p.Ser626Leu)	SAMD9L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
774190	NM_152703.5(SAMD9L):c.1216C>T (p.Arg406Ter)	SAMD9L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
813694	NM_152703.5(SAMD9L):c.2114A>G (p.Tyr705Cys)	SAMD9L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
886156	NM_001039.4(SCNN1G):c.1861G>A (p.Gly621Ser)	SCNN1G	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1015386	NM_152703.5(SAMD9L):c.3568G>C (p.Asp1190His)	SAMD9L	Uncertain significance	criteria provided, multiple submitters, no conflicts
1316334	NM_152703.5(SAMD9L):c.1934T>A (p.Leu645Gln)	SAMD9L	Uncertain significance	criteria provided, multiple submitters, no conflicts
1320750	NM_152703.5(SAMD9L):c.987del (p.Asp330fs)	SAMD9L	Uncertain significance	criteria provided, multiple submitters, no conflicts
1406139	NM_152703.5(SAMD9L):c.944T>G (p.Ile315Arg)	SAMD9L	Uncertain significance	criteria provided, multiple submitters, no conflicts
1407336	NM_152703.5(SAMD9L):c.1364T>C (p.Val455Ala)	SAMD9L	Uncertain significance	criteria provided, multiple submitters, no conflicts
1410128	NM_152703.5(SAMD9L):c.1957T>A (p.Leu653Met)	SAMD9L	Uncertain significance	criteria provided, multiple submitters, no conflicts
1426492	NM_152703.5(SAMD9L):c.3410G>A (p.Gly1137Glu)	SAMD9L	Uncertain significance	criteria provided, multiple submitters, no conflicts
1437441	NM_152703.5(SAMD9L):c.4259G>A (p.Ser1420Asn)	SAMD9L	Uncertain significance	criteria provided, multiple submitters, no conflicts
1679738	NM_152703.5(SAMD9L):c.2052A>C (p.Glu684Asp)	SAMD9L	Uncertain significance	criteria provided, single submitter
1922426	NM_152703.5(SAMD9L):c.853C>T (p.Arg285Trp)	SAMD9L	Uncertain significance	criteria provided, multiple submitters, no conflicts
1959197	NM_152703.5(SAMD9L):c.1096T>C (p.Phe366Leu)	SAMD9L	Uncertain significance	criteria provided, multiple submitters, no conflicts
2136077	NM_152703.5(SAMD9L):c.4540A>G (p.Lys1514Glu)	SAMD9L	Uncertain significance	criteria provided, multiple submitters, no conflicts
2163451	NM_152703.5(SAMD9L):c.994dup (p.Ile332fs)	SAMD9L	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 10 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SCNN1A	Orphanet:130	Brugada syndrome
SCNN1A	Orphanet:171876	Generalized pseudohypoaldosteronism type 1
SCNN1A	Orphanet:526	Liddle syndrome
SCNN1A	Orphanet:60033	Idiopathic bronchiectasis
SCNN1G	Orphanet:171876	Generalized pseudohypoaldosteronism type 1
SCNN1G	Orphanet:526	Liddle syndrome
SCNN1G	Orphanet:60033	Idiopathic bronchiectasis
SAMD9L	Orphanet:2585	Ataxia-pancytopenia syndrome
SAMD9L	Orphanet:619367	SAMD9L-associated autoinflammatory syndrome
SAMD9L	Orphanet:631106	Spinocerebellar ataxia type 49

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SCNN1A	HGNC:10599	ENSG00000111319	P37088	Epithelial sodium channel subunit alpha	clinvar
SCNN1G	HGNC:10602	ENSG00000166828	P51170	Epithelial sodium channel subunit gamma	clinvar
SAMD9L	HGNC:1349	ENSG00000177409	Q8IVG5	Sterile alpha motif domain-containing protein 9-like	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SCNN1A	Epithelial sodium channel subunit alpha	This is one of the three pore-forming subunits of the heterotrimeric epithelial sodium channel (ENaC), a critical regulator of sodium balance and fluid homeostasis.
SCNN1G	Epithelial sodium channel subunit gamma	This is one of the three pore-forming subunits of the heterotrimeric epithelial sodium channel (ENaC), a critical regulator of sodium balance and fluid homeostasis.
SAMD9L	Sterile alpha motif domain-containing protein 9-like	May be involved in endosome fusion.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 3 · 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	3	1.8×	0.174

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SCNN1A	Other/Unknown	no		ENaC, ENaC_chordates, ENaC_CS
SCNN1G	Other/Unknown	no		ENaC, ENaC_chordates, ENaC_CS
SAMD9L	Other/Unknown	no		SAM, SAM/pointed_sf

Expression context

Cohort genes with no expression data: 0.

3 cohort genes 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
metanephros cortex	1
nasal cavity epithelium	1
right uterine tube	1
bronchial epithelial cell	1
kidney epithelium	1
renal medulla	1
buccal mucosa cell	1
leukocyte	1
pancreatic ductal cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SCNN1A	283	broad	marker	nasal cavity epithelium, metanephros cortex, right uterine tube
SCNN1G	133	broad	marker	renal medulla, kidney epithelium, bronchial epithelial cell
SAMD9L	231	ubiquitous	marker	pancreatic ductal cell, buccal mucosa cell, leukocyte

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SAMD9L	1,608
SCNN1A	1,300
SCNN1G	1,037

Intra-cohort edges

A	B	Sources
SCNN1A	SCNN1G	biogrid_interaction, intact, string_interaction

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SCNN1G	P51170	5
SCNN1A	P37088	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SAMD9L	Q8IVG5	83.85

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. Enrichment computed across 3 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Sensory perception of salty taste	2	1903.3×	1e-06	SCNN1A, SCNN1G
Sensory perception of taste	2	335.9×	3e-05	SCNN1A, SCNN1G
Stimuli-sensing channels	2	135.9×	1e-04	SCNN1A, SCNN1G
Ion channel transport	2	96.0×	1e-04	SCNN1A, SCNN1G
Sensory Perception	2	95.2×	1e-04	SCNN1A, SCNN1G
Transport of small molecules	2	25.1×	0.002	SCNN1A, SCNN1G

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
sensory perception of salty taste	2	4213.0×	5e-07	SCNN1A, SCNN1G
cellular response to aldosterone	2	2407.4×	7e-07	SCNN1A, SCNN1G
cellular response to vasopressin	2	2106.5×	7e-07	SCNN1A, SCNN1G
multicellular organismal-level water homeostasis	2	1685.2×	7e-07	SCNN1A, SCNN1G
sensory perception of sour taste	2	1685.2×	7e-07	SCNN1A, SCNN1G
sodium ion homeostasis	2	936.2×	2e-06	SCNN1A, SCNN1G
intracellular sodium ion homeostasis	2	766.0×	2e-06	SCNN1A, SCNN1G
cellular response to acidic pH	2	732.7×	2e-06	SCNN1A, SCNN1G
sodium ion import across plasma membrane	2	624.1×	3e-06	SCNN1A, SCNN1G
regulation of blood pressure	2	221.7×	2e-05	SCNN1A, SCNN1G
sodium ion transmembrane transport	2	203.0×	2e-05	SCNN1A, SCNN1G

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 2

Druggability breadth: 2 of 3 evidence-associated genes (67%) 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
SCNN1A	AMILORIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SCNN1A	2	4
SCNN1G	0	0
SAMD9L	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
AMILORIDE	4	SCNN1A
552-02 FREE BASE	2	SCNN1A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SCNN1A	6	Binding:4, ADMET:1, Functional:1
SCNN1G	5	Binding:3, ADMET:1, Functional:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Drug repurposing candidates

2 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

Compound	Max phase	Cohort target (bioactivity)
AMILORIDE	4	SCNN1A
552-02 FREE BASE	2	SCNN1A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	SCNN1A
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	2	SCNN1G, SAMD9L

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
SCNN1G	5	—
SAMD9L	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.