Monosomy 7 myelodysplasia and leukemia syndrome 2

Summary

Monosomy 7 myelodysplasia and leukemia syndrome 2 (MONDO:0030801) is a cancer caused by SAMD9 (GenCC Strong), with 1 cohort gene.

At a glance

• Classification: Cancer
• Causal gene: SAMD9 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 59

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	monosomy 7 myelodysplasia and leukemia syndrome 2
Mondo ID	MONDO:0030801
OMIM	619041
UMLS	C5436668
MedGen	1762901
GARD	0018506
Is cancer (heuristic)	yes

Also known as: M7MLS2 · monosomy 7 myelodysplasia and leukemia syndrome 2

Data availability: 59 ClinVar variants · 3 GenCC gene-disease records.

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 2

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

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

59 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
985307	NM_017654.4(SAMD9):c.2944C>T (p.Arg982Cys)	SAMD9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
988626	NM_017654.4(SAMD9):c.3406G>C (p.Glu1136Gln)	SAMD9	Pathogenic	no assertion criteria provided
988627	NM_017654.4(SAMD9):c.2026A>G (p.Lys676Glu)	SAMD9	Pathogenic	no assertion criteria provided
1805947	NM_017654.4(SAMD9):c.4532T>C (p.Leu1511Ser)	SAMD9	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1174761	NM_017654.4(SAMD9):c.2686T>C (p.Tyr896His)	SAMD9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1422840	NM_017654.4(SAMD9):c.2254T>A (p.Trp752Arg)	SAMD9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1648073	NM_017654.4(SAMD9):c.4413G>A (p.Met1471Ile)	SAMD9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
225463	NM_017654.4(SAMD9):c.460C>T (p.Gln154Ter)	SAMD9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
709973	NM_017654.4(SAMD9):c.4724G>A (p.Gly1575Glu)	SAMD9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
992633	NM_017654.4(SAMD9):c.3878G>A (p.Arg1293Gln)	SAMD9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1029634	NM_017654.4(SAMD9):c.3728_3731del (p.Asn1243fs)	SAMD9	Uncertain significance	criteria provided, multiple submitters, no conflicts
1336034	NM_017654.4(SAMD9):c.4001G>T (p.Arg1334Ile)	SAMD9	Uncertain significance	criteria provided, multiple submitters, no conflicts
1336910	NM_017654.4(SAMD9):c.374C>T (p.Pro125Leu)	SAMD9	Uncertain significance	criteria provided, multiple submitters, no conflicts
1337200	NM_017654.4(SAMD9):c.2611G>T (p.Glu871Ter)	SAMD9	Uncertain significance	criteria provided, multiple submitters, no conflicts
1337330	NM_017654.4(SAMD9):c.3118C>G (p.Arg1040Gly)	SAMD9	Uncertain significance	criteria provided, multiple submitters, no conflicts
1337472	NM_017654.4(SAMD9):c.3403A>G (p.Ile1135Val)	SAMD9	Uncertain significance	criteria provided, multiple submitters, no conflicts
1347521	NM_017654.4(SAMD9):c.1460A>G (p.His487Arg)	SAMD9	Uncertain significance	criteria provided, multiple submitters, no conflicts
1366621	NM_017654.4(SAMD9):c.13C>A (p.Leu5Ile)	SAMD9	Uncertain significance	criteria provided, multiple submitters, no conflicts
1399401	NM_017654.4(SAMD9):c.3260C>T (p.Ala1087Val)	SAMD9	Uncertain significance	criteria provided, multiple submitters, no conflicts
1477668	NM_017654.4(SAMD9):c.2202T>A (p.His734Gln)	SAMD9	Uncertain significance	criteria provided, multiple submitters, no conflicts
1497031	NM_017654.4(SAMD9):c.83T>C (p.Ile28Thr)	SAMD9	Uncertain significance	criteria provided, multiple submitters, no conflicts
1506133	NM_017654.4(SAMD9):c.29del (p.Asn10fs)	SAMD9	Uncertain significance	criteria provided, multiple submitters, no conflicts
1510921	NM_017654.4(SAMD9):c.3721G>C (p.Asp1241His)	SAMD9	Uncertain significance	criteria provided, multiple submitters, no conflicts
1517435	NM_017654.4(SAMD9):c.4630G>A (p.Gly1544Arg)	SAMD9	Uncertain significance	criteria provided, multiple submitters, no conflicts
1519768	NM_017654.4(SAMD9):c.2380G>A (p.Val794Ile)	SAMD9	Uncertain significance	criteria provided, multiple submitters, no conflicts
1521693	NM_017654.4(SAMD9):c.2581_2582insT (p.Glu861fs)	SAMD9	Uncertain significance	criteria provided, multiple submitters, no conflicts
1691671	NM_017654.4(SAMD9):c.3227A>G (p.His1076Arg)	SAMD9	Uncertain significance	criteria provided, multiple submitters, no conflicts
1699235	NM_017654.4(SAMD9):c.1504A>C (p.Ser502Arg)	SAMD9	Uncertain significance	criteria provided, single submitter
1805924	NM_017654.4(SAMD9):c.3136G>A (p.Glu1046Lys)	SAMD9	Uncertain significance	criteria provided, single submitter
1878952	NM_017654.4(SAMD9):c.4496A>G (p.Asp1499Gly)	SAMD9	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 14 · Orphanet: 2 · 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
SAMD9	Strong	Autosomal dominant	monosomy 7 myelodysplasia and leukemia syndrome 2	14

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SAMD9	Orphanet:306658	Familial normophosphatemic tumoral calcinosis
SAMD9	Orphanet:494433	MIRAGE 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
SAMD9	HGNC:1348	ENSG00000205413	Q5K651	Sterile alpha motif domain-containing protein 9	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SAMD9	Sterile alpha motif domain-containing protein 9	Double-stranded nucleic acid binding that acts as an antiviral factor by playing an essential role in the formation of cytoplasmic antiviral granules.

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)
SAMD9	Other/Unknown	no		SAM, SAM/pointed_sf, P-loop_NTPase

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
amniotic fluid	1
epithelium of esophagus	1
esophagus squamous epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SAMD9	247	ubiquitous	marker	esophagus squamous epithelium, amniotic fluid, epithelium of esophagus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SAMD9	1,316

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SAMD9	Q5K651	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
endosomal vesicle fusion	1	1123.5×	0.002	SAMD9
innate immune response	1	33.6×	0.030	SAMD9

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
SAMD9	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).

Drug repurposing candidates

0 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.

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	SAMD9

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)
SAMD9	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.