Inherited acute myeloid leukemia
disease diseaseOn this page
Also known as familial AMLhereditary acute myeloid leukaemiahereditary acute myeloid leukemiainherited AMLPure familial acute myeloid leukaemiaPure familial acute myeloid leukemiaPure familial AML
Summary
Inherited acute myeloid leukemia (MONDO:0017893) is a cancer with 2 cohort genes (2 CIViC-evidence somatic drivers; 2 ClinVar predisposition records).
At a glance
- Classification: Cancer
- Cohort genes: 2
- ClinVar variants: 2
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | inherited acute myeloid leukemia |
| Mondo ID | MONDO:0017893 |
| Orphanet | 319465 |
| NCIT | C7175 |
| SNOMED CT | 764940002 |
| UMLS | C4707228 |
| MedGen | 1634915 |
| GARD | 0017450 |
| Is cancer (heuristic) | yes |
Also known as: familial AML · hereditary acute myeloid leukaemia · hereditary acute myeloid leukemia · inherited AML · Pure familial acute myeloid leukaemia · Pure familial acute myeloid leukemia · Pure familial AML
Data availability: 2 ClinVar variants.
Disease family
An umbrella term covering 3 Mondo subtypes.
Classification path: human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › hematopoietic and lymphoid system neoplasm › hematopoietic and lymphoid cell neoplasm › leukemia › myeloid leukemia › acute myeloid leukemia › inherited acute myeloid leukemia
Related subtypes (77): childhood acute myeloid leukemia, acute monocytic leukemia, acute myeloid leukemia with t(8;21)(q22;q22) translocation, acute myeloid leukemia by FAB classification, acute myeloid leukemia with CEBPA somatic mutations, acute myeloid leukemia with t(8;16)(p11;p13) translocation, acute myeloid leukemia with t(6;9)(p23;q34), acute myeloid leukemia with t(9;11)(p22;q23), acute myeloid leukemia with inv3(p21;q26.2) or t(3;3)(p21;q26.2), megakaryoblastic acute myeloid leukemia with t(1;22)(p13;q13), acute myeloid leukemia with NPM1 somatic mutations, acute myeloid leukemia with multilineage dysplasia, therapy related acute myeloid leukemia and myelodysplastic syndrome, acute leukemia of ambiguous lineage, acute myeloid leukemia with abnormal bone marrow eosinophils inv(16)(p13q22) or t(16;16)(p13;q22), acute myeloid leukemia with 11q23 abnormalities, acute myeloid leukemia with BCR-ABL1, acute myeloid leukemia with mutated NPM1, acute myeloid leukemia, inv(16)(p13.1;q22), acute myeloid leukemia, t(16;16)(p13.1;q22), acute myeloid leukemia, t(15;17)(q24;q21), acute myeloid leukemia, t(9;11)(p21.3;q23.3), acute myeloid leukemia, t(10;11)(p12;q23), acute myeloid leukemia, t(10;11)(p11.2;q23), acute myeloid leukemia, t(1;11)(q21;q23), acute myeloid leukemia, t(4;11)(q21;q23), acute myeloid leukemia, t(6;11)(q27;q23), acute myeloid leukemia, t(6;9)(p23;q34.1), acute myeloid leukemia, t(11;19)(q23;p13), acute myeloid leukemia, t(11;19)(q23;p13.1), acute myeloid leukemia, t(11;19)(q23.3;p13.3), acute myeloid leukemia, t(v;11q23.3), acute myeloid leukemia, Monosomy 7, acute myeloid leukemia, Monosomy 5, acute myeloid leukemia, Trisomy 8, acute myeloid leukemia, der12p, acute myeloid leukemia, t(2;12), acute myeloid leukemia, t(11;17), acute myeloid leukemia, t(8;16), acute myeloid leukemia, t(1;22), acute myeloid leukemia, t(5;11)(q35;p15), acute myeloid leukemia, t(7;12)(q36;p13), acute myeloid leukemia, t(9;22)(q34.1;q11.2), acute myeloid leukemia, inv(3)(q21.3;q26.2), acute myeloid leukemia, t(3;3)(q21.3;q26.2), acute myeloid leukemia, t(3;12)(q23;p12.3), acute myeloid leukemia, del(5q31-q32), acute myeloid leukemia, del(13q14-q21), acute myeloid leukemia, loss of chromosome 17p, acute myeloid leukemia, MLL gene rearrangement, acute myeloid leukemia, Non-KMT2A MLLT10 rearrangement positive, acute myeloid leukemia, inv(16)(p13.3;q24.3), acute myeloid leukemia, t(11;15)(p15;q35), acute myeloid leukemia, t(16;21)(q24;q22), acute myeloid leukemia, t(3;5)(q25;q34), acute myeloid leukemia, t(16;21)(p11;q22), acute myeloid leukemia, monoallelic CEBPA gene mutation, acute myeloid leukemia, biallelic CEBPA gene mutation, acute myeloid leukemia, CEBPA gene mutation, acute myeloid leukemia, FLT3 internal tandem duplication, acute myeloid leukemia, FLT3 tyrosine kinase domain point mutation, acute myeloid leukemia, WT1 gene mutation, acute myeloid leukemia, KIT exon 17 mutation, acute myeloid leukemia, KIT exon 8 mutation, acute myeloid leukemia, KIT gene mutation, acute myeloid leukemia, GATA1 gene mutation, acute myeloid leukemia, RUNX1 gene mutation, acute myeloid leukemia, PTPN11 gene mutation, acute myeloid leukemia, NRAS gene mutation, acute myeloid leukemia, KRAS gene mutation, core binding factor acute myeloid leukemia, acute myeloid leukemia, t(8;21)(q22; q22.1), acute myeloid leukemia, t(1;22)(p13;q13), acute myeloid leukemia with CBFA2T3-GLIS2 fusion, acute myeloid leukemia with FUS-ERG fusion, acute myeloid leukemia with MNX1-ETV6 fusion, acute myeloid leukemia with NPM1-MLF1 fusion
Subtypes (3): acute promyelocytic leukemia, mixed phenotype acute leukemia with t(9;22)(q34.1;q11.2), mixed phenotype acute leukemia with t(v;11q23.3)
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
2 retrieved; paginated sample, class counts are floors:
1 pathogenic, 1 likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1327658 | NM_016222.4(DDX41):c.931C>T (p.Arg311Ter) | DDX41 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 2626812 | NM_017612.5(ZCCHC8):c.551G>A (p.Gly184Glu) | ZCCHC8 | Likely pathogenic | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
Somatic driver evidence (intOGen + CIViC, cohort fanout)
| Gene | intOGen role | Cancer types | CIViC |
|---|---|---|---|
| DDX41 | CIViC #11932 | ||
| ZCCHC8 | Act | STAD |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| DDX41 | Orphanet:488647 | DDX41-related hematologic malignancy predisposition syndrome |
Cohort genes → proteins
2 cohort genes, 2 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 2 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| DDX41 | HGNC:18674 | ENSG00000183258 | Q9UJV9 | Probable ATP-dependent RNA helicase DDX41 | clinvar |
| ZCCHC8 | HGNC:25265 | ENSG00000033030 | Q6NZY4 | Zinc finger CCHC domain-containing protein 8 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| DDX41 | Probable ATP-dependent RNA helicase DDX41 | Multifunctional protein that participates in many aspects of cellular RNA metabolism. |
| ZCCHC8 | Zinc finger CCHC domain-containing protein 8 | Scaffolding subunit of the trimeric nuclear exosome targeting (NEXT) complex that is involved in the surveillance and turnover of aberrant transcripts and non-coding RNAs. |
Protein-family classification
Druggable: 0 · Difficult: 1 · 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 |
|---|---|---|---|
| Transcription factor | 1 | 4.1× | 0.455 |
| Other/Unknown | 1 | 0.9× | 0.805 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| DDX41 | Other/Unknown | no | Helicase_C-like, DEAD/DEAH_box_helicase_dom, Helicase_ATP-bd | |
| ZCCHC8 | Transcription factor | no | Znf_CCHC, PSP_pro-rich, NEXT_complex_subunit_ZCCHC8 |
Expression context
Cohort genes with no expression data: 0.
2 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) | 2 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| granulocyte | 1 |
| lower esophagus mucosa | 1 |
| right frontal lobe | 1 |
| cervix squamous epithelium | 1 |
| endothelial cell | 1 |
| sperm | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| DDX41 | 274 | ubiquitous | marker | granulocyte, right frontal lobe, lower esophagus mucosa |
| ZCCHC8 | 282 | ubiquitous | marker | cervix squamous epithelium, sperm, endothelial cell |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| DDX41 | 2,388 |
| ZCCHC8 | 1,903 |
Structural data
PDB: 2 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| ZCCHC8 | Q6NZY4 | 8 |
| DDX41 | Q9UJV9 | 5 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 6. Enrichment computed across 2 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 |
|---|---|---|---|---|
| STING mediated induction of host immune responses | 1 | 519.1× | 0.005 | DDX41 |
| IRF3-mediated induction of type I IFN | 1 | 407.9× | 0.005 | DDX41 |
| Regulation of innate immune responses to cytosolic DNA | 1 | 380.7× | 0.005 | DDX41 |
| Nuclear RNA decay | 1 | 154.3× | 0.010 | ZCCHC8 |
| Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex | 1 | 81.6× | 0.015 | ZCCHC8 |
| mRNA Splicing - Major Pathway | 1 | 27.3× | 0.036 | DDX41 |
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 |
|---|---|---|---|---|
| co-transcriptional lncRNA 3’ end processing, cleavage and polyadenylation pathway | 1 | 8426.0× | 7e-04 | ZCCHC8 |
| mRNA splicing, via spliceosome | 2 | 91.6× | 7e-04 | DDX41, ZCCHC8 |
| snRNA catabolic process | 1 | 2808.7× | 0.001 | ZCCHC8 |
| cGAS/STING signaling pathway | 1 | 1685.2× | 0.002 | DDX41 |
| mRNA 3’-end processing | 1 | 280.9× | 0.008 | ZCCHC8 |
| cellular response to interferon-beta | 1 | 263.3× | 0.008 | DDX41 |
| RNA processing | 1 | 109.4× | 0.016 | ZCCHC8 |
| cell population proliferation | 1 | 51.4× | 0.029 | DDX41 |
| defense response to virus | 1 | 34.7× | 0.038 | DDX41 |
| cell differentiation | 1 | 14.6× | 0.075 | DDX41 |
| apoptotic process | 1 | 14.3× | 0.075 | DDX41 |
| positive regulation of transcription by RNA polymerase II | 1 | 7.4× | 0.130 | DDX41 |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 1 · Undrugged: 1
Druggability breadth: 2 of 2 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 |
|---|---|---|
| DDX41 | 1 | 2 |
| ZCCHC8 | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| MOLIBRESIB | 2 | DDX41 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| DDX41 | 7 | Binding:7 |
| ZCCHC8 | 1 | Binding:1 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Drug repurposing candidates
1 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) |
|---|---|---|
| MOLIBRESIB | 2 | DDX41 |
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 | 1 | DDX41 |
| C | Druggable family + PDB, no drug | 0 | |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 1 | ZCCHC8 |
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) |
|---|---|---|
| ZCCHC8 | 1 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.