Autosomal dominant aplasia and myelodysplasia

Summary

Autosomal dominant aplasia and myelodysplasia (MONDO:0013851) is a disease caused by SRP72 (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: SRP72 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 93

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		6	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal dominant aplasia and myelodysplasia
Mondo ID	MONDO:0013851
OMIM	614675
Orphanet	314399
UMLS	C3808553
MedGen	814883
GARD	0017420
Is cancer (heuristic)	no

Also known as: autosomal dominant aplastic anaemia and myelodysplasia · autosomal dominant aplastic anemia and myelodysplasia · BMFS1 · bone marrow failure syndrome 1 · bone marrow failure syndrome type 1

Data availability: 93 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › immune system disorder › bone marrow disorder › bone marrow failure syndrome › autosomal dominant aplasia and myelodysplasia

Related subtypes (7): pancytopenia-developmental delay syndrome, bone marrow failure syndrome 3, bone marrow failure syndrome 4, bone marrow failure syndrome 6, AMED syndrome, digenic, bone marrow failure syndrome 5, Ziegler-Huang syndrome

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

93 retrieved; paginated sample, class counts are floors:

51 uncertain significance, 20 benign, 12 benign/likely benign, 8 conflicting classifications of pathogenicity, 2 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
349113	NM_006947.4(SRP72):c.20G>A (p.Gly7Glu)	LOC129992625	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
349115	NM_006947.4(SRP72):c.23G>A (p.Gly8Glu)	SRP72	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
349116	NM_006947.4(SRP72):c.37G>T (p.Ala13Ser)	SRP72	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
349118	NM_006947.4(SRP72):c.133G>A (p.Val45Ile)	SRP72	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
349121	NM_006947.4(SRP72):c.406G>A (p.Val136Ile)	SRP72	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
349124	NM_006947.4(SRP72):c.973A>G (p.Lys325Glu)	SRP72	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
349126	NM_006947.4(SRP72):c.1225-6G>A	SRP72	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
904986	NM_006947.4(SRP72):c.110-5T>G	SRP72	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1803128	NM_006947.4(SRP72):c.-10C>T	LOC129992625	Uncertain significance	criteria provided, single submitter
3590628	NM_006947.4(SRP72):c.26T>C (p.Val9Ala)	LOC129992625	Uncertain significance	criteria provided, single submitter
3962024	NM_006947.4(SRP72):c.5C>T (p.Ala2Val)	LOC129992625	Uncertain significance	criteria provided, single submitter
1336342	NM_006947.4(SRP72):c.622C>T (p.Arg208Cys)	SRP72	Uncertain significance	criteria provided, multiple submitters, no conflicts
1443238	NM_006947.4(SRP72):c.623G>A (p.Arg208His)	SRP72	Uncertain significance	criteria provided, multiple submitters, no conflicts
1723735	NM_006947.4(SRP72):c.25dup (p.Val9fs)	SRP72	Uncertain significance	criteria provided, multiple submitters, no conflicts
2585164	NM_006947.4(SRP72):c.1900G>C (p.Val634Leu)	SRP72	Uncertain significance	criteria provided, multiple submitters, no conflicts
2654771	NM_006947.4(SRP72):c.122A>G (p.Asn41Ser)	SRP72	Uncertain significance	criteria provided, multiple submitters, no conflicts
2776917	NM_006947.4(SRP72):c.1282G>T (p.Val428Phe)	SRP72	Uncertain significance	criteria provided, multiple submitters, no conflicts
2873594	NM_006947.4(SRP72):c.770C>G (p.Pro257Arg)	SRP72	Uncertain significance	criteria provided, multiple submitters, no conflicts
31659	NM_006947.4(SRP72):c.1064_1065del (p.Thr355fs)	SRP72	Uncertain significance	criteria provided, single submitter
31660	NM_006947.4(SRP72):c.620G>A (p.Arg207His)	SRP72	Uncertain significance	criteria provided, multiple submitters, no conflicts
3240544	NM_006947.4(SRP72):c.50A>G (p.Glu17Gly)	SRP72	Uncertain significance	criteria provided, multiple submitters, no conflicts
3341439	NM_006947.4(SRP72):c.308G>A (p.Ser103Asn)	SRP72	Uncertain significance	criteria provided, multiple submitters, no conflicts
3377807	NM_006947.4(SRP72):c.1843G>T (p.Ala615Ser)	SRP72	Uncertain significance	criteria provided, single submitter
3391157	NM_006947.4(SRP72):c.253G>T (p.Ala85Ser)	SRP72	Uncertain significance	criteria provided, single submitter
349140	NM_006947.4(SRP72):c.*194G>A	SRP72	Uncertain significance	criteria provided, single submitter
349141	NM_006947.4(SRP72):c.*221A>G	SRP72	Uncertain significance	criteria provided, single submitter
349142	NM_006947.4(SRP72):c.*227G>A	SRP72	Uncertain significance	criteria provided, single submitter
349143	NM_006947.4(SRP72):c.*321A>G	SRP72	Uncertain significance	criteria provided, single submitter
349145	NM_006947.4(SRP72):c.*407T>C	SRP72	Uncertain significance	criteria provided, single submitter
349149	NM_006947.4(SRP72):c.*606A>T	SRP72	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
SRP72	Strong	Autosomal dominant	autosomal dominant aplasia and myelodysplasia	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SRP72	Orphanet:314399	Autosomal dominant aplasia and myelodysplasia

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
SRP72	HGNC:11303	ENSG00000174780	O76094	Signal recognition particle subunit SRP72	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SRP72	Signal recognition particle subunit SRP72	Component of the signal recognition particle (SRP) complex, a ribonucleoprotein complex that mediates the cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER).

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)
SRP72	Other/Unknown	no		TPR-like_helical_dom_sf, Signal_recog_part_SRP72_RNA-bd, TPR_rpt

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
pylorus	1
tendon of biceps brachii	1
visceral pleura	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SRP72	295	ubiquitous	marker	pylorus, tendon of biceps brachii, visceral pleura

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SRP72	2,502

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SRP72	O76094	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
SRP-dependent cotranslational protein targeting to membrane	1	100.2×	0.024	SRP72
Translation	1	62.1×	0.024	SRP72
Metabolism of proteins	1	12.4×	0.081	SRP72

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
SRP-dependent cotranslational protein targeting to membrane	1	2106.5×	5e-04	SRP72

Therapeutics

Drug target analysis

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

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
SRP72	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	SRP72

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SRP72	7	Binding:7

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

1 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.

Compound	Max phase	Cohort target (bioactivity)
MOLIBRESIB	2	SRP72

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	SRP72
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.