anemia, congenital dyserythropoietic, type IVb

Summary

anemia, congenital dyserythropoietic, type IVb (MONDO:0975829) is a disease caused by KLF1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: KLF1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 9

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	anemia, congenital dyserythropoietic, type IVb
Mondo ID	MONDO:0975829
OMIM	620969
DOID	DOID:0051002
UMLS	C5975438
MedGen	1874968
GARD	0027326
Is cancer (heuristic)	no

Data availability: 9 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › hematologic disorder › anemia › normocytic anemia › hemolytic anemia › familial hemolytic anemia › congenital dyserythropoietic anemia › anemia, congenital dyserythropoietic, type IVb

Related subtypes (8): congenital dyserythropoietic anemia type 3, congenital dyserythropoietic anemia type 2, X-linked dyserythropoetic anemia with abnormal platelets and neutropenia, pancreatic insufficiency-anemia-hyperostosis syndrome, congenital dyserythropoietic anemia type 4, thrombocytopenia with congenital dyserythropoietic anemia, congenital dyserythropoietic anemia type 1, Anemia, congenital dyserythropoietic, type IIIb, autosomal recessive

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

9 retrieved; paginated sample, class counts are floors:

4 pathogenic, 2 pathogenic/likely pathogenic, 2 pathogenic; affects, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
3252231	NM_006563.5(KLF1):c.900_903dup (p.Thr302fs)	KLF1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3358908	KLF1, -154C-T	KLF1	Pathogenic	no assertion criteria provided
3358909	NM_006563.5(KLF1):c.902G>A (p.Arg301His)	KLF1	Pathogenic; Affects	no assertion criteria provided
3358910	NM_006563.5(KLF1):c.172C>T (p.Gln58Ter)	KLF1	Pathogenic	no assertion criteria provided
3358911	KLF1, TRP30TER	KLF1	Pathogenic; Affects	no assertion criteria provided
3358912	NM_006563.5(KLF1):c.1012C>A (p.Pro338Thr)	KLF1	Pathogenic	no assertion criteria provided
56891	NM_006563.5(KLF1):c.892G>C (p.Ala298Pro)	KLF1	Pathogenic	criteria provided, multiple submitters, no conflicts
8999	NM_006563.5(KLF1):c.954dup (p.Arg319fs)	KLF1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
100799	NM_006563.5(KLF1):c.519_525dup (p.Gly176fs)	KLF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 3 · 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
KLF1	Definitive	Autosomal dominant	congenital dyserythropoietic anemia type 4	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KLF1	Orphanet:251380	Hereditary persistence of fetal hemoglobin-sickle cell disease syndrome
KLF1	Orphanet:293825	Congenital dyserythropoietic anemia type IV
KLF1	Orphanet:46532	Hereditary persistence of fetal hemoglobin-beta-thalassemia 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
KLF1	HGNC:6345	ENSG00000105610	Q13351	Krueppel-like factor 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KLF1	Krueppel-like factor 1	Transcription regulator of erythrocyte development that probably serves as a general switch factor during erythropoiesis.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KLF1	Transcription factor	no		Znf_C2H2_type, EKLF_TAD2, EKLF_TAD1

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
blood	1
bone marrow	1
trabecular bone tissue	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KLF1	86	tissue_specific	marker	trabecular bone tissue, bone marrow, blood

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KLF1	1,682

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KLF1	Q13351	3

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
cellular response to endothelin	1	1404.3×	0.004	KLF1
maternal process involved in female pregnancy	1	936.2×	0.004	KLF1
protein destabilization	1	290.6×	0.007	KLF1
erythrocyte differentiation	1	267.5×	0.007	KLF1
ubiquitin-dependent protein catabolic process	1	74.2×	0.022	KLF1
regulation of DNA-templated transcription	1	31.6×	0.041	KLF1
positive regulation of DNA-templated transcription	1	27.9×	0.041	KLF1
regulation of transcription by RNA polymerase II	1	11.7×	0.086	KLF1

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
KLF1	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
KLF1	4	Binding:4

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	KLF1

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)
KLF1	4	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.