KLF1

Chr 19ADAR

KLF transcription factor 1

Also known as: CDAN4A, CDAN4B, EKLF, EKLF/KLF1

NCBI Gene: 10661ENSG00000105610UniProt: Q13351

This gene encodes a hematopoietic-specific transcription factor that induces high-level expression of adult beta-globin and other erythroid genes. The zinc-finger protein binds to the DNA sequence CCACACCCT found in the beta hemoglobin promoter. Heterozygous loss-of-function mutations in this gene result in the dominant In(Lu) blood phenotype. [provided by RefSeq, Oct 2009]

Primary Disease Associations & Inheritance

[Hereditary persistence of fetal hemoglobin]MIM #613566
AD
Anemia, congenital dyserythropoietic, type IVbMIM #620969
AR
Anemia, dyserythropoietic congenital, type IVaMIM #613673
AD
Blood group--Lutheran inhibitorMIM #111150
AD
272
ClinVar variants
46
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— KLF1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
46 Pathogenic / Likely Pathogenic· 137 VUS of 272 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.13LOEUF
pLI 0.000
Z-score 1.26
OE 0.60 (0.34–1.13)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.85Z-score
OE missense 0.83 (0.73–0.94)
171 obs / 205.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.60 (0.34–1.13)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.83 (0.73–0.94)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.92
0≤1.21.6
LoF obs/exp: 7 / 11.7Missense obs/exp: 171 / 205.3Syn Z: 0.61

ClinVar Variant Classifications

272 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35
Likely Pathogenic11
VUS137
Likely Benign61
Benign10
Conflicting14
35
Pathogenic
11
Likely Pathogenic
137
VUS
61
Likely Benign
10
Benign
14
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
6
26
0
35
Likely Pathogenic
4
3
4
0
11
VUS
1
115
19
2
137
Likely Benign
0
8
11
42
61
Benign
0
1
9
0
10
Conflicting
—14
Total81336944268

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

KLF1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

KLF1-related anemia, dyserythropoietic congenital

definitive
ADDominant NegativeAltered Gene Product Structure
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

[Hereditary persistence of fetal hemoglobin]

MIM #613566

Molecular basis of disorder known

Autosomal dominant

Anemia, congenital dyserythropoietic, type IVb

MIM #620969

Molecular basis of disorder known

Autosomal recessive

Anemia, dyserythropoietic congenital, type IVa

MIM #613673

Molecular basis of disorder known

Autosomal dominant

Blood group--Lutheran inhibitor

MIM #111150

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Lutheran.
Daniels G·Immunohematology
2009Review
Base-editing-mediated dissection of a γ-globin cis-regulatory element for the therapeutic reactivation of fetal hemoglobin expression.
Antoniou P et al.·Nat Commun
2022
Severe anemia caused by dominant mutations in Krüppel-like factor 1 (KLF1).
Kulczynska-Figurny K et al.·Mutat Res Rev Mutat Res
2020Review
Genetic control of erythropoiesis.
Tumburu L et al.·Curr Opin Hematol
2017Review
Congenital dyserythropoietic anemias.
Iolascon A et al.·Curr Opin Hematol
2011Review
Impact of transcription factors KLF1 and GATA1 on red blood cell antigen expression: a review.
Lopez GH et al.·Immunohematology
2024Review
CLPTM1L interacts with ERLIN2 to stabilize SREBP1 and drive tumorigenesis in nasopharyngeal carcinoma.
Zhang J et al.·Cell Death Dis
2025
Genetic Variants Within the Erythroid Transcription Factor, KLF1, and Reduction of the Expression of Lutheran and Other Blood Group Antigens: Review of the In(Lu) Phenotype.
Fraser NS et al.·Transfus Med Rev
2019Review
Krüppel-like factor 1: hematologic phenotypes associated with KLF1 gene mutations.
Waye JS et al.·Int J Lab Hematol
2015Review
Orchestration of late events in erythropoiesis by KLF1/EKLF.
Gnanapragasam MN et al.·Curr Opin Hematol
2017Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Orai1 acts as a novel Ca2+ signal switch, balancing erythropoiesis through KLF1 regulation.
Lee YY et al.·Exp Mol Med
2026
KLF1 Exerts Pro-Tumour Role in Liver Cancer via Inhibiting ACSL4/LPCAT3-Regulated Ferroptosis.
Chen Z et al.·J Cell Mol Med
2026🔓 Open Access
Nap1L4a Cooperates with Scl/Klf1 to Recruit H2A.Z in Mediating Interactions Among Cis-Regulatory Elements and Transcription Required for Primitive Erythropoiesis in Zebrafish.
Shi J et al.·Adv Sci (Weinh)
2026🔓 Open AccessFunctional
KLF1 coordinates specialized transcriptional networks required to maintain the integrity of terminal erythropoiesis.
Gnanapragasam MN et al.·J Cell Sci
2025🔓 Open Access
Association Between KLF1, BCL11A and HBS1L-MYB Polymorphisms and Phenotypes With β-Thalassemia Patients in Hainan.
Hu J et al.·Mol Genet Genomic Med
2025🔓 Open AccessCohort
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
EKLF Mutations in Beta Thalassemia Patients

Detection of Krupple Like Factor -1(KLF1/ EKLF) DNA Mutations in Beta Thalassemia Patients

NOT YET RECRUITING
NCT06433570Assiut UniversityStarted 2024-06
multiplex PCR

External Resources

Links to major genomics databases and tools