KLF1 (KLF transcription factor 1)

Gene

• Entrez ID: 10661
• Gene name: KLF transcription factor 1
• Gene symbol: KLF1
• Synonyms (NCBI Gene): CDAN4A, CDAN4B, EKLF, EKLF/KLF1
• Chromosome: 19
• Chromosome location: 19p13.13
• Summary: 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. Heterozyg

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs137852687	T>A,C	Pathogenic	Coding sequence variant, missense variant, stop gained
rs137852688	G>A,C	Pathogenic, likely-pathogenic	Coding sequence variant, missense variant
rs267607201	C>T	Pathogenic	Missense variant, coding sequence variant
rs267607202	T>A	Pathogenic	Coding sequence variant, stop gained
rs387907598	C>A,G	Pathogenic	Coding sequence variant, missense variant
rs387907599	G>A,T	Pathogenic	Coding sequence variant, missense variant
rs397514445	->C	Pathogenic	Coding sequence variant, frameshift variant
rs397514634	A>C,G	Pathogenic	Coding sequence variant, missense variant
rs398122931	G>A,T	Pathogenic	Coding sequence variant, missense variant, synonymous variant
rs483352838	->GCCGGGC	Benign, likely-pathogenic	Coding sequence variant, frameshift variant
rs483352839	C>T	Likely-pathogenic	Coding sequence variant, missense variant
rs483352840	C>G,T	Likely-pathogenic	Splice donor variant
rs483352841	G>A,C	Likely-pathogenic	Coding sequence variant, missense variant
rs769526751	C>A,G,T	Affects	Missense variant, coding sequence variant, stop gained
rs1297604452	G>A,C,T	Pathogenic	Stop gained, coding sequence variant, synonymous variant
rs1426116895	G>A,T	Affects	Synonymous variant, coding sequence variant, stop gained
rs1568420836	G>-	Pathogenic	Frameshift variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT022111	hsa-miR-125b-5p	Other	20194440
MIRT1096058	hsa-miR-198	CLIP-seq
MIRT1096059	hsa-miR-3192	CLIP-seq
MIRT1096060	hsa-miR-370	CLIP-seq
MIRT1096061	hsa-miR-3918	CLIP-seq
MIRT1096062	hsa-miR-4300	CLIP-seq
MIRT1096063	hsa-miR-4314	CLIP-seq
MIRT1096064	hsa-miR-4529-5p	CLIP-seq
MIRT1096065	hsa-miR-4646-5p	CLIP-seq
MIRT1096066	hsa-miR-4685-5p	CLIP-seq
MIRT1096067	hsa-miR-626	CLIP-seq
MIRT1096068	hsa-miR-920	CLIP-seq
MIRT2025801	hsa-miR-1182	CLIP-seq
MIRT2025802	hsa-miR-1292	CLIP-seq
MIRT2025803	hsa-miR-3122	CLIP-seq
MIRT1096059	hsa-miR-3192	CLIP-seq
MIRT2025804	hsa-miR-326	CLIP-seq
MIRT2025805	hsa-miR-330-5p	CLIP-seq
MIRT2025806	hsa-miR-3913-5p	CLIP-seq
MIRT1096063	hsa-miR-4314	CLIP-seq
MIRT2025807	hsa-miR-4471	CLIP-seq
MIRT1096065	hsa-miR-4646-5p	CLIP-seq
MIRT2025808	hsa-miR-4747-5p	CLIP-seq
MIRT2025809	hsa-miR-593	CLIP-seq
MIRT2025810	hsa-miR-665	CLIP-seq
MIRT2025811	hsa-miR-671-5p	CLIP-seq
MIRT2025812	hsa-miR-9	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
GATA1	Unknown	18487511;20564185
MYB	Activation	20686118

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000785	Component	Chromatin	IDA	21539536
GO:0000785	Component	Chromatin	IEA
GO:0000785	Component	Chromatin	ISA
GO:0000976	Function	Transcription cis-regulatory region binding	IDA	20676099
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA	21539536
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IBA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0003677	Function	DNA binding	IEA
GO:0003700	Function	DNA-binding transcription factor activity	TAS	8924208, 9778250
GO:0005515	Function	Protein binding	IPI	21670263, 32296183
GO:0005634	Component	Nucleus	IDA	21055716, 25585695
GO:0005634	Component	Nucleus	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0006355	Process	Regulation of DNA-templated transcription	IMP	25585695
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA
GO:0006511	Process	Ubiquitin-dependent protein catabolic process	IEP	24139988
GO:0008270	Function	Zinc ion binding	IEA
GO:0030218	Process	Erythrocyte differentiation	IMP	21055716
GO:0031648	Process	Protein destabilization	IEP	24139988
GO:0043130	Function	Ubiquitin binding	EXP	24139988
GO:0043130	Function	Ubiquitin binding	IMP	24139988
GO:0045893	Process	Positive regulation of DNA-templated transcription	IDA	15084587, 20676099, 21055716
GO:0045893	Process	Positive regulation of DNA-templated transcription	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0060135	Process	Maternal process involved in female pregnancy	IEA
GO:1990859	Process	Cellular response to endothelin	IEA

Other IDs

• MIM: 600599
• HGNC: 6345
• e!Ensembl: ENSG00000105610

Protein

• UniProt ID: Q13351
• Protein name: Krueppel-like factor 1 (Erythroid krueppel-like transcription factor) (EKLF)
• Protein function: Transcription regulator of erythrocyte development that probably serves as a general switch factor during erythropoiesis. Is a dual regulator of fetal-to-adult globin switching. Binds to the CACCC box in the beta-globin gene promoter and acts as
• PDB: 2L2I, 2MBH, 2N23
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF16832	EKLF_TAD1	22 → 48	Erythroid krueppel-like transcription factor, transactivation 1	Domain
  PF16833	EKLF_TAD2	59 → 85	Erythroid krueppel-like transcription factor, transactivation 2	Domain
  PF00096	zf-C2H2	279 → 303	Zinc finger, C2H2 type	Domain
  PF00096	zf-C2H2	309 → 333	Zinc finger, C2H2 type	Domain
  PF00096	zf-C2H2	339 → 361	Zinc finger, C2H2 type	Domain

• Tissue specificity: TISSUE SPECIFICITY: Expression restricted to adult bone marrow and fetal liver. Not expressed in myeloid nor lymphoid cell lines. {ECO:0000269|PubMed:8924208, ECO:0000269|PubMed:9119377}.
• Sequence:

  MATAETALPSISTLTALGPFPDTQDDFLKWWRSEEAQDMGPGPPDPTEPPLHVKSEDQPG
  EEEDDERGADATWDLDLLLTNFSGPEPGGAPQTCALAPSEASGAQYPPPPETLGAYAGGP
  GLVAGLLGSEDHSGWVRPALRARAPDAFVGPALAPAPAPEPKALALQPVYPGPGAGSSGG
  YFPRTGLSVPAASGAPYGLLSGYPAMYPAPQYQGHFQLFRGLQGPAPGPATSPSFLSCLG
  PGTVGTGLGGTAEDPGVIAETAPSKRGRRSWARKRQAAHTCAHPGCGKSYTKSSHLKAHL
  RTHTGEKPYACTWEGCGWRFARSDELTRHYRKHTGQRPFRCQLCPRAFSRSDHLALHMKR
  HL

• Sequence length: 362

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Anemia, congenital dyserythropoietic, type IVb	Pathogenic	rs397514445, rs387907598	RCV004758592 RCV004777567	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
BLOOD GROUP--LUTHERAN INHIBITOR	Pathogenic	rs397514445, rs1568420836, rs137852687, rs137852688, rs267607201, rs398122931, rs1297604452, rs387907598, rs387907599	RCV000009562 RCV000009563 RCV000009564 RCV000009565 RCV000990153 RCV000033156 RCV000033157 RCV000050236 RCV000050237	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Congenital dyserythropoietic anemia type 4	Likely pathogenic; Pathogenic	rs483352840, rs267607201, rs387907598, rs387907599	RCV003448264 RCV000009567 RCV000050236 RCV000050237	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
FETAL HEMOGLOBIN QUANTITATIVE TRAIT LOCUS 6	Pathogenic	rs397514445, rs387907598, rs387907599	RCV004732459 RCV000050236 RCV000050237	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
KLF1-related disorder	Pathogenic	rs397514445, rs267607201	RCV004742223 RCV005887578	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ANEMIA, CONGENITAL DYSERYTHROPOIETIC, TYPE IVA	—	HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ANEMIA, DYSERYTHROPOIETIC, CONGENITAL	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL DYSERYTHROPOIETIC ANEMIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL DYSERYTHROPOIETIC ANEMIA TYPE IV	—	Disgenet, Orphanet Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMATOLOGIC DISEASES	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMATOLOGICAL DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
5q-syndrome	5q-syndrome	BEFREE	22965552		★☆☆☆☆ Found in Text Mining only
alpha-Thalassemia	alpha Thalassemia	BEFREE	24829204, 28342932		★☆☆☆☆ Found in Text Mining only
alpha^+^ Thalassemia	alpha Thalassemia	BEFREE	28342932		★☆☆☆☆ Found in Text Mining only
Anemia	Anemia	BEFREE	16728274, 19365556, 21778342, 23361909, 25585695, 28143845, 28180284, 29047116, 29230002		★☆☆☆☆ Found in Text Mining only
Anemia	Anemia	Pubtator	21778342, 25585695, 33686258	Associate	★☆☆☆☆ Found in Text Mining only
Anemia	Anemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Anemia Dyserythropoietic Congenital	Congenital dyserythropoietic anemia	Pubtator	21055716, 25724378, 29300242, 30872368, 30876823, 37084386	Associate	★☆☆☆☆ Found in Text Mining only
Anemia Hemolytic	Hemolytic anemia	Pubtator	24443441	Associate	★☆☆☆☆ Found in Text Mining only
Anemia Hemolytic Congenital Nonspherocytic	Hemolytic anemia	Pubtator	24443441, 25724378	Associate	★☆☆☆☆ Found in Text Mining only
Anemia hypochromic microcytic	Hypochromic microcytic anemia	Pubtator	25585695	Associate	★☆☆☆☆ Found in Text Mining only
Anemia Neonatal	Neonatal anemia	Pubtator	25724378	Associate	★☆☆☆☆ Found in Text Mining only
Anemia of inadequate production	Anemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Anemia Sickle Cell	Sickle cell anemia	Pubtator	22102705, 31134759	Associate	★☆☆☆☆ Found in Text Mining only
Anemia, Diamond-Blackfan	Anemia	BEFREE	22965552		★☆☆☆☆ Found in Text Mining only
Anemia, Hemolytic	Anemia	BEFREE	20691777, 24443441, 25976964, 30605837, 30921348		★☆☆☆☆ Found in Text Mining only
Anemia, Neonatal	Anemia	BEFREE	28143845		★☆☆☆☆ Found in Text Mining only
Anemia, Sickle Cell	Anemia	BEFREE	22102705, 23057549, 31134759		★☆☆☆☆ Found in Text Mining only
Autoimmune Diseases	Autoimmune Diseases	BEFREE	29728568		★☆☆☆☆ Found in Text Mining only
Avellino corneal dystrophy	Avellino Corneal Dystrophy	BEFREE	31126231		★☆☆☆☆ Found in Text Mining only
beta Thalassemia	beta Thalassemia	BEFREE	15352994, 24829204, 25082863, 29601850, 31115947, 8288615		★☆☆☆☆ Found in Text Mining only
beta Thalassemia	Beta thalassemia	Pubtator	15352994, 24829204, 25082863, 29601850, 31115947, 36939018, 39445566, 8288615	Associate	★☆☆☆☆ Found in Text Mining only
beta^+^ Thalassemia	beta Thalassemia	BEFREE	15352994, 24829204, 25082863, 29601850, 31115947, 8288615		★☆☆☆☆ Found in Text Mining only
Cataract	Cataract	Pubtator	34304709	Stimulate	★☆☆☆☆ Found in Text Mining only
cervical cancer	Cervical Cancer	BEFREE	25119587, 30132534		★☆☆☆☆ Found in Text Mining only
Cervix carcinoma	Cervix carcinoma	BEFREE	25119587, 30132534		★☆☆☆☆ Found in Text Mining only
Congenital dyserythropoietic anemia	Congenital dyserythropoietic anemia	BEFREE	21055716, 23522491, 30872368, 30876823, 31126231, 31818881		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital dyserythropoietic anemia	Congenital dyserythropoietic anemia	GENOMICS_ENGLAND_DG	21055716, 29200155		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital dyserythropoietic anemia	Congenital dyserythropoietic anemia	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital dyserythropoietic anemia type IV	Congenital dyserythropoietic anemia	UNIPROT_DG	21055716, 25585695		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital dyserythropoietic anemia type IV	Congenital dyserythropoietic anemia	GENOMICS_ENGLAND_DG	21055716, 29200155		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital dyserythropoietic anemia type IV	Congenital dyserythropoietic anemia	BEFREE	23522491, 25724378, 25976964, 27708211, 29200155, 29300242, 31126231, 31818881		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital dyserythropoietic anemia type IV	Congenital dyserythropoietic anemia	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital dyserythropoietic anemia type IV	Congenital dyserythropoietic anemia	ORPHANET_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital dyserythropoietic anemia type IV	Congenital dyserythropoietic anemia	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital dyserythropoietic anemia, type I	Congenital dyserythropoietic anemia	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Congenital dyserythropoietic anemia, type II	Congenital dyserythropoietic anemia	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Congenital dyserythropoietic anemia, type III	Anemia	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Corneal dystrophy Avellino type	Corneal dystrophy	Pubtator	21055716	Associate	★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Erythroblastosis Fetal	Fetal erythroblastosis	Pubtator	25724378	Associate	★☆☆☆☆ Found in Text Mining only
Erythroid hyperplasia	Erythroid hyperplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Glycogen Storage Disease XII	Glycogen storage disease	Pubtator	29700354, 30529538	Associate	★☆☆☆☆ Found in Text Mining only
Hematological Disease	Hematological Disease	CTD_human_DG	20676099		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hematological Disease	Hematological Disease	BEFREE	25976964		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hemoglobin C Disease	Hemoglobin c disease	Pubtator	24443441, 36939018	Associate	★☆☆☆☆ Found in Text Mining only
Hemoglobin E disease	Hemoglobin E Disease	BEFREE	25694242		★☆☆☆☆ Found in Text Mining only
Hemoglobin F Disease	Hemoglobinopathy	BEFREE	20676099, 23161389		★☆☆☆☆ Found in Text Mining only
Hemoglobin F Disease	Hemoglobinopathy	ORPHANET_DG	20676099		★☆☆☆☆ Found in Text Mining only
Hemoglobin H Disease	Hemoglobin H Disease	BEFREE	24930900		★☆☆☆☆ Found in Text Mining only
Hemoglobinopathies	Hemoglobinopathy	BEFREE	10688844, 25082863, 26794457, 27282573, 27708211, 28369821, 29420372, 30529538		★☆☆☆☆ Found in Text Mining only
Hemoglobinopathies	Hemoglobinopathy	Pubtator	21220744, 25082863, 26840243, 30529538	Associate	★☆☆☆☆ Found in Text Mining only
Hereditary persistence of fetal hemoglobin-beta-thalassemia syndrome	Hereditary Persistence Of Fetal Hemoglobin-Beta-Thalassemia Syndrome	Orphanet			★☆☆☆☆ Found in Text Mining only
Hereditary persistence of fetal hemoglobin-sickle cell disease syndrome	Hereditary Persistence Of Fetal Hemoglobin-Sickle Cell Disease Syndrome	Orphanet			★☆☆☆☆ Found in Text Mining only
Hereditary spherocytosis	Hereditary Spherocytosis	BEFREE	20691777		★☆☆☆☆ Found in Text Mining only
Hydrops Fetalis	Hydrops Fetalis	BEFREE	25724378, 31134759		★☆☆☆☆ Found in Text Mining only
Hydrops Fetalis	Hydrops fetalis	Pubtator	25724378, 29300242, 31134759	Associate	★☆☆☆☆ Found in Text Mining only
Hydrops Fetalis	Hydrops Fetalis	GENOMICS_ENGLAND_DG	28361594		★☆☆☆☆ Found in Text Mining only
Hydrops Fetalis	Hydrops Fetalis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hyperbilirubinemia	Hyperbilirubinemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Juvenile Myelomonocytic Leukemia	Myelomonocytic Leukemia	BEFREE	28749240		★☆☆☆☆ Found in Text Mining only
leukemia	Leukemia	BEFREE	29700354		★☆☆☆☆ Found in Text Mining only
Leukemia	Leukemia	Pubtator	29700354, 30850577	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia Myeloid Acute	Myeloid leukemia	Pubtator	12417757, 19097174	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia Myelomonocytic Juvenile	Myelomonocytic leukemia	Pubtator	28749240	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia, Myelocytic, Acute	Leukemia	BEFREE	19097174		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	29700354, 29728568		★☆☆☆☆ Found in Text Mining only
Malignant tumor of cervix	Cervical Tumor	BEFREE	25119587, 30132534		★☆☆☆☆ Found in Text Mining only
Microcytic hypochromic anemia (disorder)	Anemia	BEFREE	25585695		★☆☆☆☆ Found in Text Mining only
Myelodysplastic Syndrome with Isolated del(5q)	Myelodysplastic syndrome	BEFREE	22965552		★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	34669363	Stimulate	★☆☆☆☆ Found in Text Mining only
Thalassemia	Thalassemia	Pubtator	15352994, 21821711, 24829204	Associate	★☆☆☆☆ Found in Text Mining only
Urinary Bladder Neoplasms	Urinary bladder neoplasms	Pubtator	39376007	Associate	★☆☆☆☆ Found in Text Mining only
Uterine Cervical Neoplasms	Uterine neoplasm	Pubtator	30132534, 34669363	Associate	★☆☆☆☆ Found in Text Mining only