KLF1

KLF transcription factor 1, the group of Kruppel like factors|Zinc fingers C2H2-type

Basic information

Region (hg38): 19:12884422-12887201

Links

ENSG00000105610 ∙ NCBI:10661 ∙ OMIM:600599 ∙ HGNC:6345 ∙ Uniprot:Q13351 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital dyserythropoietic anemia type 4 (Definitive), mode of inheritance: AD
• hereditary persistence of fetal hemoglobin-beta-thalassemia syndrome (Supportive), mode of inheritance: AD
• hereditary persistence of fetal hemoglobin-sickle cell disease syndrome (Supportive), mode of inheritance: AR
• congenital dyserythropoietic anemia type 4 (Supportive), mode of inheritance: AD
• congenital dyserythropoietic anemia type 4 (Moderate), mode of inheritance: AD
• congenital dyserythropoietic anemia type 4 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Anemia, dyserythropoietic congenital, type IV; Blood group, Lutheran inhibitor	AD/BG	Hematologic	Treatments (including regular RBC transfusions and splenectomy) may be beneficial; Variants associated with a blood group may be important in specific situations (eg, related to transfusion)	Hematologic	1659863; 7680924; 7521883; 17319831; 18487511; 21055716; 20676099; 21531944; 21821711; 21273267; 22093801; 22102705

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KLF1 gene.

• not provided (4 variants)
• Congenital dyserythropoietic anemia type 4 (1 variants)
• BLOOD GROUP--LUTHERAN INHIBITOR;Congenital dyserythropoietic anemia type 4;Fetal hemoglobin quantitative trait locus 6 (1 variants)
• BLOOD GROUP--LUTHERAN INHIBITOR (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KLF1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	26	2	30
missense	2		47	4	6	59
nonsense	1		1			2
start loss			1			1
frameshift	1					1
inframe indel			1			1
splice donor/acceptor (+/-2bp)		2				2
splice region				3		3
non coding			5	6	8	19
Total	4	2	57	36	16

Variants in KLF1

This is a list of pathogenic ClinVar variants found in the KLF1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-12884431-G-C		Congenital dyserythropoietic anemia type 4	Benign (Jan 13, 2018)
19-12884518-G-C		Congenital dyserythropoietic anemia type 4	Uncertain significance (Jan 12, 2018)
19-12884573-C-G		Congenital dyserythropoietic anemia type 4	Uncertain significance (Jan 13, 2018)
19-12884574-T-C		Congenital dyserythropoietic anemia type 4	Uncertain significance (Jan 13, 2018)
19-12884589-C-T		Congenital dyserythropoietic anemia type 4	Benign (Jun 20, 2021)
19-12884594-T-C		Congenital dyserythropoietic anemia type 4	Benign (Jan 12, 2018)
19-12884608-G-A		Congenital dyserythropoietic anemia type 4	Benign (Jun 20, 2021)
19-12884622-G-A		Congenital dyserythropoietic anemia type 4	Uncertain significance (Jan 12, 2018)
19-12884631-G-A		Congenital dyserythropoietic anemia type 4	Benign (Jan 13, 2018)
19-12884700-C-T		Congenital dyserythropoietic anemia type 4	Benign (Jan 13, 2018)
19-12884863-A-T		Congenital dyserythropoietic anemia type 4	Benign (Jan 13, 2018)
19-12884883-G-A		Congenital dyserythropoietic anemia type 4	Uncertain significance (Jan 13, 2018)
19-12884895-C-T		BLOOD GROUP--LUTHERAN INHIBITOR	Uncertain significance (Dec 23, 2023)
19-12884897-C-T			Likely benign (Oct 03, 2022)
19-12884903-G-T		BLOOD GROUP--LUTHERAN INHIBITOR	Pathogenic (Jan 01, 2013)
19-12884910-G-A			Uncertain significance (Sep 11, 2023)
19-12884915-G-A			Likely benign (Aug 14, 2018)
19-12884938-G-A		Congenital dyserythropoietic anemia type 4	Uncertain significance (Jan 12, 2018)
19-12884948-C-G			Uncertain significance (Jul 07, 2023)
19-12884949-T-A			Likely benign (May 01, 2022)
19-12884950-G-C			Uncertain significance (May 12, 2022)
19-12884952-C-T			Likely pathogenic (-)
19-12884955-C-T		Inborn genetic diseases • KLF1-related disorder	Uncertain significance (Oct 10, 2023)
19-12884958-A-G		Congenital dyserythropoietic anemia type 4	Uncertain significance (Jan 13, 2018)
19-12884962-G-A		Congenital dyserythropoietic anemia type 4;FETAL HEMOGLOBIN QUANTITATIVE TRAIT LOCUS 6;BLOOD GROUP--LUTHERAN INHIBITOR	Pathogenic (-)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KLF1	protein_coding	protein_coding	ENST00000264834	3	2759

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000358	0.844	125626	0	21	125647	0.0000836

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.851	171	205	0.833	0.0000104	2198
Missense in Polyphen		72	93.379	0.77105		967
Synonymous	0.613	89	96.7	0.921	0.00000510	795
Loss of Function	1.26	7	11.7	0.601	5.05e-7	118

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000161	0.000152
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000132	0.000123
Middle Eastern	0.00	0.00
South Asian	0.000134	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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 a preferential activator of this gene. Furthermore, it binds to the BCL11A promoter and activates expression of BCL11A, which in turn represses the HBG1 and HBG2 genes. This dual activity ensures that, in most adults, fetal hemoglobin levels are low. Able to activate CD44 and AQP1 promoters. When sumoylated, acts as a transcriptional repressor by promoting interaction with CDH2/MI2beta and also represses megakaryocytic differentiation. {ECO:0000250|UniProtKB:P46099, ECO:0000269|PubMed:25585695}.
• Disease: DISEASE: Anemia, congenital dyserythropoietic, 4 (CDAN4) [MIM:613673]: A blood disorder characterized by ineffective erythropoiesis and hemolysis resulting in anemia. Circulating erythroblasts and erythroblasts in the bone marrow show various morphologic abnormalities. Affected individuals with CDA4 also have increased levels of fetal hemoglobin. {ECO:0000269|PubMed:21055716, ECO:0000269|PubMed:25585695}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Hematopoietic Stem Cell Differentiation (Consensus)

Recessive Scores

• pRec: 0.134

Haploinsufficiency Scores

• pHI: 0.793
• hipred: N
• hipred_score: 0.461
• ghis: 0.400

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.929

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Klf1
• Phenotype: homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; renal/urinary system phenotype; immune system phenotype; liver/biliary system phenotype; embryo phenotype

Gene ontology

• Biological process: regulation of transcription, DNA-templated;regulation of transcription by RNA polymerase II;erythrocyte differentiation;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;maternal process involved in female pregnancy;cellular response to peptide
• Cellular component: nuclear chromatin;nucleus;nucleoplasm
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity;protein binding;transcription regulatory region DNA binding;metal ion binding