KLF8

protein-coding

KLF transcription factor 8, the group of Kruppel like factors|Zinc fingers C2H2-type

Gene summary

This gene encodes a protein which is a member of the Sp/KLF family of transcription factors. Members of this family contain a C-terminal DNA-binding domain with three Kruppel-like zinc fingers. The encoded protein is thought to play an important role in the regulation of epithelial to mesenchymal transition, a process which occurs normally during development but also during metastasis. A pseudogene has been identified on chromosome 16. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2009]

MANE transcript

NM_007250.5

Inheritance

—

ClinVar variants

U:82B:14

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.63

Max pathogenic AF

—

Genomic locus

chrX:56,232,356-56,291,531

External References & Databases

Ensembl (ENSG00000102349)

Transcript & Mutation Effects

hg38 • Region Span ~59.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KLF8 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 41

not providedTotal: 12

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_007250.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			6 clinvar	8 clinvar		14
missense			58 clinvar	5 clinvar	1 clinvar	64
nonsense			7 clinvar			7
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			11 clinvar			11
Total	0	0	82	13	1	96

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 26 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_007250.5	RefSeq	NP_009181.2	6	MANE Select
ENST00000468660.6	Ensembl	ENSP00000417303.1	6	MANE Select
NM_001159296.2	RefSeq	NP_001152768.1	5	Standard
NM_001324099.1	RefSeq	NP_001311028.1	4	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
klf8	Danio rerio	Structure: cerebellar granule cell Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

klf8

Danio rerio

Structure: cerebellar granule cell

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signaling events mediated by focal adhesion kinase

Biological Process

negative regulation of transcription by RNA polymerase II
regulation of transcription by RNA polymerase II

Molecular Function

RNA polymerase II proximal promoter sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription repressor activity, RNA polymerase II-specific
metal ion binding

Cellular Component

nucleus
nucleoplasm
cytosol
aggresome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000468660
Coding exons: 6
Length: 55469
Individuals with no LoFs: 125707
Homozygous LoFs: 2
Heterozygous LoFs: 5
Defined: 125714
p: 0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.381	122	134	0.907	0.0000102	2341
Missense (PolyPhen)		21	28.239	0.74366		537
Synonymous	-0.229	47	45.0	1.04	0.00000302	727
Loss of Function	0.975	5	7.97	0.627	5.02e-7	169

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000081	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000074	0.000054	rare
Finnish	0.000064	0.000046	rare
European (Non-Finnish)	0.000038	0.000026	rare
South Asian	0	0.0	absent
Other	0.00023	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcriptional repressor and activator. Binds to CACCC- boxes promoter elements. Also binds the GT-box of cyclin D1 promoter and mediates cell cycle progression at G(1) phase as a downstream target of focal adhesion kinase (FAK). {ECO:0000269|PubMed:10756197, ECO:0000269|PubMed:12820964, ECO:0000269|PubMed:16617055}.;

Recessive Scores

pRec: 0.0677

Intolerance Scores

LoFtool: 0.398
RVIS EVS: 0.17
RVIS percentile EVS: 65.56

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

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