KLF10

protein-coding

KLF transcription factor 10, the group of Kruppel like factors|Zinc fingers C2H2-type

Gene summary

This gene encodes a member of a family of proteins that feature C2H2-type zinc finger domains. The encoded protein is a transcriptional repressor that acts as an effector of transforming growth factor beta signaling. Activity of this protein may inhibit the growth of cancers, particularly pancreatic cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2013]

Previous symbols:

TIEG

MANE transcript

NM_005655.4

Inheritance

ClinVar variants

U:175B:87

Top phenotype

KLF10-related disorder

gnomAD constraint

pLI —, LoF o/e 0.44

Max pathogenic AF

—

Genomic locus

chr8:102,648,784-102,655,725

External References & Databases

Ensembl (ENSG00000155090)

Transcript & Mutation Effects

hg38 • Region Span ~6.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

familial hypertrophic cardiomyopathyLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0024573

Submitter: G2P

hypertrophic cardiomyopathyLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0005045

Submitter: PanelApp Australia

hypertrophic cardiomyopathyLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0005045

Submitter: ClinGen

The *KLF10* gene has been associated with hypertrophic cardiomyopathy (HCM) in one cohort study that identified 6 missense variants in 6 probands with HCM (Bos et al. PMID 22234868). No segregation data exists. The functional data reported for these variants is not strongly supportive of pathogenicity (PMID 22234868). One case control study identified no excess variants in HCM patients (Walsh et al. 28082330). The mechanism for disease is not clear but predicted to be loss of function based on experimental studies. This gene-disease association is supported by expression data (Subramaniam et al., 1995 PMID: 8532536; Jiang et al., 2010 PMID: 20201061, Fagerberg et al. PMID 24309898), functional alteration in non patient cells (Li et al., 2015 PMID: 26252173), and model organism studies (Rajamannan et al., 2007 PMID: 16888812). KLF10-/- knockout mice showed left ventricular hypertrophy, fibrosis and myofibrillar disarray. In summary, there is LIMITED evidence to support this gene-disease association. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease association. This classification was originally approved by the ClinGen Hypertrophic Cardiomyopathy Gene Curation Expert Panel on August 1, 2017. This gene-disease relationship was reevaluated on September 14, 2022 by the Hereditary Cardiovascular Disorders GCEP. As a result of this reevaluation, the classification did not change.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KLF10 variants in ClinVar

4 Conditions Cataloged

not providedTotal: 268

not specifiedTotal: 54

KLF10-related disorderTotal: 8

KLF10-related hypertrophic cardiomyopathyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005655.4. 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			4 clinvar	77 clinvar	3 clinvar	84
missense			164 clinvar	3 clinvar	4 clinvar	171
nonsense			1 clinvar			1
start loss						0
frameshift			4 clinvar			4
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	175	80	7	262

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005655.4	RefSeq	NP_005646.1	4	MANE Select
ENST00000285407.11	Ensembl	ENSP00000285407.6	4	MANE Select
NM_001032282.4	RefSeq	NP_001027453.1	4	Standard
ENST00000395884.3	Ensembl	ENSP00000379222.3	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

TGF-beta Signaling Pathway
TGF_beta_Receptor

Biological Process

negative regulation of transcription by RNA polymerase II
skeletal system development
regulation of transcription by RNA polymerase II
transforming growth factor beta receptor signaling pathway
cell-cell signaling

Molecular Function

RNA polymerase II proximal promoter sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
core promoter sequence-specific DNA binding
DNA-binding transcription activator activity, RNA polymerase II-specific
DNA-binding transcription factor activity

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000285407
Coding exons: 4
Length: 7124
Individuals with no LoFs: 125737
Homozygous LoFs: 0
Heterozygous LoFs: 11
Defined: 125748
p: 0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.39	204	268	0.761	0.0000138	3144
Missense (PolyPhen)		27	78.134	0.34556		895
Synonymous	-1.42	117	99.1	1.18	0.00000528	977
Loss of Function	1.93	6	13.7	0.438	6.62e-7	186

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcriptional repressor which binds to the consensus sequence 5'-GGTGTG-3'. Plays a role in the regulation of the circadian clock; binds to the GC box sequence in the promoter of the core clock component ARTNL/BMAL1 and represses its transcriptional activity. Regulates the circadian expression of genes involved in lipogenesis, gluconeogenesis, and glycolysis in the liver. Represses the expression of PCK2, a rate-limiting step enzyme of gluconeogenesis (By similarity). May play a role in the cell cycle regulation. {ECO:0000250|UniProtKB:O89091, ECO:0000269|PubMed:8584037}.;

Recessive Scores

pRec: 0.173

Intolerance Scores

LoFtool: 0.446
RVIS EVS: 0.37
RVIS percentile EVS: 75.43

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): K
Indispensability pred.: E
Indispensability score: 0.868

Gene Damage Prediction

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