KLF13

protein-coding

KLF transcription factor 13, the group of Kruppel like factors|Zinc fingers C2H2-type

Gene summary

KLF13 belongs to a family of transcription factors that contain 3 classical zinc finger DNA-binding domains consisting of a zinc atom tetrahedrally coordinated by 2 cysteines and 2 histidines (C2H2 motif). These transcription factors bind to GC-rich sequences and related GT and CACCC boxes (Scohy et al., 2000 [PubMed 11087666]).[supplied by OMIM, Mar 2008]

MANE transcript

NM_015995.4

Inheritance

ClinVar variants

U:58B:13

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.2

Max pathogenic AF

—

Genomic locus

chr15:31,326,835-31,435,665

External References & Databases

Ensembl (ENSG00000169926)

Transcript & Mutation Effects

hg38 • Region Span ~108.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

congenital heart diseaseMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0005453

Submitter: ClinGen

*KLF13* was first reported in relation to autosomal dominant congenital heart disease in 2020 (Li et all.; PMID: 32293321). Four variants (missense, nonsense) that have been reported in four probands in three publications (PMID: 32293321, 33215447, 35369534) are included in this curation. The p.Glu124* and p.Glu144* were found to segregate in two respective families (PMID:33215447,35369534). This gene-disease relationship is also supported by protein interaction experimental evidence with *GATA4* and *TBX5*, which are two genes that have been definitively associated with isolated congenital heart disease (PMID: 17053787, 28164238).In summary, there is moderate evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged. This classification was approved by the ClinGen Congenital Heart Disease GCEP on the meeting date 2/12/2024 (SOP Version 10).

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KLF13 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 60

not providedTotal: 11

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015995.4. 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				9 clinvar	2 clinvar	11
missense			58 clinvar	2 clinvar		60
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	58	11	2	71

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015995.4	RefSeq	NP_057079.2	2	MANE Select
ENST00000307145.4	Ensembl	ENSP00000302456.3	2	MANE Select
NM_001302461.2	RefSeq	NP_001289390.1	2	Standard
ENST00000558844.1	Ensembl	ENSP00000452867.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription by RNA polymerase II
transcription by RNA polymerase II
negative regulation of cell population proliferation
negative regulation of erythrocyte differentiation
positive 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 activator activity, RNA polymerase II-specific
protein binding
metal ion binding

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000307145
Coding exons: 2
Length: 108811
Individuals with no LoFs: 120367
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 120369
p: 0.00000831

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.02	52	112	0.464	0.00000800	1809
Missense (PolyPhen)		2	6.6478	0.30085		86
Synonymous	-0.457	54	49.9	1.08	0.00000386	605
Loss of Function	1.68	1	5.08	0.197	2.20e-7	82

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000066	0.000066	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Represses transcription by binding to the BTE site, a GC-rich DNA element, in competition with the activator SP1. It also represses transcription by interacting with the corepressor Sin3A and HDAC1. Activates RANTES expression in T-cells. {ECO:0000269|PubMed:11477107}.;

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.493

Gene Damage Prediction

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