KLF10

Chr 8

KLF transcription factor 10

Also known as: EGR-alpha, EGRA, TIEG, TIEG1

NCBI Gene: 7071 ENSG00000155090 UniProt: Q13118 OMIM: 601878

KLF10 encodes a transcriptional repressor containing zinc finger domains that regulates circadian clock genes and metabolic pathways including gluconeogenesis and glycolysis. Mutations cause autosomal dominant early-onset severe obesity due to hyperphagia, as described in GeneReviews. The gene is not highly constrained against loss-of-function variants, with metabolic dysfunction being the primary clinical manifestation.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.86

Clinical Summary— KLF10

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Gene-Disease Validity (ClinGen)

hypertrophic cardiomyopathy · ADLimited

Limited evidence — not for standalone diagnostic reporting

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

174 VUS of 311 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — KLF10

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.86LOEUF

pLI 0.005

Z-score 1.93

OE 0.44 (0.24–0.86)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.39Z-score

OE missense 0.76 (0.68–0.85)

204 obs / 268.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.44 (0.24–0.86)

0≤0.351.4

Missense OE?0.76 (0.68–0.85)

0≤0.61.4

Synonymous OE?1.18

0≤1.21.6

LoF obs/exp: 6 / 13.7Missense obs/exp: 204 / 268.0Syn Z: -1.42

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

limitedKLF10-related hypertrophic cardiomyopathyOTHERAD

This gene — mechanism propensity

0.6258th %ile

GOF

0.2796th %ile

LOF

0.53top 25%

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

311 submitted variants in ClinVar

ClinVar

Classification Summary

VUS174

Likely Benign103

Benign26

174

VUS

103

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	6	163	3	2	174
Likely Benign	0	2	24	77	103
Benign	0	4	17	5	26
Total	6	169	44	84	303

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

41 pathogenic / likely-pathogenic (of 49) ClinVar copy-number / structural variants overlap KLF10 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →