KLF10

Chr 8

KLF transcription factor 10

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

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.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
30
Pubs (1 yr)
41
P/LP submissions
0%
P/LP missense
0.86
LOEUF
DN
Mechanism· predicted
Clinical SummaryKLF10
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Gene-Disease Validity (ClinGen)
hypertrophic cardiomyopathy · ADLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
41 unique Pathogenic / Likely Pathogenic· 180 VUS of 358 total submissions
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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

Tolerant — LoF & missense variants common in population
LoF Constraint
0.86LOEUF
pLI 0.005
Z-score 1.93
OE 0.44 (0.240.86)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.39Z-score
OE missense 0.76 (0.680.85)
204 obs / 268.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.44 (0.240.86)
00.351.4
Missense OE0.76 (0.680.85)
00.61.4
Synonymous OE1.18
01.21.6
LoF obs/exp: 6 / 13.7Missense obs/exp: 204 / 268.0Syn Z: -1.42
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedKLF10-related hypertrophic cardiomyopathyOTHERAD
DN
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

358 submitted variants in ClinVar

Classification Summary

Pathogenic39
Likely Pathogenic2
VUS180
Likely Benign103
Benign26
39
Pathogenic
2
Likely Pathogenic
180
VUS
103
Likely Benign
26
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
39
0
39
Likely Pathogenic
0
0
2
0
2
VUS
4
161
13
2
180
Likely Benign
0
2
24
77
103
Benign
0
4
17
5
26
Total41679584350

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

View in ClinVar →

Protein Context — Lollipop Plot

KLF10 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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