KLF7

Chr 2

KLF transcription factor 7

Also known as: UKLF

NCBI Gene: 8609 ENSG00000118263 OMIM: 604865

KLF7 encodes a transcriptional factor containing C2H2 zinc fingers that plays a critical role in neuronal morphogenesis and survival of sensory neurons, while also regulating insulin sensitivity and adipogenesis. Mutations cause autosomal dominant developmental delay with variable intellectual disability and dysmorphic facies. This gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to be pathogenic.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a member of the Kruppel-like transcriptional regulator family. Members in this family regulate cell proliferation, differentiation and survival and contain three C2H2 zinc fingers at the C-terminus that mediate binding to GC-rich sites. This protein may contribute to the progression of type 2 diabetes by inhibiting insulin expression and secretion in pancreatic beta-cells and by deregulating adipocytokine secretion in adipocytes. A pseudogene of this gene is located on the long arm of chromosome 3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.24

Clinical Summary— KLF7

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 54 VUS of 82 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.24LOEUF

pLI 0.982

Z-score 3.24

OE 0.00 (0.00–0.24)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.30Z-score

OE missense 0.53 (0.45–0.63)

101 obs / 190.5 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.24)

0≤0.351.4

Missense OE?0.53 (0.45–0.63)

0≤0.61.4

Synonymous OE?1.14

0≤1.21.6

LoF obs/exp: 0 / 12.2Missense obs/exp: 101 / 190.5Syn Z: -1.01

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

moderateKLF7-related developmental disorderOTHERAD

This gene — mechanism propensity

0.3892th %ile

GOF

0.2994th %ile

LOF

0.83top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.24

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

82 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1

VUS54

Likely Benign11

Benign5

Conflicting1

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

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	1	0	0	1
VUS	2	51	1	0	54
Likely Benign	0	8	0	3	11
Benign	0	1	1	3	5
Conflicting	—				1
Total	2	61	2	6	72

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

View in ClinVar →

27 pathogenic / likely-pathogenic (of 29) ClinVar copy-number / structural variants overlap KLF7 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →