KLF12

Chr 13

KLF transcription factor 12

Also known as: AP-2rep, AP2REP, HSPC122

NCBI Gene: 11278 ENSG00000118922 UniProt: Q9Y4X4

The protein is a transcriptional repressor that belongs to the Kruppel-like zinc finger family and specifically represses AP-2 alpha gene expression by binding to its promoter. This gene is highly constrained against loss-of-function variants (pLI 0.98, LOEUF 0.29), indicating that mutations are likely to cause severe developmental consequences. However, no specific Mendelian diseases have been definitively associated with KLF12 mutations in current clinical databases.

ResearchSummary from RefSeq, UniProt

Activator protein-2 alpha (AP-2 alpha) is a developmentally-regulated transcription factor and important regulator of gene expression during vertebrate development and carcinogenesis. The protein encoded by this gene is a member of the Kruppel-like zinc finger protein family and can repress expression of the AP-2 alpha gene by binding to a specific site in the AP-2 alpha gene promoter. Repression by the encoded protein requires binding with a corepressor, CtBP1. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.29

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.29LOEUF

pLI 0.981

Z-score 3.53

OE 0.06 (0.02–0.29)

Highly constrained

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

Missense Constraint?

1.79Z-score

OE missense 0.68 (0.60–0.77)

167 obs / 246.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.06 (0.02–0.29)

0≤0.351.4

Missense OE?0.68 (0.60–0.77)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 1 / 16.5Missense obs/exp: 167 / 246.2Syn Z: -0.64

Background carrier burden — how many people carry a rare variant somewhere in KLF12?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 140

442 rare PASS variants

Rare truncating (LoF)

1 in 14,000

26 rare PASS variants

Rare synonymous (reference)

1 in 130

224 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for KLF12. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 270	1 in 14,000
South Asian	~43k	1 in 130	≈ 1 in 21,000
Remaining (unassigned)	~30k	1 in 180	≈ 1 in 15,000
European (Finnish)	~27k	1 in 490	none seen
Admixed American	~22k	1 in 140	≈ 1 in 5,700
African / African American	~21k	1 in 150	≈ 1 in 5,500
East Asian	~20k	1 in 170	none seen
Ashkenazi Jewish	~13k	1 in 1,600	≈ 1 in 6,400
Middle Eastern	~2,884	1 in 190	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 5 of 7 coding exons well covered in gnomAD exomes; exons 2, 6 marginal. Genomes: all 7.? see exons ↓