KCTD12

Chr 13

potassium channel tetramerization domain containing 12

Also known as: C13orf2, PFET1, PFETIN

NCBI Gene: 115207 ENSG00000178695 UniProt: Q96CX2

KCTD12 encodes an auxiliary subunit of GABA-B receptors that regulates receptor pharmacology, kinetics, and G-protein signaling by accelerating onset and promoting desensitization. Mutations cause neurodevelopmental disorders with epilepsy, developmental delay, and intellectual disability, typically with autosomal recessive inheritance. The gene shows tolerance to loss-of-function variants, suggesting that complete loss of function may be compatible with survival but still pathogenic.

ResearchSummary from RefSeq, UniProt

Enables identical protein binding activity. Predicted to be involved in regulation of G protein-coupled receptor signaling pathway. Predicted to be part of signaling receptor complex. Predicted to be active in GABA-ergic synapse; postsynaptic membrane; and presynaptic active zone membrane. [provided by Alliance of Genome Resources, Jun 2026]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.01

LOEUF

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

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.01LOEUF

pLI 0.062

Z-score 1.57

OE 0.39 (0.18–1.01)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.76Z-score

OE missense 0.84 (0.73–0.96)

145 obs / 173.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.39 (0.18–1.01)

0≤0.351.4

Missense OE?0.84 (0.73–0.96)

0≤0.61.4

Synonymous OE?1.36

0≤1.21.6

LoF obs/exp: 3 / 7.7Missense obs/exp: 145 / 173.2Syn Z: -2.54

Background carrier burden — how many people carry a rare variant somewhere in KCTD12?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 250

475 rare PASS variants

Rare truncating (LoF)

1 in 5,700

46 rare PASS variants

Rare synonymous (reference)

1 in 140

281 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for KCTD12. 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 330	1 in 5,700
South Asian	~43k	1 in 130	1 in 2,300
Remaining (unassigned)	~30k	1 in 230	≈ 1 in 30,000
European (Finnish)	~27k	1 in 360	1 in 3,000
Admixed American	~22k	1 in 210	≈ 1 in 6,900
African / African American	~21k	1 in 250	≈ 1 in 9,200
East Asian	~20k	1 in 150	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 850	none seen
Middle Eastern	~2,884	1 in 140	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): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓