KCTD7

Chr 7AR

potassium channel tetramerization domain containing 7

Also known as: CLN14, EPM3

NCBI Gene: 154881 ENSG00000243335 UniProt: Q96MP8 OMIM: 611725

This gene encodes a member of the potassium channel tetramerization domain-containing protein family that may control excitability of cortical neurons. Mutations cause progressive myoclonic epilepsy-3 with or without intracellular inclusions, inherited in an autosomal recessive pattern. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.654), consistent with its role in neuronal excitability control.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the potassium channel tetramerization domain-containing protein family. Family members are identified on a structural basis and contain an amino-terminal domain similar to the T1 domain present in the voltage-gated potassium channel. Mutations in this gene have been associated with progressive myoclonic epilepsy-3. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Jan 2011]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Epilepsy, progressive myoclonic 3, with or without intracellular inclusionsMIM #611726

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · progressive myoclonus epilepsy · AR · ClinGen 2022

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.65

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — KCTD7

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?

0.65LOEUF

pLI 0.001

Z-score 2.90

OE 0.39 (0.24–0.65)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.47Z-score

OE missense 0.75 (0.67–0.84)

210 obs / 279.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.39 (0.24–0.65)

0≤0.351.4

Missense OE?0.75 (0.67–0.84)

0≤0.61.4

Synonymous OE?0.90

0≤1.21.6

LoF obs/exp: 10 / 25.9Missense obs/exp: 210 / 279.0Syn Z: 0.75

Background carrier burden — how many people carry a rare variant somewhere in KCTD7?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

517 rare PASS variants

Rare truncating (LoF)

1 in 1,900

54 rare PASS variants

Rare synonymous (reference)

1 in 510

119 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for KCTD7. 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 130	1 in 4,100
South Asian	~43k	1 in 92	1 in 960
Remaining (unassigned)	~30k	1 in 85	1 in 2,100
European (Finnish)	~27k	1 in 370	≈ 1 in 24,000
Admixed American	~22k	1 in 190	≈ 1 in 7,500
African / African American	~21k	1 in 100	1 in 620
East Asian	~20k	1 in 95	1 in 2,300
Ashkenazi Jewish	~13k	1 in 420	none seen
Middle Eastern	~2,884	1 in 100	≈ 1 in 2,700

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): 3 of 4 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 4.? see exons ↓