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…

LOFmechanismARLOEUF 0.651 OMIM phenotype

Clinical Summary— KCTD7

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Gene-Disease Validity (ClinGen)

progressive myoclonus epilepsy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

41 unique Pathogenic / Likely Pathogenic· 215 VUS of 475 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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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

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveKCTD7-related progressive myoclonic epilepsyLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6936th %ile

GOF

0.5856th %ile

LOF

0.2776th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

475 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21

Likely Pathogenic20

VUS215

Likely Benign168

Benign25

Conflicting24

Pathogenic

Likely Pathogenic

215

VUS

168

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	12	4	5	0	21
Likely Pathogenic	8	10	1	1	20
VUS	1	148	63	3	215
Likely Benign	0	0	76	92	168
Benign	0	0	23	2	25
Conflicting	—				24
Total	21	162	168	98	473

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

View in ClinVar →

18 pathogenic / likely-pathogenic (of 27) ClinVar copy-number / structural variants overlap KCTD7 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →