KCTD7

Chr 7AR

potassium channel tetramerization domain containing 7

Also known as: CLN14, EPM3

NCBI Gene: 154881 ENSG00000243335 UniProt: Q96MP8

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]

Primary Disease Associations & Inheritance

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

502

ClinVar variants

Pathogenic / LP

0.00

pLI score

Active trials

Clinical Summary— KCTD7

⚡

Population Constraint (gnomAD)

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

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ClinVar Variants

57 Pathogenic / Likely Pathogenic· 221 VUS of 502 total submissions

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Clinical Trials

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

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

0.65LOEUF

pLI 0.001

Z-score 2.90

OE 0.39 (0.24–0.65)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

1.47Z-score

OE missense 0.75 (0.67–0.84)

210 obs / 279.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.39 (0.24–0.65)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.75 (0.67–0.84)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.90

0≤1.21.6

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

ClinVar Variant Classifications

502 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic36

Likely Pathogenic21

VUS221

Likely Benign170

Benign25

Conflicting24

Pathogenic

Likely Pathogenic

221

VUS

170

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	6	4	26	0	36
Likely Pathogenic	6	8	6	1	21
VUS	1	142	75	3	221
Likely Benign	0	1	77	92	170
Benign	0	0	23	2	25
Conflicting	—				24
Total	13	155	207	98	497

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

View in ClinVar →

Protein Context — Lollipop Plot

KCTD7 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

KCTD7-related progressive myoclonic epilepsy

definitive

ARLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure

Dev. Disorders

G2P ↗

splice region variantmissense variantinframe deletioninframe insertionstop gained NMD triggeringframeshift variant NMD triggeringframeshift variant NMD escaping

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org