KCTD16

Chr 5

potassium channel tetramerization domain containing 16

NCBI Gene: 57528ENSG00000183775UniProt: Q68DU8

Predicted to enable G protein-coupled neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential; G protein-coupled neurotransmitter receptor activity involved in regulation of presynaptic membrane potential; and identical protein binding activity. Predicted to be involved in regulation of G protein-coupled receptor signaling pathway. Predicted to act upstream of or within behavioral fear response and memory. Predicted to be located in cell projection; plasma membrane; and synapse. Predicted to be part of receptor complex. Predicted to be active in postsynaptic membrane and presynaptic membrane. [provided by Alliance of Genome Resources, Jul 2025]

63
ClinVar variants
12
Pathogenic / LP
0.99
pLI score· haploinsufficient
0
Active trials
Clinical Summary— KCTD16
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
12 Pathogenic / Likely Pathogenic· 49 VUS of 63 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.20LOEUF
pLI 0.993
Z-score 3.58
OE 0.00 (0.00–0.20)
Highly constrained

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

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.
1.23Z-score
OE missense 0.78 (0.69–0.88)
191 obs / 245.3 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.0.00 (0.00–0.20)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.78 (0.69–0.88)
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.1.08
0≤1.21.6
LoF obs/exp: 0 / 14.9Missense obs/exp: 191 / 245.3Syn Z: -0.63

ClinVar Variant Classifications

63 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
VUS49
Likely Benign2
12
Pathogenic
49
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
12
0
12
Likely Pathogenic
0
0
0
0
0
VUS
0
45
4
0
49
Likely Benign
0
1
1
0
2
Benign
0
0
0
0
0
Total04617063

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

View in ClinVar →

Protein Context — Lollipop Plot

KCTD16 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The expanded clinical spectrum of anti-GABABR encephalitis and added value of KCTD16 autoantibodies.
van Coevorden-Hameete MH et al.·Brain
2019
Comprehensive analysis of KCTD family genes associated with hypoxic microenvironment and immune infiltration in lung adenocarcinoma.
Shi YX et al.·Sci Rep
2022
High grade gliomas in young children: The South Thames Neuro-Oncology unit experience and recent advances in molecular biology and targeted therapies.
Pearce J et al.·Pediatr Hematol Oncol
2021Review
Significance of achaete-scute complex homologue 1 (ASCL1) in pulmonary neuroendocrine carcinomas; RNA sequence analyses using small cell lung cancer cells and Ascl1-induced pulmonary neuroendocrine carcinoma cells.
Kudoh S et al.·Histochem Cell Biol
2020
Mechanistic Insights Into the Tumor-Driving and Diagnostic Roles of KCTD Family Genes in Ovarian Cancer: An Integrated In Silico and In Vitro Analysis.
Zhang L et al.·Cancer Med
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools