KLHDC4

Chr 16

kelch domain containing 4

NCBI Gene: 54758ENSG00000104731UniProt: Q8TBB5
0
Active trials
51
Pathogenic / LP
234
ClinVar variants
4
Pubs (1 yr)
-2.6
Missense Z
1.86
LOEUF
Clinical Summary— KLHDC4
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
51 Pathogenic / Likely Pathogenic· 169 VUS of 234 total submissions

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.
1.86LOEUF
pLI 0.000
Z-score -2.23
OE 1.47 (1.13–1.86)
Tolerant

Highly tolerant — LoF variants common in population

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.
-2.62Z-score
OE missense 1.40 (1.30–1.51)
468 obs / 333.5 exp
Tolerant

Tolerant to missense variation

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.1.47 (1.13–1.86)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.40 (1.30–1.51)
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.1.42
0≤1.21.6
LoF obs/exp: 39 / 26.6Missense obs/exp: 468 / 333.5Syn Z: -4.09

ClinVar Variant Classifications

234 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic43
Likely Pathogenic8
VUS169
Likely Benign14
43
Pathogenic
8
Likely Pathogenic
169
VUS
14
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
43
0
43
Likely Pathogenic
0
0
8
0
8
VUS
0
144
25
0
169
Likely Benign
0
10
3
1
14
Benign
0
0
0
0
0
Total0154791234

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

View in ClinVar →

Protein Context — Lollipop Plot

KLHDC4 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 4 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients