KLHDC10

Chr 7

kelch domain containing 10

Also known as: PNAS-138, slim

NCBI Gene: 23008ENSG00000128607UniProt: Q6PID8

Enables ubiquitin-like ligase-substrate adaptor activity. Involved in rescue of stalled ribosome and ubiquitin-dependent protein catabolic process via the C-end degron rule pathway. Located in nucleoplasm. Is active in Cul2-RING ubiquitin ligase complex and cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

0
Active trials
23
Pathogenic / LP
54
ClinVar variants
0
Pubs (1 yr)
3.4
Missense Z· constrained
0.35
LOEUF
Clinical Summary— KLHDC10
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.93). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
23 Pathogenic / Likely Pathogenic· 31 VUS of 54 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.35LOEUF
pLI 0.926
Z-score 3.99
OE 0.15 (0.07–0.35)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
3.41Z-score
OE missense 0.38 (0.32–0.45)
90 obs / 237.9 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.15 (0.07–0.35)
0≤0.351.4
Missense OE0.38 (0.32–0.45)
0≤0.61.4
Synonymous OE0.93
0≤1.21.6
LoF obs/exp: 4 / 25.9Missense obs/exp: 90 / 237.9Syn Z: 0.49
LOF
DN
0.4587th %ile
GOF
0.4579th %ile
LOF
0.71top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.35

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

54 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic1
VUS31
22
Pathogenic
1
Likely Pathogenic
31
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
22
0
22
Likely Pathogenic
0
0
1
0
1
VUS
0
27
4
0
31
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total02727054

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

View in ClinVar →

KLHDC10 · 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 5 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