CLTCL1

Chr 22

clathrin heavy chain like 1

Also known as: CHC22, CLH22, CLTCL, CLTD

NCBI Gene: 8218ENSG00000070371UniProt: P53675OMIM: 601273

CLTCL1 encodes a clathrin heavy chain that forms the polyhedral coat of coated pits and vesicles, linking clathrin lattices to the plasma membrane and trans-Golgi network for intracellular transport. Chromosomal aberrations involving this gene are associated with meningioma, DiGeorge syndrome, and velo-cardio-facial syndrome. The gene is not highly constrained against loss-of-function variants, and a GeneReviews entry provides additional clinical guidance.

GeneReviewsOMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.98
Clinical Summary— CLTCL1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
192 unique Pathogenic / Likely Pathogenic· 214 VUS of 499 total submissions
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — CLTCL1
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
0.98LOEUF
pLI 0.000
Z-score 1.68
OE 0.80 (0.66–0.98)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.78Z-score
OE missense 0.93 (0.88–0.98)
840 obs / 905.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.80 (0.66–0.98)
0≤0.351.4
Missense OE0.93 (0.88–0.98)
0≤0.61.4
Synonymous OE0.95
0≤1.21.6
LoF obs/exp: 66 / 82.5Missense obs/exp: 840 / 905.8Syn Z: 0.77
DN
0.6161th %ile
GOF
0.4776th %ile
LOF
0.3744th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

499 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic186
Likely Pathogenic6
VUS214
Likely Benign36
Benign23
Conflicting3
186
Pathogenic
6
Likely Pathogenic
214
VUS
36
Likely Benign
23
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
186
0
186
Likely Pathogenic
0
0
6
0
6
VUS
4
194
16
0
214
Likely Benign
0
13
3
20
36
Benign
2
15
2
4
23
Conflicting
—3
Total622221324468

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

View in ClinVar →

Protein Context — Lollipop Plot

CLTCL1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
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