CLTCL1

Chr 22

clathrin heavy chain like 1

Also known as: CHC22, CLH22, CLTCL, CLTD

NCBI Gene: 8218ENSG00000070371UniProt: P53675

This gene is a member of the clathrin heavy chain family and encodes a major protein of the polyhedral coat of coated pits and vesicles. Chromosomal aberrations involving this gene are associated with meningioma, DiGeorge syndrome, and velo-cardio-facial syndrome. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2009]

569
ClinVar variants
210
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CLTCL1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
210 Pathogenic / Likely Pathogenic· 282 VUS of 569 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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.
0.98LOEUF
pLI 0.000
Z-score 1.68
OE 0.80 (0.66–0.98)
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.
0.78Z-score
OE missense 0.93 (0.88–0.98)
840 obs / 905.8 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.0.80 (0.66–0.98)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.93 (0.88–0.98)
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.0.95
0≤1.21.6
LoF obs/exp: 66 / 82.5Missense obs/exp: 840 / 905.8Syn Z: 0.77

ClinVar Variant Classifications

569 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic204
Likely Pathogenic6
VUS282
Likely Benign44
Benign28
Conflicting5
204
Pathogenic
6
Likely Pathogenic
282
VUS
44
Likely Benign
28
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
204
0
204
Likely Pathogenic
0
0
6
0
6
VUS
2
257
23
0
282
Likely Benign
0
15
5
24
44
Benign
1
17
4
6
28
Conflicting
—5
Total328924230569

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.

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — CLTCL1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A novel prognostic signature related to programmed cell death in osteosarcoma.
Jiang YC et al.·Front Immunol
2024
Diagnosis of prenatal 22q11.2 duplication syndrome: a two-case study.
Li H et al.·J Genet
2023Case report
New Mendelian Disorders of Painlessness.
Nahorski MS et al.·Trends Neurosci
2015Review
Candidate genes of oculo-auriculo-vertebral spectrum in 22q region: A systematic review.
Glaeser AB et al.·Am J Med Genet A
2020Review
Genetic characterisation of 22q11.2 variations and prevalence in patients with congenital heart disease.
Hou HT et al.·Arch Dis Child
2020Cohort
Sacral agenesis: a pilot whole exome sequencing and copy number study.
Porsch RM et al.·BMC Med Genet
2016
A Genome-Wide Knockout Screen in Human Macrophages Identified Host Factors Modulating Salmonella Infection.
Yeung ATY et al.·mBio
2019
Whole-exome sequencing and homozygosity analysis implicate depolarization-regulated neuronal genes in autism.
Chahrour MH et al.·PLoS Genet
2012
A novel disorder reveals clathrin heavy chain-22 is essential for human pain and touch development.
Nahorski MS et al.·Brain
2015
Leveraging diverse cell death patterns in osteosarcoma patients and identification of the function of FADS2 in osteosarcoma cells.
Bai G et al.·Sci Rep
2025Cohort
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