CALD1

Chr 7

caldesmon 1

Also known as: CDM, H-CAD, HCAD, L-CAD, LCAD, NAG22, h-CD

NCBI Gene: 800ENSG00000122786UniProt: Q05682

This gene encodes a calmodulin- and actin-binding protein that plays an essential role in the regulation of smooth muscle and nonmuscle contraction. The conserved domain of this protein possesses the binding activities to Ca(2+)-calmodulin, actin, tropomyosin, myosin, and phospholipids. This protein is a potent inhibitor of the actin-tropomyosin activated myosin MgATPase, and serves as a mediating factor for Ca(2+)-dependent inhibition of smooth muscle contraction. Alternative splicing of this gene results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

155
ClinVar variants
33
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— CALD1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
33 Pathogenic / Likely Pathogenic· 106 VUS of 155 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.
0.26LOEUF
pLI 0.999
Z-score 5.46
OE 0.13 (0.07–0.26)
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.
0.80Z-score
OE missense 0.89 (0.82–0.97)
387 obs / 434.0 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.0.13 (0.07–0.26)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.82–0.97)
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.0.84
0≤1.21.6
LoF obs/exp: 6 / 46.0Missense obs/exp: 387 / 434.0Syn Z: 1.52

ClinVar Variant Classifications

155 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic32
Likely Pathogenic1
VUS106
Likely Benign10
Benign6
32
Pathogenic
1
Likely Pathogenic
106
VUS
10
Likely Benign
6
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
32
0
32
Likely Pathogenic
0
0
1
0
1
VUS
0
101
5
0
106
Likely Benign
0
6
1
3
10
Benign
0
6
0
0
6
Total0113393155

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

View in ClinVar →

Protein Context — Lollipop Plot

CALD1 · 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
CALDESMON 1; CALD1
MIM #114213 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Joint analysis of single-cell RNA sequencing and bulk transcriptome reveals the heterogeneity of the urea cycle of astrocytes in glioblastoma.
Tong M et al.·Neurobiol Dis
2025
Variants in CALD1, ESRP1, and RBFOX1 are associated with orofacial cleft risk.
Carlson JC et al.·PLoS Genet
2025Meta-analysis
Oligosarcomas, IDH-mutant are distinct and aggressive.
Suwala AK et al.·Acta Neuropathol
2022
Discovery of protein lactylation-associated biomarkers and their potential pathogenic mechanisms in recurrent spontaneous abortion.
Yan X et al.·Int J Biol Macromol
2025Functional
Endothelin-1 potentiated constriction in preeclampsia placental veins: Role of ETAR/ETBR/CaV1.2/CALD1.
Su H et al.·Placenta
2024
An integrated approach for key gene selection and cancer phenotype classification: Improving diagnosis and prediction.
Rahaman MM et al.·Comput Biol Med
2025
Upregulation of CALD1 predicted a poor prognosis for platinum-treated ovarian cancer and revealed it as a potential therapeutic resistance target.
Li W et al.·BMC Genomics
2024
Identification of novel biomarkers associated with immune infiltration in major depression disorder and atopic dermatitis.
Jiang H et al.·Arch Dermatol Res
2025
The contribution of 7q33 copy number variations for intellectual disability.
Lopes F et al.·Neurogenetics
2018
Identification of lactylation-associated fibroblast subclusters predicting prognosis and cancer immunotherapy response in colon cancer.
Liang L et al.·Gene
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