CALML3

Chr 10

calmodulin like 3

Also known as: CLP

CALML3 encodes a calcium-binding protein that functions as a specific light chain of unconventional myosin-10 and enhances its translation, possibly by acting as a chaperone for the emerging heavy chain protein. Mutations cause autosomal recessive congenital cataracts affecting the eye. The gene shows low constraint to loss-of-function variation, consistent with a recessive inheritance pattern.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.90
Clinical SummaryCALML3
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
26 unique Pathogenic / Likely Pathogenic· 37 VUS of 67 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.90LOEUF
pLI 0.001
Z-score -0.43
OE 1.26 (0.571.90)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.94Z-score
OE missense 0.76 (0.640.90)
90 obs / 118.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.26 (0.571.90)
00.351.4
Missense OE0.76 (0.640.90)
00.61.4
Synonymous OE0.82
01.21.6
LoF obs/exp: 4 / 3.2Missense obs/exp: 90 / 118.7Syn Z: 1.05
DN
0.86top 5%
GOF
0.5758th %ile
LOF
0.2189th %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

67 submitted variants in ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic2
VUS37
Likely Benign2
Benign1
24
Pathogenic
2
Likely Pathogenic
37
VUS
2
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
24
0
24
Likely Pathogenic
0
0
2
0
2
VUS
0
25
12
0
37
Likely Benign
0
1
1
0
2
Benign
0
0
1
0
1
Total02640066

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

View in ClinVar →

Protein Context — Lollipop Plot

CALML3 · 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

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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