CSN1S1

Chr 4

casein alpha s1

Also known as: CASA, CSN1

The protein is a major milk protein with an important role in the capacity of milk to transport calcium phosphate. Mutations cause autosomal recessive congenital lactase deficiency, which presents in infancy with severe diarrhea, dehydration, and failure to thrive when exposed to lactose-containing milk. The gene shows very low constraint to loss-of-function variants, consistent with its specialized role in milk composition rather than essential cellular functions.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.71
Clinical SummaryCSN1S1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.71LOEUF
pLI 0.000
Z-score -0.85
OE 1.22 (0.871.71)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.32Z-score
OE missense 0.90 (0.751.09)
80 obs / 88.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.22 (0.871.71)
00.351.4
Missense OE0.90 (0.751.09)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 22 / 18.1Missense obs/exp: 80 / 88.5Syn Z: 0.14
DN
0.79top 25%
GOF
0.5954th %ile
LOF
0.1598th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CSN1S1 · 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.

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Clinical Literature
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