CSN1S1

Chr 4

casein alpha s1

Also known as: CASA, CSN1

NCBI Gene: 1446 ENSG00000126545 UniProt: P47710 OMIM: 115450

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.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to be involved in several processes, including response to 11-deoxycorticosterone; response to dehydroepiandrosterone; and response to progesterone. Located in obsolete extracellular space. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.71

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.71LOEUF

pLI 0.000

Z-score -0.85

OE 1.22 (0.87–1.71)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.32Z-score

OE missense 0.90 (0.75–1.09)

80 obs / 88.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.22 (0.87–1.71)

0≤0.351.4

Missense OE?0.90 (0.75–1.09)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 22 / 18.1Missense obs/exp: 80 / 88.5Syn Z: 0.14

Background carrier burden — how many people carry a rare variant somewhere in CSN1S1?

gnomAD v4 · ~730k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 140

278 rare PASS variants

Rare truncating (LoF)

1 in 790

92 rare PASS variants

Rare synonymous (reference)

1 in 500

81 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CSN1S1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 200	1 in 730
South Asian	~43k	1 in 190	1 in 750
Remaining (unassigned)	~30k	1 in 140	1 in 970
European (Finnish)	~27k	1 in 1,100	1 in 3,700
Admixed American	~22k	1 in 210	1 in 1,100
African / African American	~21k	1 in 230	1 in 2,200
East Asian	~20k	1 in 130	1 in 490
Ashkenazi Jewish	~13k	1 in 2,600	1 in 710
Middle Eastern	~2,882	1 in 160	1 in 350

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 6 of 15 coding exons well covered in gnomAD exomes; exons 11, 16 poorly covered; exons 5, 6, 8, 9, 10 and 2 more marginal. Genomes: all 15.? see exons ↓