CSN1S1

Summary

CSN1S1 (casein alpha s1, HGNC:2445) is a protein-coding gene on chromosome 4q13.3, encoding Alpha-S1-casein (P47710). Important role in the capacity of milk to transport calcium phosphate.

Predicted to be involved in several processes, including response to 11-deoxycorticosterone; response to dehydroepiandrosterone; and response to progesterone. Located in extracellular space.

Source: NCBI Gene 1446 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 27 total
• MANE Select transcript: NM_001890

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2445
Approved symbol	CSN1S1
Name	casein alpha s1
Location	4q13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000126545
Ensembl biotype	protein_coding
OMIM	115450
Entrez	1446

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000246891, ENST00000505782, ENST00000507763, ENST00000507772, ENST00000510936, ENST00000633258, ENST00000949200, ENST00000949201

RefSeq mRNA: 2 — MANE Select: NM_001890 NM_001025104, NM_001890

CCDS: CCDS47067, CCDS54769

Canonical transcript exons

ENST00000246891 — 16 exons

Exon	Start	End
ENSE00000865211	69942536	69942577
ENSE00001024535	69940021	69940044
ENSE00001024555	69932544	69932606
ENSE00001024558	69931068	69931117
ENSE00001024559	69934212	69934244
ENSE00001024561	69937800	69937823
ENSE00001024562	69937121	69937144
ENSE00001024564	69939176	69939208
ENSE00001171278	69936566	69936607
ENSE00001171285	69936456	69936479
ENSE00001171292	69935926	69935949
ENSE00001171300	69934690	69934710
ENSE00001705551	69946196	69946574
ENSE00002454219	69942046	69942063
ENSE00002700741	69944850	69945004
ENSE00003788570	69941019	69941060

Expression profiles

Bgee: expression breadth ubiquitous, 124 present calls, max score 89.45.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1124 / max 47.6216, expressed in 13 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
47845	0.1124	13

Top tissues by expression

276 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.45	gold quality
parotid gland	UBERON:0001831	76.26	silver quality
layer of synovial tissue	UBERON:0007616	74.45	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	71.67	gold quality
synovial joint	UBERON:0002217	68.96	gold quality
adipose tissue	UBERON:0001013	68.45	gold quality
subcutaneous adipose tissue	UBERON:0002190	67.07	gold quality
connective tissue	UBERON:0002384	66.83	gold quality
skin of hip	UBERON:0001554	66.39	silver quality
thoracic mammary gland	UBERON:0005200	61.63	gold quality
mammary gland	UBERON:0001911	61.56	gold quality
cingulate cortex	UBERON:0003027	60.86	gold quality
anterior cingulate cortex	UBERON:0009835	60.53	gold quality
diaphragm	UBERON:0001103	58.41	gold quality
adipose tissue of abdominal region	UBERON:0007808	58.23	gold quality
epithelium of mammary gland	UBERON:0003244	57.91	silver quality
mammary duct	UBERON:0001765	57.61	silver quality
omental fat pad	UBERON:0010414	56.89	gold quality
peritoneum	UBERON:0002358	56.84	gold quality
amniotic fluid	UBERON:0000173	56.59	silver quality
endometrium epithelium	UBERON:0004811	53.13	gold quality
pancreatic ductal cell	CL:0002079	53.05	silver quality
mucosa of transverse colon	UBERON:0004991	52.06	gold quality
lower lobe of lung	UBERON:0008949	51.94	silver quality
vermiform appendix	UBERON:0001154	51.28	gold quality
mucosa of urinary bladder	UBERON:0001259	51.28	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
quadriceps femoris	UBERON:0001377	50.30	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-10885	yes	54899.83
E-MTAB-10855	yes	52657.44
E-MTAB-9841	yes	47918.63
E-ANND-3	yes	4.39

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPG, DNMT1, FOXC1, JUN, STAT5A, STAT5B

miRNA regulators (miRDB)

28 targeting CSN1S1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-26A-1-3P	99.64	66.81	788
HSA-MIR-26A-2-3P	99.64	66.82	786
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-888-5P	99.30	70.15	1855
HSA-MIR-4426	99.17	66.74	1949
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-3146	98.85	66.77	601
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-4290	98.51	65.17	907
HSA-MIR-4720-3P	98.50	68.88	988
HSA-MIR-4662B	98.33	66.37	1163
HSA-MIR-4647	98.30	66.41	1139
HSA-MIR-5579-3P	97.00	68.81	1111
HSA-MIR-3059-3P	96.71	67.08	606
HSA-MIR-3935	96.33	66.79	797
HSA-MIR-2276-5P	96.27	65.85	937
HSA-MIR-7848-3P	95.69	65.00	363

Literature-anchored findings (GeneRIF, showing 4)

• alphas1-Casein may be a potential biomarker for early identification of BPH patients. (PMID:16683014)
• Casein alpha s1 is expressed in human monocytes and stimulates expression of proinflammatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) via an immunomodulatory role beyond the nutritional function of CSN1S1 in milk. (PMID:21135174)
• Results suggest that autoimmunity to insulin can occur infrequently via cross-reactivity to food protein alpha casein. (PMID:21361910)
• Serine-71 in alpha-S1 casein is phosphorylated in the breast milk. (PMID:28786558)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	Csn1s1	ENSMUSG00000070702

Protein

Protein identifiers

Alpha-S1-casein — P47710 (reviewed: P47710)

All UniProt accessions (5): P47710, A0A0J9YVR3, D6RF34, E9PDQ1, H0Y8K1

UniProt curated annotations — full annotation on UniProt →

Function. Important role in the capacity of milk to transport calcium phosphate. Casoxin D acts as opioid antagonist and has vasorelaxing activity mediated by bradykinin B1 receptors.

Subunit / interactions. Heteromultimers of alpha-s1 casein and kappa-casein; disulfide-linked.

Subcellular location. Secreted.

Tissue specificity. Mammary gland specific. Secreted in milk.

Post-translational modifications. Not glycosylated.

Miscellaneous. In milk, the alpha s1- and beta-caseins precipitate in presence of calcium (so-called calcium-sensitive caseins). Kappa-casein prevents the precipitation of the other caseins by calcium through the formation of large stable colloidal particles termed micelles.

Similarity. Belongs to the alpha-casein family.

Isoforms (4)

UniProt ID	Names	Canonical?
P47710-1	1	yes
P47710-2	2
P47710-3	3
P47710-4	4

RefSeq proteins (2): NP_001020275, NP_001881* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026999	Alpha-s1_casein	Family
IPR031305	Casein_CS	Conserved_site

UniProt features (18 total): modified residue 10, splice variant 3, signal peptide 1, chain 1, sequence variant 1, sequence conflict 1, peptide 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P47710-F1	62.57	0.05

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (10): 89, 90, 91, 31, 33, 41, 71, 85, 86, 88

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-5223345	Miscellaneous transport and binding events
R-HSA-382551	Transport of small molecules

MSigDB gene sets: 47 (showing top): GOBP_RESPONSE_TO_ESTRADIOL, GOBP_RESPONSE_TO_CORTICOSTEROID, chr4q13, GOBP_RESPONSE_TO_KETONE, MCBRYAN_PUBERTAL_BREAST_3_4WK_UP, MODULE_99, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, OCT1_07, MCBRYAN_PUBERTAL_BREAST_5_6WK_UP, TGANTCA_AP1_C, GOBP_RESPONSE_TO_STEROID_HORMONE, GOBP_RESPONSE_TO_HORMONE, GOBP_RESPONSE_TO_LIPID, GOBP_RESPONSE_TO_PROGESTERONE, GOBP_RESPONSE_TO_MINERALOCORTICOID

GO Biological Process (4): response to estradiol (GO:0032355), response to progesterone (GO:0032570), response to dehydroepiandrosterone (GO:1903494), response to 11-deoxycorticosterone (GO:1903496)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to ketone	3
response to lipid	2
response to alcohol	2
response to oxygen-containing compound	1
response to steroid hormone	1
response to mineralocorticoid	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

652 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CSN1S1	CSN2	P05814	999
CSN1S1	CSN3	P07498	998
CSN1S1	LALBA	P00709	950
CSN1S1	LTF	P02788	664
CSN1S1	PRL	P01236	652
CSN1S1	ALB	P02768	648
CSN1S1	STAT5A	P42229	572
CSN1S1	BTN1A1	Q13410	544
CSN1S1	DGAT1	O75907	520
CSN1S1	STAT5B	P51692	518
CSN1S1	STATH	P02808	514
CSN1S1	PIGR	P01833	510
CSN1S1	TF	P02787	498
CSN1S1	PAEP	P09466	497
CSN1S1	EFS	O43281	488

IntAct

11 interactions, top by confidence:

A	B	Type	Score
CSN1S1	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
KIF1C	KIF1B	psi-mi:“MI:2364”(proximity)	0.480
CSN1S1	KLK6	psi-mi:“MI:0570”(protein cleavage)	0.440
CUL4A	DDX39A	psi-mi:“MI:0914”(association)	0.350
CSN1S1	TIMP3	psi-mi:“MI:0914”(association)	0.350
CSN1S1	KLHL15	psi-mi:“MI:0914”(association)	0.350
ZFP36L1	CNOT1	psi-mi:“MI:2364”(proximity)	0.270
CSN1S1	UBQLN2	psi-mi:“MI:0915”(physical association)	0.000
TOLLIP	CSN1S1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (43): PDE10A (Affinity Capture-MS), B4GALNT4 (Affinity Capture-MS), LTBP1 (Affinity Capture-MS), EMILIN3 (Affinity Capture-MS), KLHL15 (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), TIMP3 (Affinity Capture-MS), ERF (Affinity Capture-MS), BCOR (Affinity Capture-MS), CDKN2AIP (Affinity Capture-MS), FAM120A (Affinity Capture-MS), ETV3 (Affinity Capture-MS), CSN1S1 (Affinity Capture-MS), CSN1S1 (Affinity Capture-MS), CSN1S1 (Affinity Capture-MS)

ESM2 similar proteins: A1E959, A1E960, A1YQ91, A1YQ92, A1YQ93, A1YQ94, B3A0S0, B4H957, B5DRT7, O55189, O62823, P02662, P02665, P02668, P02669, P02670, P04653, P04656, P06796, P11840, P11841, P18626, P19228, P33618, P39035, P39037, P42155, P42156, P42157, P47710, P50420, P50421, P50422, P50423, P50424, P50425, P79139, P82187, P86273, Q003G9

Diamond homologs: O62823, O97943, P02662, P04653, P04656, P09115, P18626, P39035, P47710, P86272, P19228, P02661

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CSN1S1	up-regulates	RELA	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

27 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	23
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2020 predictions. Top by Δscore:

Variant	Effect	Δscore
4:69942575:GTG:G	donor_gain	1.0000
4:69944848:A:AG	acceptor_gain	1.0000
4:69944848:AGC:A	acceptor_loss	1.0000
4:69944849:G:GT	acceptor_gain	1.0000
4:69944849:GC:G	acceptor_gain	1.0000
4:69944849:GCC:G	acceptor_gain	1.0000
4:69944849:GCCT:G	acceptor_gain	1.0000
4:69944849:GCCTT:G	acceptor_gain	1.0000
4:69945002:GTG:G	donor_gain	1.0000
4:69932602:GGCCT:G	donor_gain	0.9900
4:69932603:GCCTG:G	donor_gain	0.9900
4:69932612:T:G	donor_gain	0.9900
4:69934819:A:G	acceptor_gain	0.9900
4:69935108:T:G	acceptor_gain	0.9900
4:69936478:GG:G	donor_gain	0.9900
4:69936479:GG:G	donor_gain	0.9900
4:69937798:A:G	acceptor_gain	0.9900
4:69939174:A:AG	acceptor_gain	0.9900
4:69939175:G:GG	acceptor_gain	0.9900
4:69939175:GAA:G	acceptor_gain	0.9900
4:69942531:TGCA:T	acceptor_loss	0.9900
4:69942532:GCA:G	acceptor_loss	0.9900
4:69942533:CA:C	acceptor_loss	0.9900
4:69942534:A:AT	acceptor_loss	0.9900
4:69942535:G:GA	acceptor_loss	0.9900
4:69942570:TCC:T	donor_gain	0.9900
4:69944832:AAAT:A	acceptor_gain	0.9900
4:69945000:TGGTG:T	donor_gain	0.9900
4:69945001:GGTG:G	donor_gain	0.9900
4:69945001:GGTGG:G	donor_gain	0.9900

AlphaMissense

1238 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:69932577:T:C	C8R	0.985
4:69944895:T:A	W150R	0.958
4:69944895:T:C	W150R	0.958
4:69932587:C:A	A11D	0.957
4:69932593:C:A	A13D	0.946
4:69944897:G:C	W150C	0.934
4:69944897:G:T	W150C	0.934
4:69932599:C:A	A15D	0.931
4:69932590:T:A	V12D	0.918
4:69945000:T:A	W185R	0.908
4:69945000:T:C	W185R	0.908
4:69932581:T:A	L9H	0.907
4:69932584:T:A	V10E	0.902
4:69932596:T:C	L14P	0.895
4:69932581:T:C	L9P	0.894
4:69932586:G:C	A11P	0.875
4:69932569:T:A	I5N	0.872
4:69932579:T:G	C8W	0.864
4:69932569:T:C	I5T	0.858
4:69932581:T:G	L9R	0.857
4:69932592:G:C	A13P	0.847
4:69932596:T:A	L14H	0.846
4:69944937:T:C	F164L	0.842
4:69944939:T:A	F164L	0.842
4:69944939:T:G	F164L	0.842
4:69932598:G:C	A15P	0.835
4:69932578:G:A	C8Y	0.832
4:69944928:T:C	F161L	0.830
4:69944930:C:A	F161L	0.830
4:69944930:C:G	F161L	0.830

dbSNP variants (sampled 300 via entrez): RS1000188149 (4:69931453 A>G), RS1000240586 (4:69931181 G>C,T), RS10002549 (4:69945254 G>A), RS1000382011 (4:69937313 A>C), RS1000525768 (4:69930186 A>G), RS1000582937 (4:69929907 C>A), RS1000692304 (4:69935698 A>G), RS1000753182 (4:69936933 T>C), RS1000831959 (4:69941862 G>A), RS10009308 (4:69930020 C>T), RS10011226 (4:69935723 C>A,T), RS1001322307 (4:69931047 C>T), RS1001371204 (4:69930758 T>C), RS1001681043 (4:69943134 G>A), RS1001862993 (4:69935418 C>T)

Disease associations

OMIM: gene MIM:115450 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	increases expression	1
zomepirac glucuronide	affects binding	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
2-palmitoylglycerol	increases expression	1
bisphenol S	decreases methylation, affects cotreatment	1
Fulvestrant	affects cotreatment, decreases methylation	1
Azacitidine	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Lipopolysaccharides	affects cotreatment, increases expression	1
Nickel	increases expression	1
Aflatoxin B1	decreases methylation	1
Sodium Selenite	decreases expression	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.