LALBA

Summary

LALBA (lactalbumin alpha, HGNC:6480) is a protein-coding gene on chromosome 12q13.11, encoding Alpha-lactalbumin (P00709). Regulatory subunit of lactose synthase, changes the substrate specificity of galactosyltransferase in the mammary gland making glucose a good acceptor substrate for this enzyme.

This gene encodes alpha-lactalbumin, a principal protein of milk. Alpha-lactalbumin forms the regulatory subunit of the lactose synthase (LS) heterodimer and beta 1,4-galactosyltransferase (beta4Gal-T1) forms the catalytic component. Together, these proteins enable LS to produce lactose by transfering galactose moieties to glucose. As a monomer, alpha-lactalbumin strongly binds calcium and zinc ions and may possess bactericidal or antitumor activity. A folding variant of alpha-lactalbumin, called HAMLET, likely induces apoptosis in tumor and immature cells.

Source: NCBI Gene 3906 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 9 total
• MANE Select transcript: NM_002289

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6480
Approved symbol	LALBA
Name	lactalbumin alpha
Location	12q13.11
Locus type	gene with protein product
Status	Approved
Aliases	LYZL7, LYZG, HAMLET
Ensembl gene	ENSG00000167531
Ensembl biotype	protein_coding
OMIM	149750
Entrez	3906

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000301046, ENST00000549817

RefSeq mRNA: 2 — MANE Select: NM_002289 NM_001384350, NM_002289

CCDS: CCDS8765

Canonical transcript exons

ENST00000301046 — 4 exons

Exon	Start	End
ENSE00001113957	48569888	48570046
ENSE00001113958	48567684	48568017
ENSE00001113959	48568517	48568592
ENSE00001113961	48569082	48569240

Expression profiles

Bgee: expression breadth broad, 75 present calls, max score 88.77.

Top tissues by expression

272 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	88.77	gold quality
sperm	CL:0000019	70.99	gold quality
orbitofrontal cortex	UBERON:0004167	70.67	gold quality
male germ cell	CL:0000015	70.60	gold quality
cervix squamous epithelium	UBERON:0006922	68.60	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	66.46	gold quality
epithelial cell of pancreas	CL:0000083	63.94	gold quality
olfactory bulb	UBERON:0002264	63.87	gold quality
type B pancreatic cell	CL:0000169	63.60	gold quality
triceps brachii	UBERON:0001509	63.13	gold quality
gluteal muscle	UBERON:0002000	63.07	gold quality
endothelial cell	CL:0000115	61.24	gold quality
oocyte	CL:0000023	59.58	gold quality
tongue squamous epithelium	UBERON:0006919	59.23	gold quality
epithelium of mammary gland	UBERON:0003244	59.00	silver quality
mammary duct	UBERON:0001765	58.21	silver quality
left testis	UBERON:0004533	56.77	gold quality
diaphragm	UBERON:0001103	56.21	gold quality
testis	UBERON:0000473	56.15	gold quality
epithelium of nasopharynx	UBERON:0001951	55.86	gold quality
right testis	UBERON:0004534	55.82	gold quality
cervix epithelium	UBERON:0004801	55.13	gold quality
amniotic fluid	UBERON:0000173	54.91	gold quality
tibia	UBERON:0000979	54.05	gold quality
Brodmann (1909) area 46	UBERON:0006483	53.09	gold quality
nasal cavity epithelium	UBERON:0005384	53.08	gold quality
quadriceps femoris	UBERON:0001377	52.91	gold quality
pancreatic ductal cell	CL:0002079	52.14	silver quality
thymus	UBERON:0002370	51.99	gold quality
vastus lateralis	UBERON:0001379	51.91	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-10855	yes	492996.41
E-MTAB-9841	yes	451720.57
E-MTAB-10885	yes	149308.57
E-ANND-3	no	2.14

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): F11, MAF

miRNA regulators (miRDB)

21 targeting LALBA, 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-4524A-3P	99.72	66.85	2406
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-6073	99.60	70.36	793
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-520E-5P	99.27	68.90	1513
HSA-MIR-7854-3P	99.08	66.26	1117
HSA-MIR-6737-3P	98.95	68.56	1577
HSA-MIR-7157-3P	98.95	68.70	1582
HSA-MIR-4272	98.76	68.74	1810
HSA-MIR-5008-3P	98.73	67.50	1433
HSA-MIR-9500	98.62	66.54	1845
HSA-MIR-4665-5P	97.91	67.69	1536
HSA-MIR-4433A-3P	97.75	62.82	1435
HSA-MIR-4308	97.56	67.13	1385
HSA-MIR-6759-3P	96.94	68.31	823
HSA-MIR-3649	96.85	64.10	340
HSA-MIR-6865-5P	96.05	65.58	675
HSA-MIR-6815-5P	96.05	65.55	662
HSA-MIR-659-5P	95.36	65.00	300

Literature-anchored findings (GeneRIF, showing 22)

• hydrogen exchange behavior of variants using mass spectrometry (PMID:11518539)
• comparison of the structural and stability properties of the isolated alpha-helical domain of lysozyme with that of alpha-lactalbumin (PMID:11718563)
• pH-dependent stability of the alpha-lactalbumin molten globule state. (PMID:12833543)
• Structural characterisation of the human alpha-lactalbumin molten globule at high temperature (PMID:12860137)
• a functional Ca(2+)-binding site is not required for conversion of alpha-lactalbumin to the active complex or to cause cell death (PMID:14627739)
• lipids are tissue-specific cofactors in alpha-lactalbumin protein folding (PMID:14627740)
• NMR study of the conformation of HAMLET, the folding variant of human alpha-lactalbumin, complexed to oleic acid. (PMID:15075403)
• The electrostatic nature of the alpha-lactalbumin (LA)-histone interaction justifies use of alpha-LA as a basis for design of antitumor agents, acting through disorganization of chromatin structure due to interaction between alpha-LA and histone. (PMID:15134431)
• a folding variant of alpha-lactalbumin has a role in lactating mammary gland apoptosis (PMID:15141307)
• the non-cooperative denaturation of the molten globule, alpha-lactalbumin secondary structure elements are stabilized by non-specific, non-native interactions (PMID:15558602)
• Fold and topology of alpha-lactalbumin may be formed from degenerate groups of side chains. (PMID:15956205)
• Local interactions as well as hydrophobic interactions formed in the molten globule state play an important role in organizing the structure in the transition state and in guiding the subsequent folding of alpha-lactalbumin. (PMID:16121399)
• Results describe the reaction mechanism and formation of CIDNP (chemically induced dynamic nuclear polarization) in the photoreactions of the dye 2,2’-dipyridyl with non-native states of bovine and human alpha-lactalbumins in aqueous solution. (PMID:16851644)
• alpha-lactalbumin molten globule has even more native-like character than suggested by studies conducted at higher temperature (PMID:18939797)
• recombinant human alpha-LA was purified from transgenic milk and displayed physicochemical properties similar to its natural counterpart with respect to molecular weight, structure, and regulatory activity for beta-1,4-galactosyltransferase (PMID:19038921)
• the structural preferences of the alpha-LA molten globule at pH 7 at the level of individual residues were investigated. (PMID:19766656)
• The complexes formed by partially folded alpha-lactalbumin with oleic acid display selective apoptotic activity against tumor cells. (PMID:19968717)
• Data show that alpha-lactalbumin and CD14 form a complex in the gut which alters degradation of CD14, suggesting a mechanism by which this key LPS receptor may remain functional in the neonatal gut. (PMID:20717070)
• analysis of macromolecular crowding on the structural stability of human alpha-lactalbumin (PMID:22735492)
• High molecular mass complexes are formed with alpha-lactalbumin and alphaB-crystallin, preventing the amorphous aggregation of alpha-lactalbumin. (PMID:23005341)
• Studies indicate that alpha-lactalbumin has two domains, a large alpha-helical domain and a small beta-sheet domain connected by a calcium binding loop. (PMID:27238572)
• human alpha-lactalbumin and human lactoferrin complexes appeared to interact with the chromatin of isolated nuclei affecting chromatin structural organization (PMID:31582209)

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lalba	ENSMUSG00000022991
rattus_norvegicus	Lalba	ENSRNOG00000010811
drosophila_melanogaster	LysB	FBGN0004425
drosophila_melanogaster	LysD	FBGN0004427
drosophila_melanogaster	LysE	FBGN0004428
drosophila_melanogaster	LysP	FBGN0004429
drosophila_melanogaster	LysS	FBGN0004430
drosophila_melanogaster	LysX	FBGN0004431
drosophila_melanogaster	CG16756	FBGN0029765
drosophila_melanogaster	CG7798	FBGN0034092
drosophila_melanogaster	CG16799	FBGN0034538
drosophila_melanogaster	CG11159	FBGN0034539
drosophila_melanogaster	CG8492	FBGN0035813
drosophila_melanogaster	CG30062	FBGN0050062

Paralogs (8): LYZ (ENSG00000090382), LYZL1 (ENSG00000120563), SPACA3 (ENSG00000141316), LYZL2 (ENSG00000151033), LYZL4 (ENSG00000157093), SPACA5B (ENSG00000171478), SPACA5 (ENSG00000171489), LYZL6 (ENSG00000275722)

Protein

Protein identifiers

Alpha-lactalbumin — P00709 (reviewed: P00709)

Alternative names: Lactose synthase B protein, Lysozyme-like protein 7

All UniProt accessions (3): A0A080YV01, P00709, F8VWU1

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory subunit of lactose synthase, changes the substrate specificity of galactosyltransferase in the mammary gland making glucose a good acceptor substrate for this enzyme. This enables LS to synthesize lactose, the major carbohydrate component of milk. In other tissues, galactosyltransferase transfers galactose onto the N-acetylglucosamine of the oligosaccharide chains in glycoproteins.

Subunit / interactions. Lactose synthase (LS) is a heterodimer of a catalytic component, beta1,4-galactosyltransferase (beta4Gal-T1) and a regulatory component, alpha-lactalbumin (LA).

Subcellular location. Secreted.

Tissue specificity. Mammary gland specific. Secreted in milk.

Similarity. Belongs to the glycosyl hydrolase 22 family.

RefSeq proteins (2): NP_001371279, NP_002280* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000545	Lactalbumin	Family
IPR001916	Glyco_hydro_22	Family
IPR019799	Glyco_hydro_22_CS	Domain
IPR023346	Lysozyme-like_dom_sf	Homologous_superfamily

Pfam: PF00062

UniProt features (39 total): binding site 11, helix 9, strand 5, disulfide bond 4, turn 3, glycosylation site 2, signal peptide 1, chain 1, domain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
1B9O	X-RAY DIFFRACTION	1.15
3B0O	X-RAY DIFFRACTION	1.61
1HML	X-RAY DIFFRACTION	1.7
1A4V	X-RAY DIFFRACTION	1.8
3B0I	X-RAY DIFFRACTION	1.8
4L41	X-RAY DIFFRACTION	2.7
1CB3	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P00709-F1	91.50	0.83

Functional residue map

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

Ligand- & substrate-binding residues (11): 103; 106; 107; 135; 57; 58; 68; 98; 100; 101; 102

Disulfide bonds (4): 25–139, 47–130, 80–96, 92–110

Glycosylation sites (2): 64, 90

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-5653890	Lactose synthesis
R-HSA-9927426	Developmental Lineage of Mammary Gland Alveolar Cells
R-HSA-1430728	Metabolism
R-HSA-71387	Metabolism of carbohydrates and carbohydrate derivatives

MSigDB gene sets: 86 (showing top): GOBP_OLIGOSACCHARIDE_METABOLIC_PROCESS, MODULE_92, GOBP_CELL_CELL_SIGNALING, MCBRYAN_PUBERTAL_BREAST_3_4WK_UP, MODULE_99, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_DEFENSE_RESPONSE_TO_GRAM_NEGATIVE_BACTERIUM, GOBP_DEFENSE_RESPONSE_TO_GRAM_POSITIVE_BACTERIUM, BROWN_MYELOID_CELL_DEVELOPMENT_UP, GOBP_OLIGOSACCHARIDE_BIOSYNTHETIC_PROCESS, MAF_Q6, GOBP_DEFENSE_RESPONSE_TO_BACTERIUM, REACTOME_METABOLISM_OF_CARBOHYDRATES_AND_CARBOHYDRATE_DERIVATIVES, YAGI_AML_WITH_11Q23_REARRANGED, GOCC_GOLGI_LUMEN

GO Biological Process (7): lactose biosynthetic process (GO:0005989), apoptotic process (GO:0006915), signal transduction (GO:0007165), cell-cell signaling (GO:0007267), defense response to bacterium (GO:0042742), defense response to Gram-negative bacterium (GO:0050829), defense response to Gram-positive bacterium (GO:0050830)

GO Molecular Function (5): lysozyme activity (GO:0003796), lactose synthase activity (GO:0004461), calcium ion binding (GO:0005509), enzyme-substrate adaptor activity (GO:0140767), metal ion binding (GO:0046872)

GO Cellular Component (5): Golgi membrane (GO:0000139), obsolete extracellular space (GO:0005615), Golgi lumen (GO:0005796), protein-containing complex (GO:0032991), extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Metabolism of carbohydrates and carbohydrate derivatives	1
Developmental Lineages of the Mammary Gland	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell communication	2
signaling	2
defense response to bacterium	2
Golgi apparatus	2
lactose metabolic process	1
disaccharide biosynthetic process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cellular process	1
regulation of cellular process	1
cellular response to stimulus	1
defense response	1
response to bacterium	1
hydrolase activity, hydrolyzing O-glycosyl compounds	1
peptidoglycan muralytic activity	1
UDP-galactosyltransferase activity	1
metal ion binding	1
protein-macromolecule adaptor activity	1
cation binding	1
bounding membrane of organelle	1
intracellular organelle lumen	1
cellular_component	1
cellular anatomical structure	1

Protein interactions and networks

STRING

817 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LALBA	LTF	P02788	999
LALBA	ALB	P02768	997
LALBA	CSN3	P07498	981
LALBA	B4GALT1	P15291	979
LALBA	CSN2	P05814	970
LALBA	LPO	P22079	952
LALBA	CSN1S1	P47710	950
LALBA	MB	P02144	918
LALBA	HSPD1	P10809	852
LALBA	INS	P01308	727
LALBA	CYCS	P00001	713
LALBA	RNASE1	P07998	709
LALBA	HSPA8	P11142	682
LALBA	PRL	P01236	633
LALBA	B4GALNT2	Q8NHY0	610

IntAct

2 interactions, top by confidence:

A	B	Type	Score
PIPOX	LALBA	psi-mi:“MI:0914”(association)	0.350

BioGRID (7): LALBA (Biochemical Activity), HIST2H3A (Reconstituted Complex), LALBA (Reconstituted Complex), LALBA (Affinity Capture-MS), LALBA (Reconstituted Complex), HSPA8 (Reconstituted Complex), LALBA (Reconstituted Complex)

ESM2 similar proteins: A2AE20, C0HLB7, C1IIX1, D4ABW7, D9J142, D9J143, G3XDT7, O75951, P00702, P00709, P00710, P00711, P00712, P00713, P00714, P00716, P05105, P07458, P08334, P08896, P09462, P11375, P11376, P12065, P18137, P28546, P29752, P30805, P37161, P48816, P50717, P50718, P51782, P61944, P81646, P81708, P85045, Q06655, Q29145, Q29RT1

Diamond homologs: A0JNM6, B6VH76, P00697, P00698, P00699, P00700, P00701, P00705, P00708, P00709, P00710, P00711, P00712, P00713, P00714, P00716, P04421, P07458, P08334, P08896, P08905, P09462, P11375, P11376, P11941, P12065, P12066, P12067, P12068, P12069, P16973, P17607, P17897, P18137, P24364, P24533, P28546, P29752, P30201, P30805

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
LALBA	“form complex”	“Lactose synthase complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	9
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

525 predictions. Top by Δscore:

Variant	Effect	Δscore
12:48568603:T:C	acceptor_gain	1.0000
12:48569080:A:AC	donor_gain	1.0000
12:48569081:C:CG	donor_gain	1.0000
12:48569238:TCA:T	acceptor_gain	1.0000
12:48569239:CA:C	acceptor_gain	1.0000
12:48569239:CAC:C	acceptor_gain	1.0000
12:48569241:C:CC	acceptor_gain	1.0000
12:48569881:AACT:A	donor_loss	1.0000
12:48569882:ACT:A	donor_loss	1.0000
12:48569883:CTC:C	donor_loss	1.0000
12:48569884:TCA:T	donor_loss	1.0000
12:48569885:CACA:C	donor_loss	1.0000
12:48569886:A:AC	donor_gain	1.0000
12:48569886:ACATT:A	donor_gain	1.0000
12:48569887:C:CC	donor_gain	1.0000
12:48569887:CA:C	donor_gain	1.0000
12:48569887:CATT:C	donor_gain	1.0000
12:48569887:CATTC:C	donor_gain	1.0000
12:48568528:T:A	donor_gain	0.9900
12:48568591:CT:C	acceptor_gain	0.9900
12:48568603:T:TC	acceptor_gain	0.9900
12:48568606:C:CT	acceptor_gain	0.9900
12:48569073:GCTAC:G	donor_loss	0.9900
12:48569074:CTACT:C	donor_loss	0.9900
12:48569075:TAC:T	donor_loss	0.9900
12:48569076:AC:A	donor_loss	0.9900
12:48569077:C:CA	donor_loss	0.9900
12:48569078:T:TC	donor_loss	0.9900
12:48569079:C:CC	donor_loss	0.9900
12:48569080:AC:A	donor_loss	0.9900

AlphaMissense

953 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:48568017:C:A	W123C	0.937
12:48568017:C:G	W123C	0.937
12:48569135:C:G	C80S	0.935
12:48569136:A:T	C80S	0.935
12:48569099:C:G	C92S	0.918
12:48569100:A:T	C92S	0.918
12:48567997:C:G	C130S	0.917
12:48567998:A:T	C130S	0.917
12:48568556:C:G	C110S	0.917
12:48568557:A:T	C110S	0.917
12:48569224:A:C	F50L	0.905
12:48569224:A:T	F50L	0.905
12:48569226:A:G	F50L	0.905
12:48567975:C:A	W137C	0.898
12:48567975:C:G	W137C	0.898
12:48569139:A:G	W79R	0.893
12:48569139:A:T	W79R	0.893
12:48569137:C:A	W79C	0.891
12:48569137:C:G	W79C	0.891
12:48569234:C:G	C47S	0.886
12:48569235:A:T	C47S	0.886
12:48569215:A:C	S53R	0.885
12:48569215:A:T	S53R	0.885
12:48569217:T:G	S53R	0.885
12:48569165:C:T	G70E	0.879
12:48569233:A:C	C47W	0.871
12:48567996:G:C	C130W	0.869
12:48568557:A:G	C110R	0.869
12:48569235:A:G	C47R	0.869
12:48569087:C:G	C96S	0.867

dbSNP variants (sampled 300 via entrez): RS1000205309 (12:48571621 G>A), RS1000724046 (12:48571851 G>A), RS1001001577 (12:48567614 A>G,T), RS1001324354 (12:48573032 G>C,T), RS1001608635 (12:48572823 A>G), RS1002730383 (12:48569665 A>G), RS1004174557 (12:48572703 T>C,G), RS1004228825 (12:48572393 G>T), RS1004285887 (12:48573710 T>G), RS1004361298 (12:48571044 CT>C), RS1004413731 (12:48571312 T>C), RS1005116786 (12:48570211 C>A,T), RS1005288582 (12:48568035 G>A), RS1006174031 (12:48571014 T>C), RS1006530993 (12:48571242 G>A,C)

Disease associations

OMIM: gene MIM:149750 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002233_2	Adiponectin levels	1.000000e-07
GCST004862_199	Itch intensity from mosquito bite adjusted by bite size	6.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004502	adiponectin measurement
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
propionaldehyde	increases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	decreases expression	1
Amphotericin B	increases expression	1
Benzo(a)pyrene	increases methylation	1

Clinical trials (associated diseases)

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