SCGB2A1

Summary

SCGB2A1 (secretoglobin family 2A member 1, HGNC:7051) is a protein-coding gene on chromosome 11q12.3, encoding Mammaglobin-B (O75556). May bind androgens and other steroids, may also bind estramustine, a chemotherapeutic agent used for prostate cancer.

Involved in androgen receptor signaling pathway. Located in extracellular space.

Source: NCBI Gene 4246 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 22 total
• MANE Select transcript: NM_002407

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7051
Approved symbol	SCGB2A1
Name	secretoglobin family 2A member 1
Location	11q12.3
Locus type	gene with protein product
Status	Approved
Aliases	UGB3, LPHC, MGC71973
Ensembl gene	ENSG00000124939
Ensembl biotype	protein_coding
OMIM	604398
Entrez	4246

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000244930

RefSeq mRNA: 1 — MANE Select: NM_002407 NM_002407

CCDS: CCDS8016

Canonical transcript exons

ENST00000244930 — 3 exons

Exon	Start	End
ENSE00000990910	62208673	62208786
ENSE00000990911	62210413	62210600
ENSE00001327099	62213726	62213943

Expression profiles

Bgee: expression breadth ubiquitous, 150 present calls, max score 99.75.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.0233 / max 366.8990, expressed in 80 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
114674	0.9488	77
114676	0.0556	15
114675	0.0189	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	99.75	gold quality
right uterine tube	UBERON:0001302	99.61	gold quality
caput epididymis	UBERON:0004358	99.38	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.99	gold quality
type B pancreatic cell	CL:0000169	98.41	gold quality
bronchial epithelial cell	CL:0002328	96.52	gold quality
endometrium	UBERON:0001295	95.96	gold quality
islet of Langerhans	UBERON:0000006	95.91	gold quality
epithelium of bronchus	UBERON:0002031	95.84	gold quality
nasal cavity epithelium	UBERON:0005384	95.39	gold quality
bronchus	UBERON:0002185	95.04	gold quality
cauda epididymis	UBERON:0004360	94.98	gold quality
nasal cavity mucosa	UBERON:0001826	93.88	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.78	gold quality
palpebral conjunctiva	UBERON:0001812	89.31	gold quality
mucosa of sigmoid colon	UBERON:0004993	87.46	gold quality
pancreatic ductal cell	CL:0002079	86.47	gold quality
rectum	UBERON:0001052	84.46	gold quality
epithelial cell of pancreas	CL:0000083	84.29	silver quality
fallopian tube	UBERON:0003889	83.95	gold quality
left uterine tube	UBERON:0001303	83.87	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.39	silver quality
colonic mucosa	UBERON:0000317	82.78	gold quality
saliva-secreting gland	UBERON:0001044	81.79	gold quality
gall bladder	UBERON:0002110	81.26	gold quality
minor salivary gland	UBERON:0001830	81.19	gold quality
pancreas	UBERON:0001264	80.87	gold quality
parotid gland	UBERON:0001831	80.07	silver quality
seminal vesicle	UBERON:0000998	79.96	gold quality
epithelium of nasopharynx	UBERON:0001951	79.59	silver quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 13.

Experiment	Marker?	Max mean expression
E-MTAB-10287	yes	9768.54
E-MTAB-10283	yes	8157.50
E-MTAB-6701	yes	3295.57
E-GEOD-124263	yes	1886.44
E-MTAB-10885	yes	1229.28
E-GEOD-83139	yes	316.32
E-GEOD-81547	yes	24.02
E-MTAB-5061	yes	17.49
E-HCAD-31	yes	13.28
E-HCAD-1	yes	9.97
E-GEOD-81608	yes	8.74
E-ENAD-27	yes	4.67
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SP3

miRNA regulators (miRDB)

19 targeting SCGB2A1, 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-3692-3P	99.98	70.27	2139
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-5683	99.36	68.59	2083
HSA-MIR-4687-5P	99.14	66.26	488
HSA-MIR-4801	98.96	69.42	2096
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-1304-5P	98.90	68.58	1054
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-4731-3P	98.56	68.60	1860
HSA-MIR-4709-5P	98.51	67.25	1335
HSA-MIR-1199-5P	98.44	66.51	829
HSA-MIR-6751-3P	98.44	66.35	835
HSA-MIR-6516-5P	98.42	70.19	1551
HSA-MIR-8078	98.32	65.73	361
HSA-MIR-3187-3P	97.38	65.80	904

Literature-anchored findings (GeneRIF, showing 16)

• The mammaglobin/lipophilin B complex is a promising diagnostic marker for breast cancer. (PMID:12022875)
• MGB2 markers may be useful for identifying micrometastases in sentinel lymph nodes of breast cancer patients. (PMID:15151203)
• SCGB 2A1 represents a new class of androgen target genes that are purely under indirect AR control mediated by DNA-bound Sp factors. (PMID:16020486)
• Results indicate that mammaglobin, as measured by the ELISA, holds significant promise for breast cancer screening with the realistic potential to impact management of this disease. (PMID:16166429)
• MGB-2 is highly expressed in endometrioid endometrial cancer [EEC], particularly in well- and moderately differentiated tumors, and may represent a novel molecular marker for EEC (PMID:18021217)
• Expression levels of mammaglobins A and B in nasal polyps are not different between patients with and without AR (PMID:18416968)
• MGB-2 expression characterizes less aggressive forms of EOC and is correlated with a favorable outcome (PMID:19635143)
• Data show that plasma mammaglobin mRNA alone or in combination with CA15.3 (CD227) may be used as a valuable noninvasive approach for the diagnosis and the detection of metastasis in breast cancer at the time of diagnosis. (PMID:20306663)
• MGB has the highest expression in HER2-overexpressing breast cancers and may be a potentially useful marker for this subtype. (PMID:23332923)
• SCGB2A1 is a top differentially expressed gene in all major histological types of ovarian cancers. (PMID:23807163)
• Results indicated that SCGB2A1 represented a novel, prognostic factor for colorectal cancer, and its expression correlated with chemoresistance, radioresistance and cancer cell stemness. (PMID:24585249)
• The data indicate that MGB1, MGB2 and LIPB mRNAs are expressed at low levels in human tissues but basal expression is upregulated in ovarian cancer. (PMID:24603286)
• Results indicate that the quantitative analysis of h-MAM mRNA is a useful tool for detecting CTCs in breast cancer patients. (PMID:24706379)
• The commonly used breast carcinoma biomarkers vary in their prognostic implications. GCDFP-15 independently indicated a favourable prognosis. GATA-3 and MGB were not associated with outcome. (PMID:25425335)
• novel marker GATA3 stains a significantly higher proportion of both primary and metastatic breast carcinomas than GCDFP15 or mammaglobin with stronger and more diffuse staining, helpful in cases with small tissue samples (PMID:25906123)
• The expression of HOXB13, IL17BR, and mammaglobin 1 in sentinel lymph nodes predict the outcome of primary breast cancer patients. (PMID:29729704)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Scgb2a2	ENSMUSG00000096872
rattus_norvegicus	Scgb2a1	ENSRNOG00000020305
rattus_norvegicus	Scgb2a1	ENSRNOG00000023151

Paralogs (1): SCGB2A2 (ENSG00000110484)

Protein

Protein identifiers

Mammaglobin-B — O75556 (reviewed: O75556)

Alternative names: Lacryglobin, Lipophilin-C, Mammaglobin-2, Secretoglobin family 2A member 1

All UniProt accessions (1): O75556

UniProt curated annotations — full annotation on UniProt →

Function. May bind androgens and other steroids, may also bind estramustine, a chemotherapeutic agent used for prostate cancer. May be under transcriptional regulation of steroid hormones.

Subunit / interactions. Heterodimer of a lipophilin A and a lipophilin C (mammaglobin B) monomer associated head to head.

Subcellular location. Secreted.

Tissue specificity. Expressed in thymus, trachea, kidney, steroid responsive tissues (prostate, testis, uterus, breast and ovary) and salivary gland.

Similarity. Belongs to the secretoglobin family. Lipophilin subfamily.

RefSeq proteins (1): NP_002398* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016126	Secretoglobin	Family
IPR035960	Secretoglobin_sf	Homologous_superfamily

Pfam: PF01099

UniProt features (3 total): signal peptide 1, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75556-F1	87.56	0.59

Functional residue map

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

Glycosylation sites (1): 68

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 64 (showing top): GOBP_CELLULAR_RESPONSE_TO_LIPID, SMID_BREAST_CANCER_RELAPSE_IN_LUNG_DN, MODULE_404, GOBP_HORMONE_MEDIATED_SIGNALING_PATHWAY, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, MODULE_99, GOBP_RESPONSE_TO_STEROID_HORMONE, GOBP_RESPONSE_TO_HORMONE, GOBP_RESPONSE_TO_LIPID, GOBP_CELLULAR_RESPONSE_TO_STEROID_HORMONE_STIMULUS, GOBP_INTRACELLULAR_RECEPTOR_SIGNALING_PATHWAY, GOBP_STEROID_HORMONE_RECEPTOR_SIGNALING_PATHWAY, VECCHI_GASTRIC_CANCER_EARLY_DN, GOBP_ANDROGEN_RECEPTOR_SIGNALING_PATHWAY

GO Biological Process (1): androgen receptor signaling pathway (GO:0030521)

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

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear receptor-mediated steroid hormone signaling pathway	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

450 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SCGB2A1	SCGB1D1	O95968	875
SCGB2A1	SCGB1A1	P11684	733
SCGB2A1	SCGB1D2	O95969	695
SCGB2A1	SCGB3A2	Q96PL1	623
SCGB2A1	MUC7	Q8TAX7	592
SCGB2A1	LCN1	P31025	578
SCGB2A1	PRR4	Q16378	577
SCGB2A1	PLA2G7	Q13093	548
SCGB2A1	KCNS3	Q9BQ31	548
SCGB2A1	PTGDR2	Q9Y5Y4	542
SCGB2A1	HNMT	P50135	497
SCGB2A1	ADAM33	Q9BZ11	497
SCGB2A1	PHF11	Q9UIL8	497
SCGB2A1	KCNMB1	P78475	491
SCGB2A1	LACRT	Q9GZZ8	480

IntAct

56 interactions, top by confidence:

A	B	Type	Score
AEBP2	EED	psi-mi:“MI:0914”(association)	0.650
DDX31	IGLL5	psi-mi:“MI:0914”(association)	0.530
HBM	SCGB2A1	psi-mi:“MI:0914”(association)	0.530
DAAM2	SCGB2A1	psi-mi:“MI:0914”(association)	0.530
DNAJB8	SCGB2A1	psi-mi:“MI:0914”(association)	0.530
TSGA13	SCGB2A1	psi-mi:“MI:0914”(association)	0.530
SCGB2A1	SLC27A2	psi-mi:“MI:0914”(association)	0.530
CBX1	ZNF292	psi-mi:“MI:0914”(association)	0.530
CCDC158	SCGB2A1	psi-mi:“MI:0915”(physical association)	0.400
KSR1	DDX39A	psi-mi:“MI:0914”(association)	0.350
SUSD3	IGLL5	psi-mi:“MI:0914”(association)	0.350
SNX27	IGLL5	psi-mi:“MI:0914”(association)	0.350
CCDC148	SCGB2A1	psi-mi:“MI:0914”(association)	0.350
SLC2A6	SCGB2A1	psi-mi:“MI:0914”(association)	0.350
PIK3CA	SCGB2A1	psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350
GOLGA8A	ZNF320	psi-mi:“MI:0914”(association)	0.350
OR13C3	POTEF	psi-mi:“MI:0914”(association)	0.350
SCGB2A1	RAP1BL	psi-mi:“MI:0914”(association)	0.350
DHRS12	IGLL5	psi-mi:“MI:0914”(association)	0.350
GJB5	IGLL5	psi-mi:“MI:0914”(association)	0.350
TMEM176B	IGLL5	psi-mi:“MI:0914”(association)	0.350

BioGRID (122): SCGB2A1 (Affinity Capture-MS), SCGB2A1 (Affinity Capture-MS), SCGB2A1 (Affinity Capture-MS), SCGB2A1 (Affinity Capture-MS), SCGB2A1 (Affinity Capture-MS), SCGB2A1 (Affinity Capture-MS), SCGB2A1 (PCA), SCGB2A1 (Affinity Capture-MS), SCGB2A1 (Affinity Capture-MS), SCGB2A1 (Affinity Capture-MS), SCGB2A1 (Affinity Capture-MS), SCGB2A1 (Affinity Capture-MS), SCGB2A1 (Affinity Capture-MS), SCGB2A1 (Affinity Capture-MS), SCGB2A1 (Affinity Capture-MS)

ESM2 similar proteins: A0A8M9PDM1, A0JNP2, O09051, O75556, O95968, O95969, P02779, P02780, P02781, P02782, P04769, P06913, P09320, P0DMR2, P11684, P17559, P28902, P30438, P30440, P33578, P33579, P33580, P33680, P70664, P70668, P79897, Q02747, Q05702, Q06318, Q0PGP2, Q13296, Q16661, Q28358, Q2VPS3, Q4G0G5, Q6UGQ3, Q6XE38, Q7M742, Q7M747, Q8CGZ9

Diamond homologs: O75556, P02780, Q13296, Q9JHB9

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 58 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
heterochromatin formation	5	27.2×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	15
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

260 predictions. Top by Δscore:

Variant	Effect	Δscore
11:62208782:TGCAG:T	donor_gain	1.0000
11:62208783:GCAG:G	donor_gain	1.0000
11:62208783:GCAGG:G	donor_gain	1.0000
11:62208784:CAG:C	donor_gain	1.0000
11:62208785:AGGT:A	donor_loss	1.0000
11:62208787:G:GA	donor_loss	1.0000
11:62208787:G:GG	donor_gain	1.0000
11:62210408:TCCAG:T	acceptor_loss	1.0000
11:62210409:CCAGA:C	acceptor_loss	1.0000
11:62210411:A:AG	acceptor_gain	1.0000
11:62210412:G:A	acceptor_loss	1.0000
11:62210412:G:GA	acceptor_gain	1.0000
11:62210412:GA:G	acceptor_gain	1.0000
11:62210412:GAT:G	acceptor_gain	1.0000
11:62210412:GATT:G	acceptor_gain	1.0000
11:62210412:GATTC:G	acceptor_gain	1.0000
11:62208785:AG:A	donor_gain	0.9900
11:62208786:GG:G	donor_gain	0.9900
11:62210529:GC:G	donor_gain	0.9900
11:62210597:GATG:G	donor_gain	0.9900
11:62210598:ATGGT:A	donor_loss	0.9800
11:62210599:TGG:T	donor_loss	0.9800
11:62210601:G:A	donor_loss	0.9800
11:62210602:T:G	donor_loss	0.9800
11:62213725:GC:G	acceptor_gain	0.9800
11:62210601:G:GG	donor_gain	0.9700
11:62213724:A:AG	acceptor_gain	0.9700
11:62213725:G:GG	acceptor_gain	0.9700
11:62208787:G:T	donor_gain	0.9500
11:62208788:T:A	donor_loss	0.9500

AlphaMissense

644 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:62210546:G:C	K63N	0.926
11:62210546:G:T	K63N	0.926
11:62210553:T:C	F66L	0.864
11:62210555:C:A	F66L	0.864
11:62210555:C:G	F66L	0.864
11:62210502:T:C	F49L	0.845
11:62210504:C:A	F49L	0.845
11:62210504:C:G	F49L	0.845
11:62210545:A:C	K63T	0.739
11:62213741:A:C	S87R	0.728
11:62213743:C:A	S87R	0.728
11:62213743:C:G	S87R	0.728
11:62210586:T:C	F77L	0.727
11:62210588:T:A	F77L	0.727
11:62210588:T:G	F77L	0.727
11:62210545:A:T	K63M	0.681
11:62210482:A:C	Y42S	0.667
11:62210544:A:G	K63E	0.644
11:62210481:T:C	Y42H	0.611
11:62210529:G:C	A58P	0.596
11:62210557:T:C	L67P	0.583

dbSNP variants (sampled 300 via entrez): RS1000488429 (11:62211017 G>A), RS1000505003 (11:62212405 C>T), RS1000700389 (11:62209927 G>A), RS1000776193 (11:62211258 G>A,T), RS1001003847 (11:62212677 A>G), RS1001319650 (11:62210739 C>A,G,T), RS1001913893 (11:62213005 C>T), RS1001923941 (11:62207229 C>T), RS1002938356 (11:62208905 G>A), RS1002943425 (11:62208705 C>T), RS1003075630 (11:62214331 G>T), RS1003106716 (11:62214080 C>T), RS1003262322 (11:62208344 G>A), RS1003269165 (11:62207822 C>A,T), RS1003399913 (11:62209219 CTG>C)

Disease associations

OMIM: gene MIM:604398 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST002446_1	Plasma omega-6 polyunsaturated fatty acid levels (linoleic acid)	4.000000e-274
GCST002446_7	Plasma omega-6 polyunsaturated fatty acid levels (linoleic acid)	3.000000e-21
GCST002449_6	Plasma omega-6 polyunsaturated fatty acid levels (arachidonic acid)	0.000000e+00
GCST002449_8	Plasma omega-6 polyunsaturated fatty acid levels (arachidonic acid)	7.000000e-147
GCST005956_12	Waist-to-hip ratio adjusted for BMI	2.000000e-06
GCST005956_2	Waist-to-hip ratio adjusted for BMI	1.000000e-08
GCST005962_37	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	5.000000e-07
GCST005962_51	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	1.000000e-07

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0005680	omega-6 polyunsaturated fatty acid measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, increases expression, increases methylation	2
Nickel	decreases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Aflatoxin B1	affects expression, increases methylation	2
potassium persulfate	increases expression	1
sodium arsenite	increases expression	1
bicalutamide	decreases reaction, increases expression	1
Zoledronic Acid	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Allergens	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Polychlorinated Biphenyls	affects expression	1
Progesterone	affects cotreatment, increases expression	1
Smoke	increases abundance, increases expression	1
Dihydrotestosterone	increases expression, affects binding, increases reaction, decreases reaction	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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