SCGB2A2

Summary

SCGB2A2 (secretoglobin family 2A member 2, HGNC:7050) is a protein-coding gene on chromosome 11q12.3, encoding Mammaglobin-A (Q13296).

Predicted to be involved in androgen receptor signaling pathway. Predicted to be located in extracellular region. Predicted to be active in extracellular space.

Source: NCBI Gene 4250 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 20 total
• MANE Select transcript: NM_002411

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7050
Approved symbol	SCGB2A2
Name	secretoglobin family 2A member 2
Location	11q12.3
Locus type	gene with protein product
Status	Approved
Aliases	UGB2, MGC71974
Ensembl gene	ENSG00000110484
Ensembl biotype	protein_coding
OMIM	605562
Entrez	4250

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000227918, ENST00000525380

RefSeq mRNA: 1 — MANE Select: NM_002411 NM_002411

CCDS: CCDS8018

Canonical transcript exons

ENST00000227918 — 3 exons

Exon	Start	End
ENSE00000722532	62270881	62271068
ENSE00000851090	62270158	62270271
ENSE00001119155	62272957	62273160

Expression profiles

Bgee: expression breadth ubiquitous, 160 present calls, max score 99.58.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 4.2069 / max 5075.3361, expressed in 30 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
114683	4.2069	30

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper leg skin	UBERON:0004262	99.58	gold quality
upper arm skin	UBERON:0004263	99.12	gold quality
skin of hip	UBERON:0001554	98.92	gold quality
epithelium of mammary gland	UBERON:0003244	97.73	gold quality
mammary duct	UBERON:0001765	97.61	gold quality
skin of leg	UBERON:0001511	96.80	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	95.00	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.65	gold quality
zone of skin	UBERON:0000014	94.27	gold quality
mammary gland	UBERON:0001911	93.32	gold quality
thoracic mammary gland	UBERON:0005200	93.28	gold quality
skin of abdomen	UBERON:0001416	92.83	gold quality
minor salivary gland	UBERON:0001830	81.63	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.53	gold quality
nipple	UBERON:0002030	79.79	gold quality
mouth mucosa	UBERON:0003729	76.72	gold quality
saliva-secreting gland	UBERON:0001044	76.03	gold quality
buccal mucosa cell	CL:0002336	71.86	silver quality
endocervix	UBERON:0000458	70.38	gold quality
nasal cavity mucosa	UBERON:0001826	69.07	gold quality
hair follicle	UBERON:0002073	67.83	gold quality
superior surface of tongue	UBERON:0007371	67.80	gold quality
endometrium	UBERON:0001295	65.43	gold quality
lower esophagus mucosa	UBERON:0035834	60.81	gold quality
pharyngeal mucosa	UBERON:0000355	59.29	gold quality
right lung	UBERON:0002167	58.19	gold quality
gastrocnemius	UBERON:0001388	56.85	gold quality
decidua	UBERON:0002450	56.55	gold quality
right coronary artery	UBERON:0001625	56.49	gold quality
uterus	UBERON:0000995	55.84	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-9841	yes	10666.97
E-MTAB-10855	yes	10490.05
E-MTAB-10885	yes	8937.18
E-HCAD-1	yes	8.09
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1

miRNA regulators (miRDB)

15 targeting SCGB2A2, 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-4776-3P	100.00	68.73	1340
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-511-5P	98.97	70.94	2268
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-10A-5P	98.89	69.85	712
HSA-MIR-10B-5P	98.89	69.86	711
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-4703-3P	96.68	68.61	545
HSA-MIR-431-5P	96.16	66.50	652

Literature-anchored findings (GeneRIF, showing 40)

• Expression of MGB1 transcript is associated with breast cancer (PMID:14696125)
• MGB1 markers may be useful for identifying micrometastases in sentinel lymph nodes of breast cancer patients. (PMID:15151203)
• Mammaglobin has a role in progression of breast cancer, as shown by its expression in leukapheresis products (PMID:15447988)
• MGA protein exists in 2 main forms in breast neoplasms (PMID:15609337)
• occult blood hMAM mRNA can be detected by RT-PCR and may have a role in progression of breast neoplasms (PMID:16110760)
• mammaglobin expression is associated with expression of estrogen receptor and progesteron receptor in metastasizing breast cancer [letter] (PMID:16203799)
• MGB1 transcript in peripheral blood of breast cancer patients was specific but with low sensitivity. MGB1 overexpression by itself or in combination with Ki67 might be considered an index of breast cancer rogression (PMID:16760290)
• mammaglobin mRNA is expressed in breast cancer tissue (PMID:16761620)
• Mammaglobin A is a highly specific molecular marker for the detection of circulating tumor cells in operable breast cancer, with important prognostic applications. (PMID:16925986)
• Molecular staging of SLN using real-time RT-PCR for early breast cancer could serve as a useful complement to standard clinicopathological risk factors. (PMID:17071045)
• MGB1 immunohistochemistry can serve as a differential marker of breast cancer metastasis from primary lung cancer. (PMID:17192791)
• successfully generated MGB-specific CD4 T cell cultures and identified candidate MGB HLA class II epitopes (PMID:17653857)
• The sensitivity of mammaglobin is equal or superior to that of GCDFP-15 for investigation of breast carcinoma. (PMID:18251583)
• mammaglobin mRNA in peripheral blood may have a role in progression of breast cancer (PMID:18289390)
• RT-PCR for hMAM test was more sensitive than cytomorphology of breast cancer derived pleural effusion. (PMID:18303409)
• Expression levels of mammaglobins A and B in nasal polyps are not different between patients with and without AR (PMID:18416968)
• The detection of peripheral blood CK19mRNA+ and MGB1mRNA+ cells before adjuvant chemotherapy predicts poor DFS in women with early breast cancer. (PMID:18451221)
• The overexpression of mammaglobin observed in certain breast tumors is an epiphenomenon not causally involved in breast carcinogenesis. (PMID:18630503)
• This study demonstrated that human mammaglobin transcripts are expressed in the CSF of a BC patient with LM carcinomatosis. (PMID:18841443)
• Breast cancer patients with pre-operative elevated bone marrow levels of Mammaglobin Aand/or trefoil factor 1 mRNA seem to constitute a small group of patients with a very poor prognosis. (PMID:18846421)
• Both MGB1 and GCDFP-15 are specific markers for metastatic breast carcinomas in cell block fluid specimens (88 vs. 96%). (PMID:19217055)
• Mammaglobin is a sensitive marker of breast carcinoma, it defines a subgroup of patients with better prognosis and is a useful method to detect breast cancer metastases. (PMID:19690758)
• detection of mammaglobin mRNA is useful to determine the effect of therapy while maspin transcripts may indicate more aggressive disease. (PMID:20092039)
• 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)
• Detection of Mammaglobin as part of a 3-marker RT-PCR for early diagnosis of breast cancer. (PMID:20586026)
• Results showed the prognostic relevance of bone marrow disseminated tumor cells assessed by a multimarker mRNA panel consisting of TWIST1, cytokeratin 19 (gene name: KRT19), and mammaglobin A (gene name: SCGB2A2) mRNA in operable breast cancer patients. (PMID:20920982)
• Most basal-like breast carcinomas and unclassified triple-negative carcinomas are negative for mammaglobin and gross cystic disease fluid protein 15. (PMID:21411781)
• The current knowledge regarding the use of reverse-transcriptase PCR for detecting human mammaglobin mRNA as a biomarker for circulating tumor cells in breast cancer patients, is reviewed. (PMID:21473729)
• The expression of hMAG was found to be increased with breast cancer grade. (PMID:21623075)
• High serum mammaglobin is associated with breast cancer. (PMID:21744998)
• MGA detection by the modified nested RT-PCR is a specific marker for circulating tumor cells in patients with breast carcinoma and a negative prognostic factor for the disease (PMID:21939647)
• A decrease in MGB1+mRNA levels (baseline-week 8) seemed to be associated with clinical response (P = 0.05). (PMID:21976532)
• Data show that HLA-A24-restricted, mammaglobin-A (Mam-A) derived, CD8(+) cytotoxic T lymphocyte (CTL) epitopes that can potentially be employed for Mam-A-based breast cancer vaccine therapy to breast cancer patients with HLA-A24 phenotype. (PMID:22074997)
• High peripheral blood mammaglobin gene expression is associated with metastasis in breast cancer. (PMID:22897908)
• Gross cystic disease fluid protein-15 and mammaglobin A expression determined by immunohistochemistry is of limited utility in triple-negative breast cancer. (PMID:22963676)
• MGB1 was detected in endometrial tissue, with peak expression during the luteal phase, in 31% of endometriotic samples, in 53% of endometrial adenocarcinomas, and in 64% of breast carcinomas. (PMID:22994369)
• Qualitative detection of plasma hMAM mRNA appears to be associated with unfavorable prognostic factors and lower rates of event-free survival in patients with breast cancer. (PMID:23212340)
• Mammaglobin immunohistochemistry is useful as a proxy marker for the ETV6-NTRK3 translocation in the diagnosis of salivary mammary analogue secretory carcinoma. (PMID:23773480)
• Mammaglobin-A immunohistochemistry in primary central nervous system neoplasms and intracranial metastatic breast carcinoma. Cimino PJ Jr, Perrin RJ (PMID:23958549)
• Overexpression of hMAM in breast cancer cells decreased migration and invasion, whereas knockdown of hMAM increased both. (PMID:24328556)

Cross-species orthologs

3 orthologs

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

Paralogs (1): SCGB2A1 (ENSG00000124939)

Protein

Protein identifiers

Mammaglobin-A — Q13296 (reviewed: Q13296)

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

All UniProt accessions (2): Q13296, Q6NX70

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Tissue specificity. Mammary gland specific. Over-expressed in breast cancer.

Similarity. Belongs to the secretoglobin family. Lipophilin subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q13296-1	1	yes
Q13296-2	2

RefSeq proteins (1): NP_002402* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016126	Secretoglobin	Family
IPR035960	Secretoglobin_sf	Homologous_superfamily

Pfam: PF01099

UniProt features (5 total): glycosylation site 2, signal peptide 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13296-F1	89.38	0.67

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 (2): 53, 68

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 57 (showing top): GOBP_CELLULAR_RESPONSE_TO_LIPID, JAEGER_METASTASIS_DN, BECKER_TAMOXIFEN_RESISTANCE_UP, SMID_BREAST_CANCER_RELAPSE_IN_LUNG_DN, CROONQUIST_NRAS_SIGNALING_UP, GOBP_HORMONE_MEDIATED_SIGNALING_PATHWAY, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, GOBP_RESPONSE_TO_STEROID_HORMONE, GOBP_RESPONSE_TO_HORMONE, GOBP_RESPONSE_TO_LIPID, TURASHVILI_BREAST_DUCTAL_CARCINOMA_VS_DUCTAL_NORMAL_DN, GOBP_CELLULAR_RESPONSE_TO_STEROID_HORMONE_STIMULUS, GOBP_INTRACELLULAR_RECEPTOR_SIGNALING_PATHWAY, GOBP_STEROID_HORMONE_RECEPTOR_SIGNALING_PATHWAY, RIGGINS_TAMOXIFEN_RESISTANCE_DN

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

430 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SCGB2A2	MUCL1	Q96DR8	944
SCGB2A2	SCGB1D2	O95969	879
SCGB2A2	SCGB1A1	P11684	735
SCGB2A2	ETV4	P43268	691
SCGB2A2	ERBB2	P04626	669
SCGB2A2	PIP	P12273	543
SCGB2A2	KRT19	P08727	507
SCGB2A2	MUC1	P13931	505
SCGB2A2	SCGB1D1	O95968	476
SCGB2A2	TFF1	P04155	411
SCGB2A2	ANKRD30A	Q9BXX3	410
SCGB2A2	HMGN5	P82970	388
SCGB2A2	EPCAM	P16422	371
SCGB2A2	CEACAM5	P06731	367
SCGB2A2	SCGB2A1	O75556	360

IntAct

9 interactions, top by confidence:

A	B	Type	Score
SCGB2A2	VASP	psi-mi:“MI:0915”(physical association)	0.560
VASP	SCGB2A2	psi-mi:“MI:0915”(physical association)	0.560
CASP8	SCGB2A2	psi-mi:“MI:0915”(physical association)	0.370
CDKN2C	SCGB2A2	psi-mi:“MI:0915”(physical association)	0.370
LSP1	SCGB2A2	psi-mi:“MI:0915”(physical association)	0.370
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	RTL8C	psi-mi:“MI:0914”(association)	0.350

BioGRID (263): VASP (Two-hybrid), SCGB2A2 (Two-hybrid), SCGB2A2 (Two-hybrid), SCGB2A2 (Two-hybrid), SEMA3C (Affinity Capture-MS), CHST3 (Affinity Capture-MS), SEMA4D (Affinity Capture-MS), NXPE3 (Affinity Capture-MS), ECEL1 (Affinity Capture-MS), TPST1 (Affinity Capture-MS), GNPAT (Affinity Capture-MS), GLB1L (Affinity Capture-MS), ERN1 (Affinity Capture-MS), NDST2 (Affinity Capture-MS), EOGT (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.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	14
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

305 predictions. Top by Δscore:

Variant	Effect	Δscore
11:62270268:GCAG:G	donor_gain	1.0000
11:62270269:CAG:C	donor_gain	1.0000
11:62270272:G:GG	donor_gain	1.0000
11:62270272:GTGA:G	donor_loss	1.0000
11:62270875:TCCCA:T	acceptor_loss	1.0000
11:62270876:CCCAG:C	acceptor_loss	1.0000
11:62270878:CAGG:C	acceptor_loss	1.0000
11:62270880:G:GC	acceptor_loss	1.0000
11:62271015:G:GT	donor_gain	1.0000
11:62271016:A:T	donor_gain	1.0000
11:62270267:CGCAG:C	donor_gain	0.9900
11:62270268:GCAGG:G	donor_gain	0.9900
11:62270270:AG:A	donor_gain	0.9900
11:62270271:GG:G	donor_gain	0.9900
11:62270273:T:A	donor_loss	0.9900
11:62270879:A:AG	acceptor_gain	0.9900
11:62270879:AG:A	acceptor_gain	0.9900
11:62270880:G:GA	acceptor_gain	0.9900
11:62270880:GG:G	acceptor_gain	0.9900
11:62270880:GGCT:G	acceptor_gain	0.9900
11:62270880:GGCTC:G	acceptor_gain	0.9900
11:62270870:A:AG	acceptor_gain	0.9800
11:62270871:T:G	acceptor_gain	0.9800
11:62271055:TTG:T	donor_gain	0.9800
11:62270272:G:T	donor_gain	0.9700
11:62270867:T:TA	acceptor_gain	0.9600
11:62271055:T:G	donor_gain	0.9600
11:62271064:TTATG:T	donor_loss	0.9600
11:62271065:TATGG:T	donor_loss	0.9600
11:62271067:TGGTA:T	donor_loss	0.9600

AlphaMissense

622 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:62271014:G:C	K63N	0.913
11:62271014:G:T	K63N	0.913
11:62270970:T:C	F49L	0.877
11:62270972:C:A	F49L	0.877
11:62270972:C:G	F49L	0.877
11:62271021:T:C	F66L	0.820
11:62271023:T:A	F66L	0.820
11:62271023:T:G	F66L	0.820
11:62272972:A:C	S87R	0.777
11:62272974:C:A	S87R	0.777
11:62272974:C:G	S87R	0.777
11:62270997:G:C	A58P	0.761
11:62270950:A:C	Y42S	0.756
11:62270949:T:C	Y42H	0.755
11:62271013:A:C	K63T	0.702
11:62270949:T:G	Y42D	0.669
11:62271022:T:G	F66C	0.660
11:62271025:T:C	L67P	0.642
11:62271010:T:C	L62S	0.641
11:62271013:A:T	K63M	0.637
11:62270962:T:A	L46H	0.624
11:62270950:A:G	Y42C	0.619
11:62271032:A:C	Q69H	0.618
11:62271032:A:T	Q69H	0.618
11:62270889:T:C	C22R	0.616
11:62270954:A:C	K43N	0.611
11:62270954:A:T	K43N	0.611
11:62271022:T:C	F66S	0.607
11:62270911:T:G	I29S	0.606
11:62271046:T:C	L74P	0.598

dbSNP variants (sampled 300 via entrez): RS1000835530 (11:62269841 C>A,G), RS1001495159 (11:62269175 C>T), RS1001510635 (11:62269578 C>T), RS1001736330 (11:62268914 T>C), RS1001862705 (11:62269738 A>G), RS1003501337 (11:62271688 A>T), RS1003551743 (11:62268382 C>T), RS1004252982 (11:62273406 G>C), RS1004694111 (11:62269451 C>A), RS1005208473 (11:62269015 T>C), RS1005362868 (11:62269216 C>T), RS1007242941 (11:62270868 G>A,C), RS1008512328 (11:62271910 C>A,T), RS1008656587 (11:62272043 A>G,T), RS1009383619 (11:62272645 C>A,T)

Disease associations

OMIM: gene MIM:605562 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
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
GCST002976_7	HIV-1 viral setpoint	7.000000e-07
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 (5, from GWAS)

EFO ID	Trait name
EFO:0005680	omega-6 polyunsaturated fatty acid measurement
EFO:0006319	HIV viral set point 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

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects cotreatment, increases expression	2
Nickel	decreases expression	2
3-hydroxy-4-prenyl-5-methoxystilbene-2-carboxylic acid	decreases expression	1
Zoledronic Acid	increases expression	1
Arsenic Trioxide	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Progesterone	increases expression, affects cotreatment	1
Tetrachlorodibenzodioxin	increases expression	1
Tretinoin	decreases expression	1

Clinical trials (associated diseases)

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