SCGB3A2

Summary

SCGB3A2 (secretoglobin family 3A member 2, HGNC:18391) is a protein-coding gene on chromosome 5q32, encoding Secretoglobin family 3A member 2 (Q96PL1). Secreted cytokine-like protein.

The protein encoded by this gene is a secreted lung surfactant protein and a downstream target of thyroid transcription factor. A single nucleotide polymorphism in the promoter of this gene results in susceptibility to asthma.

Source: NCBI Gene 117156 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 14 total
• Phenotypes (HPO): 5
• MANE Select transcript: NM_054023

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18391
Approved symbol	SCGB3A2
Name	secretoglobin family 3A member 2
Location	5q32
Locus type	gene with protein product
Status	Approved
Aliases	UGRP1, LU103, PNSP1
Ensembl gene	ENSG00000164265
Ensembl biotype	protein_coding
OMIM	606531
Entrez	117156

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 19 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000296694, ENST00000504320, ENST00000507160, ENST00000514688, ENST00000937175, ENST00000937176, ENST00000937177, ENST00000937178, ENST00000937179, ENST00000937180, ENST00000937181, ENST00000937182, ENST00000937183, ENST00000937184, ENST00000937185, ENST00000937186, ENST00000937187, ENST00000937188, ENST00000937189, ENST00000937190, ENST00000937191

RefSeq mRNA: 1 — MANE Select: NM_054023 NM_054023

CCDS: CCDS4287

Canonical transcript exons

ENST00000296694 — 3 exons

Exon	Start	End
ENSE00001202058	147878711	147878858
ENSE00003609248	147881446	147881648
ENSE00003848922	147882027	147882191

Expression profiles

Bgee: expression breadth ubiquitous, 154 present calls, max score 99.52.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 12.4273 / max 12445.4730, expressed in 86 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
59254	12.2307	35
59253	0.1580	48
203733	0.0387	25

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
trachea	UBERON:0003126	99.52	gold quality
right lung	UBERON:0002167	98.96	gold quality
lower lobe of lung	UBERON:0008949	97.78	gold quality
adult organism	UBERON:0007023	97.64	gold quality
lung	UBERON:0002048	96.93	gold quality
upper lobe of lung	UBERON:0008948	96.28	gold quality
upper lobe of left lung	UBERON:0008952	96.21	gold quality
oocyte	CL:0000023	91.71	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.82	gold quality
visceral pleura	UBERON:0002401	86.30	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.03	gold quality
secondary oocyte	CL:0000655	84.73	gold quality
amniotic fluid	UBERON:0000173	83.66	gold quality
ascending aorta	UBERON:0001496	80.75	gold quality
thoracic aorta	UBERON:0001515	79.84	gold quality
bronchus	UBERON:0002185	78.31	gold quality
bronchial epithelial cell	CL:0002328	77.77	gold quality
calcaneal tendon	UBERON:0003701	73.62	gold quality
aorta	UBERON:0000947	72.13	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	70.20	gold quality
descending thoracic aorta	UBERON:0002345	68.22	gold quality
popliteal artery	UBERON:0002250	66.63	gold quality
tibial artery	UBERON:0007610	66.63	gold quality
left coronary artery	UBERON:0001626	62.35	gold quality
lower esophagus mucosa	UBERON:0035834	62.25	gold quality
monocyte	CL:0000576	62.16	gold quality
right coronary artery	UBERON:0001625	62.11	gold quality
leukocyte	CL:0000738	61.96	gold quality
skin of leg	UBERON:0001511	61.67	gold quality
tendon	UBERON:0000043	61.54	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-8221	yes	250591.64
E-HCAD-15	yes	37349.40
E-MTAB-6308	yes	30142.53
E-GEOD-130148	yes	19848.08
E-MTAB-10662	yes	19129.43
E-HCAD-1	yes	21.25
E-GEOD-86618	no	5749.19
E-MTAB-7008	no	295.99
E-MTAB-10018	no	257.55
E-GEOD-109979	no	207.28
E-MTAB-9801	no	2.58
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, CEBPD, NKX2-1, STAT3

miRNA regulators (miRDB)

13 targeting SCGB3A2, 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-4692	100.00	67.32	2066
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-4650-3P	99.01	68.39	1062
HSA-MIR-4773	98.35	67.30	1710
HSA-MIR-10395-3P	98.10	66.70	1726
HSA-MIR-1912-5P	97.94	67.98	832
HSA-MIR-2355-3P	96.84	68.54	909
HSA-MIR-2909	96.36	67.30	562
HSA-MIR-4761-3P	96.27	66.26	524

Literature-anchored findings (GeneRIF, showing 16)

• polymorphism in the human UGRP1 gene promoter that regulates transcription is associated with an increased risk of asthma (PMID:11813133)
• By in situ hybridization, UGRP1 is found to be expressed by lung Clara-like cells in the bronchial epithelium and up-regulated in lung epithelium of a patient with cystic fibrosis. (PMID:12847263)
• results demonstrate that interleukin-10 induces uteroglobin related protein 1(UGRP1) gene expression in lung epithelial cells through transcription factor T/EBP/NKX2.1-dependent pathway (PMID:15485815)
• plasma UGRP1 levels were associated with the G-112A UGRP1 gene promoter polymorphism and the severity of asthma (PMID:18089940)
• results suggest that the -112G/A polymorphism does not play a significant role in the genetic predisposition of the UGRP1 gene in atopic asthma in the Sicilian population (PMID:18201431)
• SCGB3A2 gene may contribute to Graves’ disease susceptibility. (PMID:19126779)
• association was detected between SCGB3A2 and U.K. Caucasian Graves’ disease subjects but the size of effect was smaller than that seen in the Oriental population (odds ratio = 1.28-1.73). (PMID:20210668)
• Results demonstrate that SCGB3A2 is a useful marker for diagnosis of pulmonary tumors both in mice and humans. (PMID:20466451)
• pattern of UGRP-1 concentration resembled that of Clara cell protein, both proteins occurring in high concentrations in amniotic fluid, sputum and BALF and in much lower concentrations in serum and urine (PMID:20843168)
• the SCGB3A2 -112G >A polymorphism may be considered as a likely marker linking susceptibility to allergy/asthma and Graves’ disease (PMID:21170691)
• Reduced production of UGRP1, which is likely due, at least in part, to a local cytokine environment, may contribute to the hyper-inflammation in chronic rhinosinusitis and correlates with response to surgery. (PMID:21385388)
• This study documents the association between polymorphisms in UGRP1 and the common cold, suggesting a potential role in its pathogenesis. (PMID:21410962)
• This meta-analysis suggests that SCGB3A2 polymorphism at positions -112G>A was associated with Graves’ disease both in Chinese and Caucasian population. (PMID:23934357)
• rs151333009 SNP showed a monomorphic genotype. Two promoter SNPs (rs6882292, -659 G/A and rs1368408, -112 G/A) showed significant association with asthma. These results suggest that the promoter SNPs (rs6882292 and rs1368408) of SCGB3A2 gene may contribute to susceptibility to asthma in a Korean population. (PMID:28422086)
• UGRP1 may be a novel marker in thyrocytes to predict Grave’s disease patients who develop hypothyroidism. (PMID:31255731)
• Emerging role of an immunomodulatory protein secretoglobin 3A2 in human diseases. (PMID:35016921)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Scgb3a2	ENSMUSG00000038791
rattus_norvegicus	Scgb3a2	ENSRNOG00000026912

Paralogs (1): SCGB3A1 (ENSG00000161055)

Protein

Protein identifiers

Secretoglobin family 3A member 2 — Q96PL1 (reviewed: Q96PL1)

Alternative names: Pneumo secretory protein 1, Uteroglobin-related protein 1

All UniProt accessions (3): D6RBX5, Q96PL1, Q2L6B3

UniProt curated annotations — full annotation on UniProt →

Function. Secreted cytokine-like protein. Binds to the scavenger receptor MARCO. Can also bind to pathogens including the Gram-positive bacterium L.monocytogenes, the Gram-negative bacterium P.aeruginosa, and yeast. Strongly inhibits phospholipase A2 (PLA2G1B) activity. Seems to have anti-inflammatory effects in respiratory epithelium. Also has anti-fibrotic activity in lung. May play a role in fetal lung development and maturation. Promotes branching morphogenesis during early stages of lung development. In the pituitary, may inhibit production of follicle-stimulating hormone (FSH) and luteinizing hormone (LH).

Subunit / interactions. Homodimer; disulfide-linked. Monomer. Interacts with APOA1.

Subcellular location. Secreted.

Tissue specificity. Highly expressed in lung and trachea. Detected throughout the airway epithelium in lung, with slightly higher expression in large airways. Found in lung submucosal gland acinus where it localizes to serous-like cells. Probably expressed in club cells of the bronchioles. Not detected in other tissues tested.

Similarity. Belongs to the secretoglobin family. UGRP subfamily.

RefSeq proteins (1): NP_473364* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR040301	Secretoglobin_3A	Family

Pfam: PF20490

UniProt features (4 total): signal peptide 1, chain 1, disulfide bond 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96PL1-F1	74.66	0.00

Functional residue map

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

Disulfide bonds (1): 70

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-3000480	Scavenging by Class A Receptors
R-HSA-2173782	Binding and Uptake of Ligands by Scavenger Receptors
R-HSA-5653656	Vesicle-mediated transport

MSigDB gene sets: 47 (showing top): MODULE_95, MCDOWELL_ACUTE_LUNG_INJURY_DN, chr5q32, GOCC_ENDOCYTIC_VESICLE, GOCC_ENDOCYTIC_VESICLE_LUMEN, BENPORATH_ES_1, MODULE_49, MODULE_163, MTOR_UP.V1_UP, REACTOME_BINDING_AND_UPTAKE_OF_LIGANDS_BY_SCAVENGER_RECEPTORS, REACTOME_SCAVENGING_BY_CLASS_A_RECEPTORS, REACTOME_VESICLE_MEDIATED_TRANSPORT, SETD7_TARGET_GENES, MIR4761_3P, MIR2909

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (3): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), endocytic vesicle lumen (GO:0071682)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Binding and Uptake of Ligands by Scavenger Receptors	1
Vesicle-mediated transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	1
endocytic vesicle	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

552 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SCGB3A2	SCGB1A1	P11684	860
SCGB3A2	FOXJ1	Q92949	763
SCGB3A2	SFTPA2	P07714	725
SCGB3A2	NKX2-1	P43699	695
SCGB3A2	SFTPC	P11686	656
SCGB3A2	SCGB2A1	O75556	623
SCGB3A2	SFTPB	P07988	605
SCGB3A2	PLA2G7	Q13093	547
SCGB3A2	KCNS3	Q9BQ31	547
SCGB3A2	KRT5	P13647	546
SCGB3A2	SCGB1C1	Q8TD33	506
SCGB3A2	MUC7	Q8TAX7	499
SCGB3A2	PHF11	Q9UIL8	495
SCGB3A2	PTGDR2	Q9Y5Y4	495
SCGB3A2	HNMT	P50135	494

IntAct

0 interactions, top by confidence:

BioGRID (1): SCGB3A2 (FRET)

ESM2 similar proteins: A0JPN3, A2BGH0, G3HIK4, O09051, O42273, P07743, P11597, P17559, P22687, P25914, P28902, P33680, P47896, P59826, P59827, P70664, P70668, P79124, P79125, P79897, P82615, P97361, Q02747, Q05701, Q05704, Q28358, Q2VPS3, Q5XW65, Q61114, Q63471, Q63751, Q80XI7, Q80ZU7, Q865V1, Q86YQ2, Q8C186, Q8C1E1, Q8K4I4, Q8N4F0, Q8R5G8

Diamond homologs: Q920D7, Q920H1, Q96PL1, Q96QR1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	12
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

356 predictions. Top by Δscore:

Variant	Effect	Δscore
5:147878860:TAA:T	donor_loss	1.0000
5:147881444:A:AG	acceptor_gain	1.0000
5:147881445:G:GA	acceptor_gain	1.0000
5:147881445:GCT:G	acceptor_gain	1.0000
5:147881445:GCTA:G	acceptor_gain	1.0000
5:147881594:G:GT	donor_gain	1.0000
5:147878854:CTCTG:C	donor_gain	0.9900
5:147878859:G:GG	donor_gain	0.9900
5:147881442:GCA:G	acceptor_loss	0.9900
5:147881443:CAG:C	acceptor_loss	0.9900
5:147881445:GC:G	acceptor_gain	0.9900
5:147881445:GCTAC:G	acceptor_gain	0.9900
5:147881586:GGGC:G	donor_gain	0.9900
5:147881683:G:T	donor_gain	0.9900
5:147878855:TCTG:T	donor_gain	0.9800
5:147878856:CTG:C	donor_gain	0.9800
5:147879107:A:AG	donor_gain	0.9800
5:147879107:A:G	donor_gain	0.9800
5:147878857:TG:T	donor_gain	0.9700
5:147878858:GG:G	donor_gain	0.9700
5:147881441:T:TA	acceptor_gain	0.9700
5:147881569:T:G	donor_gain	0.9700
5:147881587:GGC:G	donor_gain	0.9400
5:147881667:GC:G	donor_gain	0.9200
5:147881664:G:GT	donor_gain	0.8900
5:147881664:G:T	donor_gain	0.8600
5:147878817:C:G	donor_gain	0.8500
5:147879060:AT:A	donor_gain	0.8500
5:147879067:A:T	acceptor_gain	0.8500
5:147881663:G:GT	donor_gain	0.8500

AlphaMissense

587 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:147881563:T:C	I58T	0.979
5:147881590:T:C	L67P	0.976
5:147878840:A:C	S13R	0.963
5:147878842:C:A	S13R	0.963
5:147878842:C:G	S13R	0.963
5:147881644:T:C	L85P	0.963
5:147881586:G:A	G66R	0.958
5:147881586:G:C	G66R	0.958
5:147881563:T:G	I58S	0.955
5:147881560:G:T	G57V	0.952
5:147881586:G:T	G66W	0.950
5:147882034:T:C	L89P	0.950
5:147881590:T:G	L67R	0.946
5:147881644:T:A	L85Q	0.945
5:147881536:T:C	L49S	0.941
5:147881611:T:C	L74P	0.933
5:147878849:A:C	S16R	0.932
5:147878851:T:A	S16R	0.932
5:147878851:T:G	S16R	0.932
5:147881578:T:A	L63H	0.926
5:147881647:T:C	L86P	0.922
5:147882034:T:A	L89Q	0.916
5:147881590:T:A	L67Q	0.915
5:147878846:T:C	C15R	0.914
5:147881548:T:A	L53Q	0.913
5:147881559:G:C	G57R	0.912
5:147881644:T:G	L85R	0.910
5:147881557:T:C	L56P	0.906
5:147881611:T:A	L74Q	0.901
5:147881559:G:T	G57C	0.900

dbSNP variants (sampled 300 via entrez): RS1001384711 (5:147880779 C>T), RS1001958380 (5:147879125 C>A,T), RS1002072924 (5:147879402 C>G), RS1002458498 (5:147881409 A>G), RS1002939453 (5:147878894 T>G), RS1003017515 (5:147881938 G>A,C), RS1003186814 (5:147877283 T>C), RS1003275186 (5:147877623 T>A), RS1003493830 (5:147882442 A>G), RS1004310659 (5:147881845 T>C), RS1004343272 (5:147881460 A>T), RS1005228262 (5:147877644 C>T), RS10058203 (5:147879479 G>A), RS1005859056 (5:147882239 G>A,T), RS1006525646 (5:147879972 T>C,G)

Disease associations

OMIM: gene MIM:606531 | disease phenotypes: MIM:600807

GenCC curated gene-disease

Mondo (1): inherited susceptibility to asthma (MONDO:0010940)

Orphanet (0):

HPO phenotypes

5 total (5 of 5 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001426	Non-Mendelian inheritance
HP:0002099	Asthma
HP:0032933	Airway hyperresponsiveness
HP:4000007	Bronchoconstriction

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST004860_95	Alcoholic chronic pancreatitis	3.000000e-15

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, affects cotreatment, increases expression	8
trichostatin A	affects cotreatment, increases expression	3
entinostat	increases expression, affects cotreatment	2
belinostat	affects cotreatment, increases expression	2
Panobinostat	increases expression, affects cotreatment	2
methylmercuric chloride	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Carbamazepine	affects expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Diethylhexyl Phthalate	increases expression	1
Tretinoin	affects expression	1
Cyclosporine	increases methylation	1
Aflatoxin B1	decreases methylation	1
Lactic Acid	increases expression	1

Clinical trials (associated diseases)

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