SCGB3A1

Summary

SCGB3A1 (secretoglobin family 3A member 1, HGNC:18384) is a protein-coding gene on chromosome 5q35.3, encoding Secretoglobin family 3A member 1 (Q96QR1). Secreted cytokine-like protein.

Predicted to enable cytokine activity. Predicted to be involved in positive regulation of myoblast fusion. Located in extracellular space.

Source: NCBI Gene 92304 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 17 total
• MANE Select transcript: NM_052863

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18384
Approved symbol	SCGB3A1
Name	secretoglobin family 3A member 1
Location	5q35.3
Locus type	gene with protein product
Status	Approved
Aliases	UGRP2, HIN-1, HIN1, LU105, PnSP-2
Ensembl gene	ENSG00000161055
Ensembl biotype	protein_coding
OMIM	606500
Entrez	92304

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 retained_intron

ENST00000292641, ENST00000512120, ENST00000899434

RefSeq mRNA: 1 — MANE Select: NM_052863 NM_052863

CCDS: CCDS4456

Canonical transcript exons

ENST00000292641 — 3 exons

Exon	Start	End
ENSE00001150375	180590600	180590838
ENSE00001295334	180591411	180591499
ENSE00002063582	180590105	180590254

Expression profiles

Bgee: expression breadth ubiquitous, 177 present calls, max score 99.98.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 19.3206 / max 11568.1469, expressed in 115 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
65307	18.6176	71
65308	0.1935	32
65304	0.1424	19
65310	0.1084	43
65311	0.0972	35
65309	0.0391	15
65306	0.0309	8
65303	0.0300	14
65305	0.0271	13
65312	0.0187	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
trachea	UBERON:0003126	99.98	gold quality
bronchial epithelial cell	CL:0002328	99.97	gold quality
bronchus	UBERON:0002185	99.97	gold quality
parotid gland	UBERON:0001831	99.93	gold quality
pancreatic ductal cell	CL:0002079	99.89	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.89	gold quality
right lung	UBERON:0002167	99.27	gold quality
urethra	UBERON:0000057	98.48	gold quality
palpebral conjunctiva	UBERON:0001812	98.46	gold quality
adult organism	UBERON:0007023	98.25	gold quality
nasal cavity mucosa	UBERON:0001826	98.20	gold quality
lower lobe of lung	UBERON:0008949	96.86	gold quality
saliva-secreting gland	UBERON:0001044	94.98	gold quality
upper lobe of lung	UBERON:0008948	94.61	gold quality
upper lobe of left lung	UBERON:0008952	94.40	gold quality
nasal cavity epithelium	UBERON:0005384	93.85	gold quality
minor salivary gland	UBERON:0001830	93.83	gold quality
epithelial cell of pancreas	CL:0000083	92.86	silver quality
right uterine tube	UBERON:0001302	92.48	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.14	gold quality
lung	UBERON:0002048	91.23	gold quality
epithelium of mammary gland	UBERON:0003244	89.70	gold quality
mammary duct	UBERON:0001765	89.61	gold quality
pharyngeal mucosa	UBERON:0000355	89.19	gold quality
mouth mucosa	UBERON:0003729	88.82	gold quality
mammary gland	UBERON:0001911	83.85	gold quality
thoracic mammary gland	UBERON:0005200	83.66	gold quality
visceral pleura	UBERON:0002401	82.86	gold quality
pituitary gland	UBERON:0000007	82.29	gold quality
tongue	UBERON:0001723	81.79	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-MTAB-8221	yes	454911.65
E-HCAD-15	yes	151258.64
E-MTAB-6653	yes	117308.34
E-MTAB-6308	yes	113525.71
E-CURD-114	yes	85368.79
E-GEOD-130148	yes	67512.20
E-MTAB-8495	yes	24180.35
E-GEOD-86618	yes	2861.25
E-HCAD-1	yes	23.01
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EPAS1, NKX2-1, STAT1, STAT3, STAT5A, STAT6, TTF1

miRNA regulators (miRDB)

3 targeting SCGB3A1, 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-3934-5P	99.67	64.04	846
HSA-MIR-3179	98.22	65.90	1445
HSA-MIR-3655	86.11	61.77	117

Literature-anchored findings (GeneRIF, showing 29)

• Sporadic breast tumors with a “BRCA1-like” histopathological phenotype also demonstrated significantly lower frequency of HIN-1 promoter methylation. (PMID:12727813)
• hypermethylated in invasive and in in situ lobular breast cancer (PMID:14601057)
• Lack of HIN-1 methylation defines specific breast tumor subtypes including medullary carcinoma of the breast and BRCA1-linked tumors (PMID:14614327)
• high in normal-1 (HIN-1) is downregulated in stage I non-small cell lung cancer (PMID:14977834)
• silencing of HIN-1 expression and methylation of its promoter occurs in multiple human cancer types, suggesting that elimination of HIN-1 function may contribute to several forms of epithelial tumorigenesis (PMID:15383627)
• Aberrant methylation of HIN-1 is a frequent event in many human malignancies (PMID:15472908)
• Studies provide further evidence that HIN-1 possesses tumor suppressor functions, and that these activities may be mediated through the AKT signaling pathway. (PMID:16266985)
• CASP8, DCR2, and HIN-1 methylation leads to progression of neuroblastoma (PMID:17545522)
• DNA hypermethylation of tumour suppressor genes seems to play an important role in ovarian carcinogenesis and HOXA9, HOXB5, SCGB3A1, and CRABP1 are identified as novel hypermethylated target genes in this tumour type (PMID:17623056)
• HIN-1 was strongly associated with breast cytologic atypia. HIN-1 methylation increased rapidly between ages 32 and 40. (PMID:18483325)
• HIN-1 silencing is associated with dense promoter region hypermethylation in esophageal cancer and suggest that methylation of HIN-1 is an early event in dysplastic transformation. (PMID:19098448)
• The combination of RARB M4, INK4a/ARF, PRB, and HIN-1 CpG island promoter methylation may predict non-BRCA1/2-associated mammary carcinogenesis and tumor progression. (PMID:19258476)
• Results show that cumulative RASSF1A, TWIST1, and HIN1 gene methylation accurately distinguished ducts with cancerous versus benign lesions. (PMID:19470737)
• The epigenetic silencing of tumor suppressor genes involved in the Ras/PI3K/AKT pathway plays an important role in oral squamous cell carcinoma radioresistance (PMID:19509163)
• HIN-1, RAR-beta, RASSF1A, and Twist had the ability to distinguish high-grade squamous intraepithelial lesions/squamous cell carcinomas from low-grade squamous intraepithelial lesions/negative cervical scrapings (PMID:20496080)
• The methylation levels and frequencies of HIN1, RASSF1A and TWIST, and average MR were significantly lower in basal-like subtype compared to luminal or human epithelial growth factor receptor-2 subtype. (PMID:20505321)
• Hypermethylation of HIN-1 is associated with lymphatic metastasis of breast cancers. (PMID:20642860)
• Data suggest that high methylation of the HIN-1 promoter results in silenced HIN-1 expression in gastric cancer, and that 5-aza-2’-deoxycytidine reverses HIN-1 methylation and reduces viability of gastric cancer cells. (PMID:21274384)
• Data show that SCGB3A1 was down-regulated in invasive compared with DCIS, whereas talin 2 (TLN2) and PTGS1 were up-regulated in invasive compared with DCIS. (PMID:21812955)
• HIN1, was the most “dietary sensitive” genes, as methylation of their promoters was associated with intakes of at least two out of the eight dietary methyl factors examined. (PMID:22048254)
• analysis of AKT signaling pathway activated by HIN-1 methylation in non-small cell lung cancer (PMID:22095135)
• Methylation of HIN-1, RASSF1A, RIL and CDH13 in breast cancers was associated with clinical characteristics, but only RASSF1A methylation was associated with time to first recurrence and overall survival. (PMID:22695491)
• Methylation of HIN-1 promoter is a novel epigenetic biomarker associated with poor outcomes in OCCA patients. (PMID:22871047)
• SCGB3A1-183 T and SCGB3A1 IVS1-189 A alleles might have a protective effect against nasal polyposis. (PMID:24710847)
• aberrant HIN-1 promoter methylation could be an independent and important biomarker used in predicting the prognosis and progression of breast cancer (PMID:24850174)
• The role of high in normal-1 (HIN-1) as a potential biomarker in combating glioblastoma is being described for the first time in this study. (PMID:25752997)
• Tumor-adjacent tissues showed higher methylation status of RASSF1A, HIN-1 and MGMT promoters. (PMID:26370119)
• Some single nucleotide polymorphisms and their combinations in the Ugrp2 gene are associated with an increased risk of developing adenoid hypertrophy. (PMID:28823693)
• HOXA9, RASSF1A and SCGB3A1 promoter methylation significantly associated with testicular germ cell tumor stage. (PMID:30418048)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Scgb3a1	ENSMUSG00000064057
rattus_norvegicus	Scgb3a1	ENSRNOG00000002718

Paralogs (1): SCGB3A2 (ENSG00000164265)

Protein

Protein identifiers

Secretoglobin family 3A member 1 — Q96QR1 (reviewed: Q96QR1)

Alternative names: Cytokine HIN-1, High in normal 1, Pneumo secretory protein 2, Uteroglobin-related protein 2

All UniProt accessions (1): Q96QR1

UniProt curated annotations — full annotation on UniProt →

Function. Secreted cytokine-like protein. Inhibits cell growth in vitro.

Subunit / interactions. Homodimer; disulfide-linked.

Subcellular location. Secreted.

Tissue specificity. Highly expressed in lung and prostate. Also found in mammary gland, spleen, pancreas, testis and liver. Detected throughout the airway epithelium in lung, with highest expression in large airways. Found in lung submucosal glands where it localizes to acinar and ductile cells. Not detected in respiratory bronchioles, alveolar ducts or alveolar epithelium. In mammary gland, specifically localizes to luminal epithelial cells.

Similarity. Belongs to the secretoglobin family. UGRP subfamily.

RefSeq proteins (1): NP_443095* (*=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 conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96QR1-F1	62.51	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): 78

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 74 (showing top): RNGTGGGC_UNKNOWN, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GOBP_GROWTH, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOBP_REGULATION_OF_SYNCYTIUM_FORMATION_BY_PLASMA_MEMBRANE_FUSION, ZIC1_01, GOMF_CYTOKINE_ACTIVITY, GOBP_MYOTUBE_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_16D_DN, GOMF_SIGNALING_RECEPTOR_BINDING, GOBP_CELL_GROWTH, GOBP_SYNCYTIUM_FORMATION, GOBP_MYOBLAST_FUSION

GO Biological Process (4): negative regulation of cell growth (GO:0030308), regulation of cell population proliferation (GO:0042127), positive regulation of myoblast fusion (GO:1901741), signal transduction (GO:0007165)

GO Molecular Function (2): cytokine activity (GO:0005125), protein binding (GO:0005515)

GO Cellular Component (3): obsolete extracellular space (GO:0005615), extracellular exosome (GO:0070062), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of cellular process	2
regulation of cell growth	1
cell growth	1
negative regulation of growth	1
negative regulation of cellular process	1
cell population proliferation	1
myoblast fusion	1
positive regulation of syncytium formation by plasma membrane fusion	1
regulation of myoblast fusion	1
cell communication	1
cellular process	1
signaling	1
cellular response to stimulus	1
receptor ligand activity	1
binding	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

544 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SCGB3A1	SCGB1A1	P11684	778
SCGB3A1	SFTPA2	P07714	597
SCGB3A1	RASSF1	Q9NS23	570
SCGB3A1	BPIFB1	Q8TDL5	539
SCGB3A1	CDH13	P55290	417
SCGB3A1	FOXJ1	Q92949	416
SCGB3A1	NKX2-1	P43699	413
SCGB3A1	RARB	P10826	412
SCGB3A1	SCGB1C1	Q8TD33	412
SCGB3A1	DLEC1	Q9Y238	411
SCGB3A1	GSTP1	P09211	397
SCGB3A1	BPIFA1	Q9NP55	386
SCGB3A1	CCND2	P30279	370
SCGB3A1	FAM240A	A0A1B0GVK7	370
SCGB3A1	SFTPC	P11686	370
SCGB3A1	MUC5B	Q9HC84	370

IntAct

12 interactions, top by confidence:

A	B	Type	Score
RHBDD2	SCGB3A1	psi-mi:“MI:0915”(physical association)	0.560
AURKA	SCGB3A1	psi-mi:“MI:0915”(physical association)	0.370
BAG4	SCGB3A1	psi-mi:“MI:0915”(physical association)	0.370
SCGB3A1	FBXW7	psi-mi:“MI:0915”(physical association)	0.370
SCGB3A1	FGFR4	psi-mi:“MI:0915”(physical association)	0.370
SCGB3A1	TGFB1	psi-mi:“MI:0915”(physical association)	0.370
TSG101	SCGB3A1	psi-mi:“MI:0915”(physical association)	0.370
XRCC3	SCGB3A1	psi-mi:“MI:0915”(physical association)	0.370
SCGB3A1	COL14A1	psi-mi:“MI:0914”(association)	0.350
SCGB3A1	RHBDD2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (14): SCGB3A1 (Reconstituted Complex), SCGB3A1 (Two-hybrid), SCGB3A1 (Two-hybrid), SCGB3A1 (Two-hybrid), SCGB3A1 (Two-hybrid), SCGB3A1 (Two-hybrid), SCGB3A1 (Two-hybrid), SCGB3A1 (Two-hybrid), SCGB3A1 (FRET), SCGB3A1 (Two-hybrid), COL14A1 (Affinity Capture-MS), STEAP3 (Affinity Capture-MS), ERMP1 (Affinity Capture-MS), SCCPDH (Affinity Capture-MS)

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

267 predictions. Top by Δscore:

Variant	Effect	Δscore
5:180590593:A:AC	donor_gain	0.9900
5:180590594:C:CC	donor_gain	0.9900
5:180590662:T:TA	donor_gain	0.9900
5:180590836:CAG:C	acceptor_gain	0.9900
5:180590839:C:CC	acceptor_gain	0.9900
5:180590515:AGGG:A	donor_gain	0.9800
5:180590659:A:AC	donor_gain	0.9800
5:180590660:C:CC	donor_gain	0.9800
5:180590660:CTT:C	donor_gain	0.9800
5:180590966:T:TA	donor_gain	0.9800
5:180591405:GCTCA:G	donor_loss	0.9700
5:180591406:CTCA:C	donor_loss	0.9700
5:180591407:TCA:T	donor_loss	0.9700
5:180591408:CA:C	donor_loss	0.9700
5:180591409:A:T	donor_loss	0.9700
5:180590251:CCCC:C	acceptor_gain	0.9600
5:180590252:CCC:C	acceptor_gain	0.9600
5:180590252:CCCC:C	acceptor_gain	0.9600
5:180590253:CCC:C	acceptor_gain	0.9600
5:180590254:CCTG:C	acceptor_loss	0.9600
5:180590255:CTGGA:C	acceptor_loss	0.9600
5:180590647:G:C	donor_gain	0.9600
5:180590835:GCAG:G	acceptor_gain	0.9600
5:180590836:CAGC:C	acceptor_gain	0.9600
5:180590963:C:CA	donor_gain	0.9600
5:180591403:GCGCT:G	donor_loss	0.9600
5:180591404:CGCTC:C	donor_loss	0.9600
5:180590256:T:A	acceptor_loss	0.9500
5:180590837:AGC:A	acceptor_loss	0.9500
5:180590840:T:A	acceptor_loss	0.9500

AlphaMissense

638 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:180590679:A:T	L71H	0.956
5:180590694:A:G	I66T	0.944
5:180590697:C:A	G65V	0.943
5:180590691:G:A	P67L	0.913
5:180591441:C:G	G8R	0.910
5:180591441:C:T	G8R	0.910
5:180590679:A:G	L71P	0.908
5:180590679:A:C	L71R	0.892
5:180590694:A:C	I66S	0.885
5:180590668:A:G	S75P	0.882
5:180591435:A:G	C10R	0.875
5:180590659:A:G	C78R	0.871
5:180590657:A:C	C78W	0.864
5:180590709:A:T	L61Q	0.864
5:180590698:C:A	G65C	0.863
5:180590698:C:G	G65R	0.862
5:180590712:A:C	L60R	0.859
5:180590671:C:G	G74R	0.858
5:180590644:C:G	G83R	0.849
5:180590709:A:C	L61R	0.837
5:180590613:A:G	L93P	0.836
5:180590709:A:G	L61P	0.836
5:180590700:A:G	L64P	0.832
5:180590236:C:G	G104R	0.826
5:180590653:C:G	A80P	0.825
5:180590667:G:A	S75F	0.822
5:180591440:C:T	G8E	0.822
5:180590721:A:C	L57R	0.821
5:180590721:A:G	L57P	0.818
5:180590646:A:G	L82P	0.815

dbSNP variants (sampled 300 via entrez): RS1000275961 (5:180591282 G>A), RS1000423769 (5:180593293 C>A), RS1000558855 (5:180590106 G>A,T), RS1000610987 (5:180590354 C>A,T), RS1000732168 (5:180591565 G>A,C), RS1001166218 (5:180590439 C>G,T), RS1001302085 (5:180590733 G>C), RS1002835019 (5:180591423 A>G), RS1002970445 (5:180593493 C>T), RS1003304577 (5:180592893 C>A,T), RS1004231068 (5:180592066 G>A), RS1004511330 (5:180590591 C>T), RS1004584487 (5:180591850 G>T), RS1004966004 (5:180590967 C>T), RS1005832587 (5:180589912 T>G)

Disease associations

OMIM: gene MIM:606500 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST006585_2489	Blood protein levels	4.000000e-07
GCST007483_21	Waist-to-hip ratio adjusted for BMI (additive genetic model)	9.000000e-06
GCST007492_18	Waist-to-hip ratio adjusted for BMI (additive genetic model)	1.000000e-06
GCST007494_10	Waist-to-hip ratio adjusted for BMI (additive genetic model)	7.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs307821	FLT4, SCGB3A1	3	2.25	1	sunitinib

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases abundance, increases expression, decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
bisphenol A	affects cotreatment, decreases methylation	1
Decitabine	decreases methylation, increases expression	1
Fulvestrant	decreases methylation, affects cotreatment	1
Arsenic	decreases methylation	1
Benzo(a)pyrene	decreases methylation	1
Smoke	decreases expression, increases abundance	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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