SCGB1D2

Summary

SCGB1D2 (secretoglobin family 1D member 2, HGNC:18396) is a protein-coding gene on chromosome 11q12.3, encoding Secretoglobin family 1D member 2 (O95969). May bind androgens and other steroids, may also bind estramustine, a chemotherapeutic agent used for prostate cancer.

The protein encoded by this gene is a member of the lipophilin subfamily, part of the uteroglobin superfamily, and is an ortholog of prostatein, the major secretory glycoprotein of the rat ventral prostate gland. Lipophilin gene products are widely expressed in normal tissues, especially in endocrine-responsive organs. Assuming that human lipophilins are the functional counterparts of prostatein, they may be transcriptionally regulated by steroid hormones, with the ability to bind androgens, other steroids and possibly bind and concentrate estramustine, a chemotherapeutic agent widely used for prostate cancer. Although the gene has been reported to be on chromosome 10, this sequence appears to be from a cluster of genes on chromosome 11 that includes mammaglobin 2.

Source: NCBI Gene 10647 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 25 total
• MANE Select transcript: NM_006551

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18396
Approved symbol	SCGB1D2
Name	secretoglobin family 1D member 2
Location	11q12.3
Locus type	gene with protein product
Status	Approved
Aliases	LPHB, LIPB
Ensembl gene	ENSG00000124935
Ensembl biotype	protein_coding
OMIM	615061
Entrez	10647

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000244926

RefSeq mRNA: 1 — MANE Select: NM_006551 NM_006551

CCDS: CCDS8017

Canonical transcript exons

ENST00000244926 — 3 exons

Exon	Start	End
ENSE00000851583	62243289	62243476
ENSE00001315540	62242239	62242362
ENSE00001684478	62244670	62244812

Expression profiles

Bgee: expression breadth ubiquitous, 175 present calls, max score 99.34.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.9875 / max 627.5738, expressed in 92 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
114680	0.4253	25
114682	0.3494	57
114681	0.1505	21
114678	0.0486	6
114679	0.0137	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	99.34	gold quality
upper leg skin	UBERON:0004262	99.14	gold quality
skin of leg	UBERON:0001511	96.74	gold quality
epithelium of mammary gland	UBERON:0003244	94.89	gold quality
corpus epididymis	UBERON:0004359	94.86	gold quality
upper arm skin	UBERON:0004263	94.85	gold quality
mammary duct	UBERON:0001765	94.71	gold quality
zone of skin	UBERON:0000014	94.19	gold quality
skin of hip	UBERON:0001554	94.05	gold quality
skin of abdomen	UBERON:0001416	93.36	gold quality
mammary gland	UBERON:0001911	88.49	gold quality
thoracic mammary gland	UBERON:0005200	88.44	gold quality
endometrium	UBERON:0001295	87.37	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	85.83	gold quality
cauda epididymis	UBERON:0004360	82.51	gold quality
minor salivary gland	UBERON:0001830	79.58	gold quality
epididymis	UBERON:0001301	79.37	gold quality
fallopian tube	UBERON:0003889	78.62	gold quality
choroid plexus epithelium	UBERON:0003911	77.09	gold quality
metanephros cortex	UBERON:0010533	76.97	gold quality
endocervix	UBERON:0000458	76.66	gold quality
adenohypophysis	UBERON:0002196	75.79	gold quality
mouth mucosa	UBERON:0003729	74.60	gold quality
gastrocnemius	UBERON:0001388	73.68	gold quality
saliva-secreting gland	UBERON:0001044	73.28	gold quality
muscle of leg	UBERON:0001383	72.36	gold quality
left uterine tube	UBERON:0001303	72.20	gold quality
oviduct epithelium	UBERON:0004804	71.76	gold quality
decidua	UBERON:0002450	71.75	silver quality
uterus	UBERON:0000995	70.03	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-10283	yes	10011.32
E-HCAD-38	yes	870.99
E-GEOD-99795	no	7.36
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

4 targeting SCGB1D2, 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-8062	99.88	68.43	995
HSA-MIR-17-3P	99.55	66.77	1311
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-616-3P	96.82	66.99	784

Literature-anchored findings (GeneRIF, showing 8)

• Serum antibodies to this protein are detected in late stage breast cancer patients. (PMID:12576445)
• The present report demonstrates, for the first time, lipophilin B expression in the pituitary and its apparent down-regulation in pituitary adenomas. (PMID:15668787)
• We conclude that expression of LPB is preferentially but not exclusively restricted to breast tissue. (PMID:17163411)
• Ectopic overexpression of mammaglobin and lipophilin B did not affect the cell proliferation rate of Hs578T breast carcinoma cells in vitro. (PMID:18630503)
• lipophilin B gene overexpression correlates with a less aggressive tumor phenotype and represents a novel ovarian carcinoma prognostic factor (PMID:23819652)
• 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)
• [Measurement of PODXL and SCGB1D2 for detecting intraductal papillary mucinous neoplasm]. (PMID:33692257)
• SCGB1D2 inhibits growth of Borrelia burgdorferi and affects susceptibility to Lyme disease. (PMID:38503741)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
rattus_norvegicus	Scgb1d2	ENSRNOG00000020294
rattus_norvegicus	Scgb1d4	ENSRNOG00000020301
rattus_norvegicus	AABR07006242.1	ENSRNOG00000028909
rattus_norvegicus		ENSRNOG00000074874

Paralogs (2): SCGB1D1 (ENSG00000168515), SCGB1D4 (ENSG00000197745)

Protein

Protein identifiers

Secretoglobin family 1D member 2 — O95969 (reviewed: O95969)

Alternative names: Lipophilin-B

All UniProt accessions (1): O95969

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.

Subcellular location. Secreted.

Tissue specificity. Highest expression was found in skeletal muscle. Expressed as well 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_006542* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016126	Secretoglobin	Family
IPR035960	Secretoglobin_sf	Homologous_superfamily

Pfam: PF01099

UniProt features (4 total): sequence variant 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95969-F1	90.52	0.66

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 39 (showing top): SMID_BREAST_CANCER_RELAPSE_IN_LUNG_DN, TURASHVILI_BREAST_DUCTAL_CARCINOMA_VS_DUCTAL_NORMAL_DN, DOANE_BREAST_CANCER_ESR1_UP, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, TGFB_UP.V1_DN, GREB1_TARGET_GENES, HOXB7_TARGET_GENES, ZIM3_TARGET_GENES, SMID_BREAST_CANCER_ERBB2_UP, MIR616_3P, SMID_BREAST_CANCER_RELAPSE_IN_BONE_UP, GSE1460_CORD_VS_ADULT_BLOOD_NAIVE_CD4_TCELL_UP, FAN_EMBRYONIC_CTX_BIG_GROUPS_CAJAL_RETZIUS, FARMER_BREAST_CANCER_APOCRINE_VS_LUMINAL, ZNF41_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (0):

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
cellular anatomical structure	1

Protein interactions and networks

STRING

384 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SCGB1D2	LIPA	P38571	960
SCGB1D2	SCGB2A2	Q13296	879
SCGB1D2	LIPC	P11150	761
SCGB1D2	SCGB2A1	O75556	695
SCGB1D2	LIPF	P07098	548
SCGB1D2	PNLIP	P16233	527
SCGB1D2	MUCL1	Q96DR8	482
SCGB1D2	PASD1	Q8IV76	449
SCGB1D2	MS4A12	Q9NXJ0	443
SCGB1D2	MUC13	Q9H3R2	427
SCGB1D2	ADCY10	Q96PN6	424
SCGB1D2	TSPAN8	P19075	418
SCGB1D2	APOL6	Q9BWW8	418
SCGB1D2	LIAS	O43766	417
SCGB1D2	SCGB1C1	Q8TD33	408

IntAct

20 interactions, top by confidence:

A	B	Type	Score
PPP2R2D	YEATS4	psi-mi:“MI:0914”(association)	0.730
DDX31	IGLL5	psi-mi:“MI:0914”(association)	0.530
RIBC1	CNOT1	psi-mi:“MI:0914”(association)	0.530
PER3	PER1	psi-mi:“MI:0914”(association)	0.500
CFAP119	SCGB1D2	psi-mi:“MI:0915”(physical association)	0.400
ALPK1	SCGB1D2	psi-mi:“MI:0915”(physical association)	0.400
SCGB1D2	COL14A1	psi-mi:“MI:0915”(physical association)	0.400
IFNA7	SCGB1D2	psi-mi:“MI:0915”(physical association)	0.400
RORC	ANKHD1	psi-mi:“MI:0914”(association)	0.350
GK	SCGB1D2	psi-mi:“MI:0914”(association)	0.350
LIN37	SCGB1D2	psi-mi:“MI:0914”(association)	0.350
SCGB1D2	COL14A1	psi-mi:“MI:0914”(association)	0.350
ITLN2	IGLC7	psi-mi:“MI:0914”(association)	0.350
TRAF3IP3	RGPD8	psi-mi:“MI:0914”(association)	0.350
MYCT1	SPTLC2	psi-mi:“MI:0914”(association)	0.350
GAREM1	SCGB1D2	psi-mi:“MI:0914”(association)	0.350
PRG3	IGLL5	psi-mi:“MI:0914”(association)	0.350
INSR	BLTP3B	psi-mi:“MI:0914”(association)	0.350

BioGRID (21): SCGB1D2 (Affinity Capture-MS), SCGB1D2 (Affinity Capture-MS), SCGB1D2 (Affinity Capture-MS), SCGB1D2 (Affinity Capture-MS), COL14A1 (Affinity Capture-MS), SCGB1D2 (Affinity Capture-MS), SCGB1D2 (Affinity Capture-MS), FSTL1 (Affinity Capture-MS), TMEM259 (Affinity Capture-MS), SCGB1D2 (Affinity Capture-MS), COL14A1 (Affinity Capture-MS), SCGB1D2 (Affinity Capture-MS), SCGB1D2 (Affinity Capture-MS), SCGB1D2 (Affinity Capture-MS), SCGB1D2 (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: A0JNP2, O95968, O95969, P02781, P02782, Q6XE38, P06913, P11684, P02779, P17559, Q06318, Q2VPS3, Q65C83, Q8MKG2, Q8VD96, Q9TS45

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

174 predictions. Top by Δscore:

Variant	Effect	Δscore
11:62242361:GG:G	donor_gain	1.0000
11:62242362:GG:G	donor_gain	1.0000
11:62242363:G:GG	donor_gain	1.0000
11:62243281:T:TA	acceptor_gain	1.0000
11:62243284:T:A	acceptor_gain	1.0000
11:62243286:CA:C	acceptor_loss	1.0000
11:62243287:A:AC	acceptor_loss	1.0000
11:62243287:A:AG	acceptor_gain	1.0000
11:62243288:G:GT	acceptor_gain	1.0000
11:62243288:GCC:G	acceptor_gain	1.0000
11:62243288:GCCA:G	acceptor_gain	1.0000
11:62243468:G:GT	donor_gain	1.0000
11:62243468:G:T	donor_gain	1.0000
11:62242358:CCAGG:C	donor_gain	0.9900
11:62242359:CAGG:C	donor_gain	0.9900
11:62242360:AGG:A	donor_gain	0.9900
11:62242361:GGG:G	donor_gain	0.9900
11:62242361:GGGT:G	donor_loss	0.9900
11:62242362:GGTG:G	donor_loss	0.9900
11:62242363:G:A	donor_loss	0.9900
11:62242364:T:G	donor_loss	0.9900
11:62243288:GC:G	acceptor_gain	0.9900
11:62243288:GCCAA:G	acceptor_gain	0.9900
11:62243454:G:GT	donor_gain	0.9900
11:62242365:GAG:G	donor_loss	0.9800
11:62243363:T:G	donor_gain	0.9800
11:62243472:TCCTG:T	donor_loss	0.9800
11:62243473:CCTG:C	donor_loss	0.9800
11:62243475:TGGT:T	donor_loss	0.9800
11:62243476:GG:G	donor_loss	0.9800

AlphaMissense

577 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:62243422:G:C	K63N	0.945
11:62243422:G:T	K63N	0.945
11:62243421:A:C	K63T	0.846
11:62243378:T:C	F49L	0.830
11:62243380:T:A	F49L	0.830
11:62243380:T:G	F49L	0.830
11:62243420:A:G	K63E	0.785
11:62243405:G:C	A58P	0.745
11:62243421:A:T	K63M	0.732
11:62243333:T:C	F34L	0.686
11:62243335:C:A	F34L	0.686
11:62243335:C:G	F34L	0.686
11:62243370:T:C	L46P	0.660
11:62243370:T:A	L46H	0.649
11:62243454:G:C	R74P	0.648
11:62243420:A:C	K63Q	0.647
11:62243305:C:G	C24W	0.641
11:62242336:T:A	V10D	0.640
11:62242345:C:A	A13D	0.637
11:62243303:T:C	C24R	0.622
11:62243432:G:C	D67H	0.622
11:62243439:T:G	M69R	0.607
11:62243358:T:C	F42S	0.599
11:62243325:T:C	L31P	0.597
11:62243379:T:G	F49C	0.592
11:62243396:G:C	A55P	0.587
11:62243385:C:A	A51D	0.584
11:62243357:T:C	F42L	0.583
11:62243359:C:A	F42L	0.583
11:62243359:C:G	F42L	0.583

dbSNP variants (sampled 300 via entrez): RS1000128297 (11:62240772 C>T), RS1001699064 (11:62240821 G>C), RS1001812185 (11:62240963 C>A,G,T), RS1003112168 (11:62241964 T>C), RS1003410869 (11:62243021 G>A,C), RS1003930569 (11:62241062 G>A), RS1004623826 (11:62245110 G>A), RS1005053258 (11:62241289 T>C), RS1005063156 (11:62240969 T>C), RS1005920408 (11:62244471 G>T), RS1006055731 (11:62242646 G>C), RS1006508366 (11:62241619 C>A,T), RS1006886994 (11:62244230 C>T), RS1007279639 (11:62244914 A>G), RS1007509755 (11:62242934 T>C)

Disease associations

OMIM: gene MIM:615061 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 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
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

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects cotreatment, increases expression	3
Aflatoxin B1	affects expression, decreases expression, increases expression	3
Benzo(a)pyrene	decreases expression, affects methylation	2
Nickel	decreases expression	2
Progesterone	increases expression, affects cotreatment	2
propionaldehyde	increases expression	1
o,p’-DDT	increases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	increases expression	1
pentanal	increases expression	1
nutlin 3	affects cotreatment, increases expression	1
3-hydroxy-4-prenyl-5-methoxystilbene-2-carboxylic acid	decreases expression	1
Zoledronic Acid	increases expression	1
Arsenic Trioxide	increases expression	1
Acetaminophen	decreases expression	1
Aldehydes	increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Ethinyl Estradiol	increases expression	1
Formaldehyde	increases expression	1
Lead	affects expression	1
Methyl Methanesulfonate	increases expression	1
Tretinoin	decreases expression	1
Cyclosporine	decreases expression	1

Clinical trials (associated diseases)

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