SCGB1D4

Summary

SCGB1D4 (secretoglobin family 1D member 4, HGNC:31748) is a protein-coding gene on chromosome 11q12.3, encoding Secretoglobin family 1D member 4 (Q6XE38). Seems to be involved in the regulation of chemotactic cell migration and invasion.

Predicted to be located in extracellular region. Predicted to be active in extracellular space.

Source: NCBI Gene 404552 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 12 total
• MANE Select transcript: NM_206998

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31748
Approved symbol	SCGB1D4
Name	secretoglobin family 1D member 4
Location	11q12.3
Locus type	gene with protein product
Status	Approved
Aliases	IIS
Ensembl gene	ENSG00000197745
Ensembl biotype	protein_coding
OMIM	615062
Entrez	404552

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000358585

RefSeq mRNA: 1 — MANE Select: NM_206998 NM_206998

CCDS: CCDS31583

Canonical transcript exons

ENST00000358585 — 3 exons

Exon	Start	End
ENSE00001399614	62297472	62297658
ENSE00001426884	62298956	62299075
ENSE00001641306	62296281	62296419

Expression profiles

Bgee: expression breadth broad, 44 present calls, max score 99.52.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0239 / max 19.6752, expressed in 5 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
120091	0.0239	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	99.52	gold quality
endometrium	UBERON:0001295	84.25	gold quality
fallopian tube	UBERON:0003889	80.44	gold quality
left uterine tube	UBERON:0001303	78.56	gold quality
endocervix	UBERON:0000458	61.26	gold quality
right testis	UBERON:0004534	48.62	gold quality
left testis	UBERON:0004533	47.18	gold quality
testis	UBERON:0000473	46.91	gold quality
uterine cervix	UBERON:0000002	38.29	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	35.45	gold quality
bone marrow	UBERON:0002371	35.29	silver quality
body of uterus	UBERON:0009853	34.37	gold quality
myometrium	UBERON:0001296	33.54	gold quality
muscle tissue	UBERON:0002385	32.58	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
right coronary artery	UBERON:0001625	32.00	silver quality
sural nerve	UBERON:0015488	30.93	gold quality
prefrontal cortex	UBERON:0000451	30.56	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
primary visual cortex	UBERON:0002436	29.34	silver quality
liver	UBERON:0002107	28.87	gold quality
placenta	UBERON:0001987	28.79	gold quality
islet of Langerhans	UBERON:0000006	28.30	gold quality
duodenum	UBERON:0002114	28.14	gold quality
lymph node	UBERON:0000029	27.57	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

9 targeting SCGB1D4, 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-9-3P	99.96	70.88	2068
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-548U	99.65	67.78	1463
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-122B-5P	99.46	70.81	1457
HSA-MIR-3606-5P	99.31	69.67	1168
HSA-MIR-3978	99.24	68.39	2201

Literature-anchored findings (GeneRIF, showing 2)

• This interferon-gamma-inducible secretoglobin gene, SCGB1D4, is expressed in virtually all tissues, and the highest level of expression is detectable in lymph nodes, tonsil, cultured lymphoblasts, and the ovary. (PMID:15034037)
• Studied three single nucleotide polymorphisms (SNPs) in SCGB1D4 (secretoglobin family 1D member 4) . Found the SNPs to be associated with an increased risk of adenoid hypertrophy, as well as asthma, allergy, sleep-disordered breathing. (PMID:28263490)

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): SCGB1D2 (ENSG00000124935), SCGB1D1 (ENSG00000168515)

Protein

Protein identifiers

Secretoglobin family 1D member 4 — Q6XE38 (reviewed: Q6XE38)

Alternative names: IFN-gamma-inducible secretoglobin

All UniProt accessions (1): Q6XE38

UniProt curated annotations — full annotation on UniProt →

Function. Seems to be involved in the regulation of chemotactic cell migration and invasion.

Subcellular location. Secreted.

Tissue specificity. Expressed in all tissues; the highest level of expression is detectable in lymph nodes, tonsil, cultured lymphoblasts and ovary.

Induction. By IFNG/IFN-gamma.

Similarity. Belongs to the secretoglobin family. Lipophilin subfamily.

RefSeq proteins (1): NP_996881* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016126	Secretoglobin	Family
IPR035960	Secretoglobin_sf	Homologous_superfamily

Pfam: PF01099

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

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6XE38-F1	87.72	0.57

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 5 (showing top): KUMAR_PATHOGEN_LOAD_BY_MACROPHAGES, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, chr11q12, GSE32034_UNTREATED_VS_ROSIGLIZATONE_TREATED_LY6C_LOW_MONOCYTE_UP, GSE20727_ROS_INH_VS_ROS_INH_AND_DNFB_ALLERGEN_TREATED_DC_DN

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

284 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SCGB1D4	TLE7	A0A1W2PR48	626
SCGB1D4	PPP4R3C	Q6ZMV5	570
SCGB1D4	IGF1	P01343	526
SCGB1D4	METTL27	Q8N6F8	493
SCGB1D4	GET3	O43681	485
SCGB1D4	PPP4R3A	Q6IN85	479
SCGB1D4	INS	P01308	477
SCGB1D4	PPP4R3B	Q5MIZ7	447
SCGB1D4	NTSR2	O95665	408
SCGB1D4	SCGB1C1	Q8TD33	407
SCGB1D4	AKT1	P31749	394
SCGB1D4	SCGB2A1	O75556	372
SCGB1D4	RPS6KB2	Q9UBS0	370
SCGB1D4	SGK1	O00141	370
SCGB1D4	NKRF	O15226	365

IntAct

3 interactions, top by confidence:

A	B	Type	Score
SCGB1D4	EGFR	psi-mi:“MI:0914”(association)	0.530

BioGRID (46): PRUNE (Affinity Capture-MS), NAALAD2 (Affinity Capture-MS), CNTNAP3 (Affinity Capture-MS), CACNA2D1 (Affinity Capture-MS), ADAM9 (Affinity Capture-MS), GPR98 (Affinity Capture-MS), BACE1 (Affinity Capture-MS), CACNA2D2 (Affinity Capture-MS), CNNM1 (Affinity Capture-MS), LNPEP (Affinity Capture-MS), BCHE (Affinity Capture-MS), CD109 (Affinity Capture-MS), COL6A2 (Affinity Capture-MS), ITGA8 (Affinity Capture-MS), ARSK (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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	10
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

202 predictions. Top by Δscore:

Variant	Effect	Δscore
11:62297532:T:TA	donor_gain	1.0000
11:62296419:CCTG:C	acceptor_loss	0.9900
11:62296420:C:A	acceptor_loss	0.9900
11:62296421:T:C	acceptor_loss	0.9900
11:62297532:TCCA:T	donor_gain	0.9900
11:62297655:TGGG:T	acceptor_gain	0.9900
11:62297659:C:CC	acceptor_gain	0.9900
11:62297665:C:CT	acceptor_gain	0.9900
11:62298954:AC:A	donor_gain	0.9900
11:62298955:CC:C	donor_gain	0.9900
11:62296427:C:CT	acceptor_gain	0.9800
11:62296428:A:T	acceptor_gain	0.9800
11:62297527:TC:T	donor_gain	0.9800
11:62297668:A:T	acceptor_gain	0.9800
11:62298950:ACTC:A	donor_loss	0.9800
11:62298951:CTCA:C	donor_loss	0.9800
11:62298952:TCAC:T	donor_loss	0.9800
11:62298953:CACC:C	donor_loss	0.9800
11:62298954:A:AC	donor_gain	0.9800
11:62298954:A:AG	donor_loss	0.9800
11:62298955:C:CC	donor_gain	0.9800
11:62298955:C:CT	donor_loss	0.9800
11:62296420:C:CC	acceptor_gain	0.9700
11:62297602:T:C	acceptor_gain	0.9700
11:62297656:GGG:G	acceptor_gain	0.9700
11:62297658:GCTG:G	acceptor_loss	0.9700
11:62297659:C:G	acceptor_loss	0.9700
11:62297660:T:A	acceptor_loss	0.9700
11:62297667:C:CT	acceptor_gain	0.9700
11:62298948:GTACT:G	donor_loss	0.9700

AlphaMissense

527 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:62297525:C:A	K63N	0.874
11:62297525:C:G	K63N	0.874
11:62297612:G:C	F34L	0.844
11:62297612:G:T	F34L	0.844
11:62297614:A:G	F34L	0.844
11:62297526:T:G	K63T	0.702
11:62297527:T:C	K63E	0.688
11:62297542:C:G	A58P	0.686
11:62297606:G:C	F36L	0.673
11:62297606:G:T	F36L	0.673
11:62297608:A:G	F36L	0.673
11:62297526:T:A	K63M	0.652
11:62297508:A:G	I69T	0.640
11:62297644:A:G	C24R	0.623
11:62297634:A:T	V27D	0.613
11:62297519:G:C	C65W	0.593
11:62298995:A:G	C6R	0.574

dbSNP variants (sampled 300 via entrez): RS1000450885 (11:62299529 GA>G), RS1000592393 (11:62297411 T>C,G), RS1001171455 (11:62297826 A>G), RS1001271993 (11:62299122 G>C), RS1002096912 (11:62297754 T>C,G), RS1002299259 (11:62298136 C>G), RS1002846426 (11:62297109 C>T), RS1002941314 (11:62297321 C>T), RS1003280103 (11:62296026 G>A), RS1004299842 (11:62299953 C>T), RS1004877749 (11:62296969 G>C), RS1005472240 (11:62298204 A>G), RS1006443587 (11:62300238 T>A,C), RS1006748846 (11:62299459 C>T), RS1006809827 (11:62297066 G>A)

Disease associations

OMIM: gene MIM:615062 | 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
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
GCST011065_7	Levodopa-induced dyskinesia in levodopa treated Parkinson’s disease	3.000000e-06
GCST90020025_936	Waist-to-hip ratio adjusted for BMI	2.000000e-08
GCST90020027_1461	Waist-hip index	9.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0006319	HIV viral set point measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0010747	response to levodopa

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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