SERTAD3

Summary

SERTAD3 (SERTA domain containing 3, HGNC:17931) is a protein-coding gene on chromosome 19q13.2, encoding SERTA domain-containing protein 3 (Q9UJW9). Antiviral interferon-stimulated protein that plays a role in innate immunity and in the suppression of viruses through different mechanisms.

The protein encoded by this gene was identified in a yeast two-hybrid assay employing the second subunit of human replication protein A as bait. It is localized to the nucleus and its expression is significantly higher in cancer cell lines compared to normal cell lines. This protein has also been shown to be a strong transcriptional co-activator. Alternative splicing has been observed at this locus and two variants, both encoding the same protein, have been identified.

Source: NCBI Gene 29946 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 37 total
• MANE Select transcript: NM_203344

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17931
Approved symbol	SERTAD3
Name	SERTA domain containing 3
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	RBT1
Ensembl gene	ENSG00000167565
Ensembl biotype	protein_coding
OMIM	612125
Entrez	29946

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 27 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000322354, ENST00000392028, ENST00000596456, ENST00000599706, ENST00000601217, ENST00000865349, ENST00000865350, ENST00000865351, ENST00000865352, ENST00000865353, ENST00000865354, ENST00000865355, ENST00000865356, ENST00000865357, ENST00000921116, ENST00000921117, ENST00000921118, ENST00000921119, ENST00000921120, ENST00000921121, ENST00000921122, ENST00000921123, ENST00000921124, ENST00000921125, ENST00000921126, ENST00000921127, ENST00000946968, ENST00000946969

RefSeq mRNA: 2 — MANE Select: NM_203344 NM_013368, NM_203344

CCDS: CCDS12558

Canonical transcript exons

ENST00000322354 — 2 exons

Exon	Start	End
ENSE00003162767	40444215	40444335
ENSE00004282584	40440844	40442086

Expression profiles

Bgee: expression breadth ubiquitous, 232 present calls, max score 96.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.9307 / max 215.7627, expressed in 1815 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
180991	27.5967	1815
180990	0.3341	178

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	96.36	gold quality
secondary oocyte	CL:0000655	94.99	gold quality
mucosa of stomach	UBERON:0001199	94.61	gold quality
monocyte	CL:0000576	93.91	gold quality
mononuclear cell	CL:0000842	93.44	gold quality
leukocyte	CL:0000738	93.23	gold quality
lower esophagus mucosa	UBERON:0035834	92.90	gold quality
left uterine tube	UBERON:0001303	92.57	gold quality
tibial artery	UBERON:0007610	92.21	gold quality
popliteal artery	UBERON:0002250	92.20	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.85	gold quality
muscle layer of sigmoid colon	UBERON:0035805	91.77	gold quality
lower esophagus	UBERON:0013473	91.65	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.65	gold quality
omental fat pad	UBERON:0010414	91.60	gold quality
peritoneum	UBERON:0002358	91.55	gold quality
aorta	UBERON:0000947	91.03	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.89	gold quality
apex of heart	UBERON:0002098	90.76	gold quality
mucosa of transverse colon	UBERON:0004991	90.70	gold quality
granulocyte	CL:0000094	90.44	gold quality
right coronary artery	UBERON:0001625	90.43	gold quality
gall bladder	UBERON:0002110	90.40	gold quality
adipose tissue of abdominal region	UBERON:0007808	90.40	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.38	gold quality
body of stomach	UBERON:0001161	90.22	gold quality
transverse colon	UBERON:0001157	90.21	gold quality
right atrium auricular region	UBERON:0006631	90.03	gold quality
left coronary artery	UBERON:0001626	89.85	gold quality
thoracic aorta	UBERON:0001515	89.70	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-7052	yes	136.67
E-ANND-3	yes	7.36

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

42 targeting SERTAD3, 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-8485	100.00	77.57	4731
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-141-5P	99.57	67.86	897
HSA-MIR-6833-5P	99.50	68.93	1161
HSA-MIR-12117	99.50	67.57	868
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-4696	99.48	67.48	1040
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-4695-5P	99.06	64.87	1151
HSA-MIR-4752	98.71	68.04	833

Literature-anchored findings (GeneRIF, showing 2)

• Transduction of stably expressed human SERTAD3 induces cell transformation in vitro and tumor formation in mice via a transcription factor E2F-dependent mechanism. (PMID:17260023)
• Type-IInterferon-Inducible SERTAD3 Inhibits Influenza A Virus Replication by Blocking the Assembly of Viral RNA Polymerase Complex. (PMID:33147462)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Sertad3	ENSMUSG00000055200
rattus_norvegicus	Sertad3	ENSRNOG00000037690

Paralogs (1): SERTAD1 (ENSG00000197019)

Protein

Protein identifiers

SERTA domain-containing protein 3 — Q9UJW9 (reviewed: Q9UJW9)

Alternative names: Replication protein-binding trans-activator

All UniProt accessions (3): Q9UJW9, M0QXL4, M0R352

UniProt curated annotations — full annotation on UniProt →

Function. Antiviral interferon-stimulated protein that plays a role in innate immunity and in the suppression of viruses through different mechanisms. Plays a role in the late phase response of TLR-induced immune effector expression. During influenza infection, interacts with PB2, PB1, and PA to disrupt the formation of the viral RdRp complex. Inhibits zika virus by interacting with the capsid protein in the nucleolus and reducing its abundance through proteasomal degradation. Strong transcriptional coactivator.

Subunit / interactions. Interacts with RPA2. (Microbial infection) Interacts with influenza virus PA, PB1 and PB2,leading to inhibition of RdRp complex assembly. (Microbial infection) Interacts with zika virus capsid protein.

Subcellular location. Nucleus.

RefSeq proteins (2): NP_037500, NP_976219* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009263	SERTA_dom	Domain
IPR039585	SERTAD3	Family

Pfam: PF06031

UniProt features (5 total): region of interest 2, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UJW9-F1	67.09	0.18

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 153 (showing top): GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_GROWTH, IVANOVA_HEMATOPOIESIS_MATURE_CELL, NAGASHIMA_NRG1_SIGNALING_UP, FOSTER_TOLERANT_MACROPHAGE_UP, BLALOCK_ALZHEIMERS_DISEASE_UP, FISCHER_G2_M_CELL_CYCLE, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, LYF1_01, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_UP, CREB_Q3, FISCHER_DREAM_TARGETS, AMIT_SERUM_RESPONSE_120_MCF10A, TGCCTTA_MIR124A

GO Biological Process (3): regulation of DNA-templated transcription (GO:0006355), negative regulation of cell growth (GO:0030308), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	2
regulation of gene expression	1
regulation of RNA biosynthetic process	1
regulation of cell growth	1
cell growth	1
negative regulation of growth	1
negative regulation of cellular process	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

422 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SERTAD3	RPA2	P15927	822
SERTAD3	STN1	Q9H668	783
SERTAD3	SERTAD4	Q9NUC0	643
SERTAD3	SERTAD2	Q14140	629
SERTAD3	TMEM50A	O95807	580
SERTAD3	CCNA1	P78396	493
SERTAD3	CDCA4	Q9BXL8	484
SERTAD3	CCNA2	P20248	476
SERTAD3	MRPS18A	Q9NVS2	468
SERTAD3	NPEPPS	P55786	450
SERTAD3	INPP5A	Q14642	443
SERTAD3	SLC22A16	Q86VW1	443
SERTAD3	BID	P55957	441
SERTAD3	RNLS	Q5VYX0	441
SERTAD3	E2F1	Q01094	423

IntAct

194 interactions, top by confidence:

A	B	Type	Score
SERTAD3	USHBP1	psi-mi:“MI:0915”(physical association)	0.790
USHBP1	SERTAD3	psi-mi:“MI:0915”(physical association)	0.790
KPNA2	SERTAD3	psi-mi:“MI:0915”(physical association)	0.670
SERTAD3	KPNA2	psi-mi:“MI:0915”(physical association)	0.670
UBL5	SERTAD3	psi-mi:“MI:0915”(physical association)	0.600
SNRPB	SERTAD3	psi-mi:“MI:0915”(physical association)	0.600
SERTAD3	SNRPB	psi-mi:“MI:0915”(physical association)	0.600
SERTAD3	UBL5	psi-mi:“MI:0915”(physical association)	0.600
RPA2	SERTAD3	psi-mi:“MI:0915”(physical association)	0.600
SERTAD3	RPA2	psi-mi:“MI:0915”(physical association)	0.600
SERTAD3	RPA2	psi-mi:“MI:0403”(colocalization)	0.600
SPG11	SERTAD3	psi-mi:“MI:0915”(physical association)	0.560
FBXO44	SERTAD3	psi-mi:“MI:0915”(physical association)	0.560
SERTAD3	SPG11	psi-mi:“MI:0915”(physical association)	0.560
SERTAD3	FBXO44	psi-mi:“MI:0915”(physical association)	0.560
BRL1	SERTAD3	psi-mi:“MI:0915”(physical association)	0.560
	SERTAD3	psi-mi:“MI:0915”(physical association)	0.560
SERTAD3	RPC11	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (54): SERTAD3 (Two-hybrid), SPG11 (Two-hybrid), FBXO44 (Two-hybrid), USHBP1 (Two-hybrid), USHBP1 (Affinity Capture-Western), SERTAD3 (Two-hybrid), SERTAD3 (Two-hybrid), SERTAD3 (Two-hybrid), SERTAD3 (Two-hybrid), SERTAD3 (Two-hybrid), SERTAD3 (Two-hybrid), SERTAD3 (Two-hybrid), SERTAD3 (Two-hybrid), SERTAD3 (Two-hybrid), SERTAD3 (Two-hybrid)

ESM2 similar proteins: A2RU30, D3YN49, D3ZDX9, D6RGH6, E9PV82, F1QN48, F1SLM8, F7BHS0, G3N1S4, H2M146, O35451, O94983, P10166, P12524, P12525, P20389, P23999, Q08B36, Q14140, Q14153, Q1HGE8, Q3UZ45, Q5JXC2, Q5M9G5, Q5R815, Q61817, Q64210, Q68DK7, Q6NSI3, Q6P1D7, Q6PB51, Q6PDM1, Q7TNY7, Q80Y50, Q8BP99, Q8BXQ8, Q8IY92, Q8K3I4, Q8K589, Q8R0W1

Diamond homologs: Q9ERC3, Q9JL10, Q9UHV2, Q9UJW9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

116 predictions. Top by Δscore:

Variant	Effect	Δscore
19:40442321:A:AC	donor_gain	0.9800
19:40442322:C:CC	donor_gain	0.9800
19:40442083:TGCC:T	acceptor_gain	0.9700
19:40442084:GCCCT:G	acceptor_loss	0.9700
19:40442086:CCT:C	acceptor_loss	0.9700
19:40442087:C:CG	acceptor_loss	0.9700
19:40442088:T:G	acceptor_loss	0.9700
19:40442085:CC:C	acceptor_gain	0.9600
19:40442086:CC:C	acceptor_gain	0.9600
19:40442087:C:CC	acceptor_gain	0.9600
19:40442322:CTTG:C	donor_gain	0.9600
19:40442317:A:AC	donor_gain	0.9300
19:40442318:C:CC	donor_gain	0.9300
19:40442542:G:C	donor_gain	0.9300
19:40442318:CTTA:C	donor_gain	0.9100
19:40442319:TTA:T	donor_loss	0.9100
19:40442320:TACTT:T	donor_loss	0.9100
19:40442089:G:GC	acceptor_gain	0.9000
19:40442317:ACTT:A	donor_loss	0.9000
19:40442084:GCC:G	acceptor_gain	0.8700
19:40442085:CCC:C	acceptor_gain	0.8700
19:40442402:AAGTT:A	donor_gain	0.8400
19:40442356:T:TA	donor_gain	0.8000
19:40442378:T:C	donor_gain	0.7900
19:40442486:G:T	donor_gain	0.7800
19:40442082:ATGCC:A	acceptor_gain	0.7600
19:40441918:G:A	donor_gain	0.7300
19:40442089:G:C	acceptor_gain	0.7300
19:40442313:T:TA	donor_gain	0.7300
19:40442322:CT:C	donor_gain	0.7200

AlphaMissense

1270 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:40441911:A:G	L57P	0.994
19:40441914:A:T	V56D	0.993
19:40442060:C:A	R7S	0.993
19:40442060:C:G	R7S	0.993
19:40442063:C:A	K6N	0.993
19:40442063:C:G	K6N	0.993
19:40441911:A:T	L57H	0.988
19:40441962:T:A	K40I	0.988
19:40441511:C:A	M190I	0.987
19:40441511:C:G	M190I	0.987
19:40441511:C:T	M190I	0.987
19:40441515:A:T	I189N	0.987
19:40441908:A:T	I58N	0.987
19:40441961:T:A	K40N	0.987
19:40441961:T:G	K40N	0.987
19:40442061:C:A	R7M	0.987
19:40441503:A:T	I193N	0.986
19:40441797:A:T	I95N	0.986
19:40442061:C:G	R7T	0.986
19:40441515:A:C	I189S	0.985
19:40441896:A:G	L62P	0.985
19:40441908:A:G	I58T	0.985
19:40441901:G:C	N60K	0.984
19:40441901:G:T	N60K	0.984
19:40441908:A:C	I58S	0.983
19:40441902:T:A	N60I	0.981
19:40441920:C:A	R54M	0.981
19:40441971:G:A	S37F	0.981
19:40441515:A:G	I189T	0.980
19:40441788:A:G	I98T	0.980

dbSNP variants (sampled 300 via entrez): RS1000655884 (19:40441149 GCTTT>G), RS1000760729 (19:40446330 C>T), RS1001386106 (19:40444780 C>G,T), RS1001534190 (19:40442124 C>A,T), RS1001560658 (19:40441832 G>A), RS1001880290 (19:40442423 C>G), RS1001924798 (19:40446116 G>A), RS1002019758 (19:40445845 G>A), RS1002269808 (19:40440859 T>C), RS1002944000 (19:40443317 A>C), RS1003822135 (19:40443572 G>A), RS1004352944 (19:40443370 G>A), RS1004785570 (19:40441840 G>C), RS1005143829 (19:40442078 C>T), RS1005343902 (19:40444409 G>A)

Disease associations

OMIM: gene MIM:612125 | 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
GCST003827_4	Otitis media	2.000000e-07
GCST003828_1	Otitis media (chronic)	3.000000e-08
GCST003829_4	Otitis media (recurrent)	1.000000e-07
GCST90002396_39	Mean reticulocyte volume	1.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010701	mean reticulocyte volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

32 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
potassium chromate(VI)	decreases expression, affects cotreatment	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
bisphenol F	affects cotreatment, increases expression	1
alpha phellandrene	increases expression	1
triphenyl phosphate	affects expression	1
arsenite	affects binding, increases reaction	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
abrine	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression	1
jinfukang	decreases expression, increases reaction	1
(+)-JQ1 compound	decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
Leflunomide	decreases expression	1
Acetaminophen	increases expression	1
Amiodarone	increases expression	1
Benzo(a)pyrene	increases methylation, decreases methylation	1
Cisplatin	decreases expression, increases reaction	1
Dexamethasone	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
Vincristine	decreases expression	1
Zinc	affects cotreatment, increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Cadmium Chloride	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2F2	Abcam HeLa SERTAD3 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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