SCAND3

Summary

SCAND3 (SCAN domain containing 3, HGNC:13851) is a protein-coding gene on chromosome 6p22.1, encoding SCAN domain-containing protein 3 (Q6R2W3).

Predicted to enable nucleic acid binding activity. Involved in positive regulation of cell cycle and positive regulation of epithelial cell proliferation. Located in cytoplasm.

Source: NCBI Gene 114821 — RefSeq curated summary.

At a glance

• GWAS associations: 30
• Clinical variants (ClinVar): 84 total
• MANE Select transcript: NM_052923

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13851
Approved symbol	SCAND3
Name	SCAN domain containing 3
Location	6p22.1
Locus type	gene with protein product
Status	Approved
Aliases	ZFP38-L, KIAA1925, FLJ31087, Buster4, FAM200D
Ensembl gene	ENSG00000232040
Ensembl biotype	protein_coding
OMIM	615254
Entrez	114821

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000452236, ENST00000524745, ENST00000526291, ENST00000530247, ENST00000646382, ENST00000927696

RefSeq mRNA: 2 — MANE Select: NM_052923 NM_001329616, NM_052923

CCDS: CCDS34355, CCDS87376

Canonical transcript exons

ENST00000452236 — 4 exons

Exon	Start	End
ENSE00002439661	28574644	28576136
ENSE00002480261	28586298	28587298
ENSE00003522808	28579272	28579419
ENSE00003821209	28570535	28573827

Expression profiles

Bgee: expression breadth ubiquitous, 170 present calls, max score 81.69.

FANTOM5 (CAGE): breadth broad, TPM avg 2.1797 / max 34.4213, expressed in 783 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
72426	1.8098	730
72429	0.1276	42
72428	0.0868	35
72427	0.0761	35
72425	0.0568	21
72430	0.0226	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.69	gold quality
left testis	UBERON:0004533	80.00	gold quality
testis	UBERON:0000473	79.93	gold quality
right testis	UBERON:0004534	79.39	gold quality
secondary oocyte	CL:0000655	79.28	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.54	gold quality
ganglionic eminence	UBERON:0004023	75.98	gold quality
corpus epididymis	UBERON:0004359	74.96	gold quality
cortical plate	UBERON:0005343	74.86	gold quality
ventricular zone	UBERON:0003053	73.92	gold quality
adrenal tissue	UBERON:0018303	73.48	gold quality
oocyte	CL:0000023	73.05	gold quality
islet of Langerhans	UBERON:0000006	70.75	gold quality
sperm	CL:0000019	70.42	gold quality
sural nerve	UBERON:0015488	70.32	gold quality
cerebellar hemisphere	UBERON:0002245	67.67	gold quality
cerebellar cortex	UBERON:0002129	67.56	gold quality
cerebellum	UBERON:0002037	66.99	gold quality
right hemisphere of cerebellum	UBERON:0014890	66.90	gold quality
seminal vesicle	UBERON:0000998	65.56	gold quality
caput epididymis	UBERON:0004358	64.22	gold quality
prefrontal cortex	UBERON:0000451	63.97	gold quality
rectum	UBERON:0001052	62.85	gold quality
pancreas	UBERON:0001264	62.75	gold quality
tibialis anterior	UBERON:0001385	61.86	silver quality
right lobe of liver	UBERON:0001114	61.79	gold quality
ileal mucosa	UBERON:0000331	61.43	silver quality
pigmented layer of retina	UBERON:0001782	61.29	gold quality
right adrenal gland cortex	UBERON:0035827	60.63	gold quality
right adrenal gland	UBERON:0001233	60.59	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.34

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA2542.1	SCAND3	BED zinc finger factors

JASPAR matrix evidence (PMIDs): PMID:39605530

miRNA regulators (miRDB)

15 targeting SCAND3, 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-3148	99.97	75.06	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-1-5P	98.70	68.66	1017
HSA-MIR-4305	97.94	68.63	533
HSA-MIR-1295B-3P	96.68	66.11	276
HSA-MIR-4524B-3P	95.52	64.12	964

Literature-anchored findings (GeneRIF, showing 3)

• the present study indicated that ZNF452 may be an upstream regulator of AKT-GSK3beta signaling pathway and facilitates proliferation and invasion of non-small cell lung cancer (PMID:28418919)
• Genome-wide association study on blood pressure traits in the Iranian population suggests ZBED9 as a new locus for hypertension. (PMID:34083597)
• The AGT epistasis pattern proposed a novel role for ZBED9 in regulating blood pressure: Tehran Cardiometabolic genetic study (TCGS). (PMID:35577038)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zbed5	ENSMUSG00000034173
rattus_norvegicus	Zbed5	ENSRNOG00000000918

Paralogs (18): GTF2IRD1 (ENSG00000006704), ZMYM2 (ENSG00000121741), ZMYM5 (ENSG00000132950), THAP12 (ENSG00000137492), ZMYM4 (ENSG00000146463), ZMYM3 (ENSG00000147130), ZMYM6 (ENSG00000163867), KIAA1958 (ENSG00000165185), GTF2IRD2B (ENSG00000174428), EPM2AIP1 (ENSG00000178567), GTF2IRD2 (ENSG00000196275), ZMYM1 (ENSG00000197056), QRICH1 (ENSG00000198218), FAM200C (ENSG00000221886), FAM200A (ENSG00000221909), ZBED5 (ENSG00000236287), FAM200B (ENSG00000237765), GTF2I (ENSG00000263001)

Protein

Protein identifiers

SCAN domain-containing protein 3 — Q6R2W3 (reviewed: Q6R2W3)

Alternative names: Transposon-derived Buster4 transposase-like protein, Zinc finger BED domain-containing protein 9

All UniProt accessions (3): A0A1U9X8W9, A0A2R8Y5N3, Q6R2W3

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus.

Tissue specificity. Weakly expressed in the lung (at protein level).

Miscellaneous. Highly expressed in non-small-cell lung carcinoma (NSCLC) tissue, with increased expression correlating with advanced disease, lymph node metastases and poor prognosis, as such may be a candidate prognostic marker. May act as an oncogene and promote tumor growth via positive regulation of cell cycle progression at G1/S phase transition. May promote invasion and metastasis via activation of the AKT/GSK-3 beta signaling pathway. Expressed in the cytoplasm in NSCLC tissue. May be derived from an ancient transposon that has lost its ability to translocate.

RefSeq proteins (2): NP_001316545, NP_443155* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001584	Integrase_cat-core	Domain
IPR003309	SCAN_dom	Domain
IPR012337	RNaseH-like_sf	Homologous_superfamily
IPR036397	RNaseH_sf	Homologous_superfamily
IPR038269	SCAN_sf	Homologous_superfamily
IPR057560	Znf_SCAND3	Domain

Pfam: PF02023, PF23663

UniProt features (13 total): sequence conflict 6, domain 2, coiled-coil region 2, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6R2W3-F1	72.39	0.28

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 55 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_DNA_INTEGRATION, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, MODULE_205, KOYAMA_SEMA3B_TARGETS_UP, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_EPITHELIAL_CELL_PROLIFERATION, GOBP_POSITIVE_REGULATION_OF_CELL_CYCLE, GOBP_DNA_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CELL_POPULATION_PROLIFERATION, HMG20B_TARGET_GENES, HOXA7_TARGET_GENES, KLF14_TARGET_GENES, PGBD5_TARGET_GENES, SKIL_TARGET_GENES

GO Biological Process (3): DNA integration (GO:0015074), positive regulation of cell cycle (GO:0045787), positive regulation of epithelial cell proliferation (GO:0050679)

GO Molecular Function (2): nucleic acid binding (GO:0003676), protein dimerization activity (GO:0046983)

GO Cellular Component (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA metabolic process	1
cell cycle	1
positive regulation of cellular process	1
regulation of cell cycle	1
positive regulation of cell population proliferation	1
epithelial cell proliferation	1
regulation of epithelial cell proliferation	1
binding	1
protein binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1172 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SCAND3	HYAL1	Q12794	417
SCAND3	TRIM69	Q86WT6	409
SCAND3	ZBED4	O75132	402
SCAND3	TMPRSS11D	O60235	393
SCAND3	GIN1	Q9NXP7	393
SCAND3	ANGPTL7	O43827	369
SCAND3	SGIP1	Q9BQI5	357
SCAND3	ZNF19	P17023	356
SCAND3	VSIG8	P0DPA2	353
SCAND3	ZBED10P	Q96FA7	348
SCAND3	SLC5A9	Q2M3M2	342
SCAND3	HID1	Q8IV36	338
SCAND3	NR2C2AP	Q86WQ0	332
SCAND3	PGCKA1	Q8IY42	321
SCAND3	ZBTB9	Q96C00	321

IntAct

19 interactions, top by confidence:

A	B	Type	Score
ZNF396	ZNF24	psi-mi:“MI:0914”(association)	0.700
ZSCAN32	ZNF197	psi-mi:“MI:0914”(association)	0.530
ZKSCAN4	ZNF213	psi-mi:“MI:0914”(association)	0.530
ZNF397	ZNF197	psi-mi:“MI:0914”(association)	0.530
ZNF396	ZNF24	psi-mi:“MI:0914”(association)	0.530
KPNA4	SCAND3	psi-mi:“MI:0915”(physical association)	0.400
KRBA2	SCAND3	psi-mi:“MI:0915”(physical association)	0.400
ZSCAN20	ZNF197	psi-mi:“MI:0914”(association)	0.350
ZNF232	ZNF197	psi-mi:“MI:0914”(association)	0.350
ZNF444	AHCYL1	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
ZSCAN23	ZNF263	psi-mi:“MI:0914”(association)	0.350
ZSCAN21	IPO8	psi-mi:“MI:0914”(association)	0.350

BioGRID (27): ZBED9 (Affinity Capture-MS), ZBED9 (Affinity Capture-MS), ZBED9 (Affinity Capture-MS), ZBED9 (Affinity Capture-MS), ZBED9 (Affinity Capture-MS), ZBED9 (Affinity Capture-MS), ZBED9 (Affinity Capture-MS), ZBED9 (Affinity Capture-MS), ZBED9 (Affinity Capture-MS), ZBED9 (Affinity Capture-MS), ZBED9 (Affinity Capture-MS), ZBED9 (Affinity Capture-RNA), ZBED9 (Affinity Capture-MS), ZBED9 (Affinity Capture-MS), ZBED9 (Affinity Capture-MS)

ESM2 similar proteins: A0A0B7P3V8, A4FUB7, A4H7G5, A4HVU6, A6NKG5, B4NSS9, B6EU02, F4I1N8, H2KZW3, O10318, O13329, P04586, P0C2J7, P18475, P34601, P47024, Q01577, Q05101, Q09178, Q09293, Q1L6Q1, Q3S4A7, Q4DCH3, Q4QFY1, Q4R6I1, Q52QI2, Q57X81, Q5RBK0, Q5RDX4, Q62120, Q66H30, Q6R2W3, Q7KLI1, Q7LHG5, Q8CDM1, Q8K259, Q8N157, Q90179, Q91829, Q99315

Diamond homologs: A1YEP8, A1YEQ3, A1YEV9, A1YFW2, A1YFW6, A1YG26, A1YG48, A1YG60, A1YGJ4, A1YGK6, A2T6E3, A2T6V8, A2T6W2, A2T712, A2T736, A2T7D2, A2T7D7, A2T7F2, A2T7F4, A2T7L7, A2T812, A6QNZ0, A6QPT6, B2KFW1, O14709, O14771, O14978, O15535, O43309, O60304, O95125, P10073, P17022, P17028, P17029, P17040, P28698, P49910, P51815, P59923

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	75
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

512 predictions. Top by Δscore:

Variant	Effect	Δscore
6:28579417:GACC:G	acceptor_loss	1.0000
6:28579420:C:CA	acceptor_loss	1.0000
6:28573834:T:C	acceptor_gain	0.9900
6:28573834:T:TC	acceptor_gain	0.9900
6:28576135:CC:C	acceptor_gain	0.9900
6:28576136:CC:C	acceptor_gain	0.9900
6:28579268:TCACC:T	donor_loss	0.9900
6:28579269:CA:C	donor_loss	0.9900
6:28579270:A:C	donor_loss	0.9900
6:28579277:T:C	donor_gain	0.9900
6:28579418:AC:A	acceptor_gain	0.9900
6:28579419:CC:C	acceptor_gain	0.9900
6:28579419:CCTGT:C	acceptor_gain	0.9900
6:28579420:C:CC	acceptor_gain	0.9900
6:28586292:TCTCA:T	donor_loss	0.9900
6:28586293:CTCAC:C	donor_loss	0.9900
6:28586294:TCA:T	donor_loss	0.9900
6:28586295:CAC:C	donor_loss	0.9900
6:28586296:A:AT	donor_loss	0.9900
6:28586297:CCT:C	donor_loss	0.9900
6:28586297:CCTG:C	donor_gain	0.9900
6:28573825:CATCT:C	acceptor_loss	0.9800
6:28573826:ATCTG:A	acceptor_loss	0.9800
6:28573827:TC:T	acceptor_loss	0.9800
6:28573828:C:A	acceptor_loss	0.9800
6:28573828:C:CC	acceptor_gain	0.9800
6:28573829:T:C	acceptor_loss	0.9800
6:28579264:ATTCT:A	donor_loss	0.9800
6:28579270:A:AC	donor_gain	0.9800
6:28579271:C:CC	donor_gain	0.9800

AlphaMissense

8798 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:28573335:A:G	C852R	0.996
6:28575668:A:G	L346P	0.996
6:28575773:A:G	L311P	0.996
6:28573333:G:C	C852W	0.995
6:28573562:A:G	L776P	0.995
6:28573651:A:C	F746L	0.995
6:28573651:A:T	F746L	0.995
6:28573653:A:G	F746L	0.995
6:28573562:A:T	L776H	0.994
6:28575672:A:C	Y345D	0.994
6:28575781:A:C	F308L	0.994
6:28575781:A:T	F308L	0.994
6:28575783:A:G	F308L	0.994
6:28575877:A:C	F276L	0.994
6:28575877:A:T	F276L	0.994
6:28575879:A:G	F276L	0.994
6:28575930:C:G	A259P	0.993
6:28573259:C:G	R877P	0.992
6:28573370:G:T	A840D	0.992
6:28576027:G:C	F226L	0.992
6:28576027:G:T	F226L	0.992
6:28576029:A:G	F226L	0.992
6:28573556:C:G	R778P	0.991
6:28573652:A:G	F746S	0.991
6:28572013:T:A	R1292S	0.990
6:28572013:T:G	R1292S	0.990
6:28573346:A:T	I848N	0.990
6:28575773:A:T	L311Q	0.990
6:28573247:A:G	L881P	0.989
6:28573350:A:G	C847R	0.989

dbSNP variants (sampled 300 via entrez): RS1000132932 (6:28616829 G>C), RS1000145115 (6:28598450 A>G), RS1000316884 (6:28589642 A>G), RS1000439885 (6:28598890 A>G), RS1000480560 (6:28605047 C>T), RS1000561356 (6:28604606 A>G), RS1000562011 (6:28593228 T>C), RS1000792826 (6:28618152 C>G,T), RS1000807971 (6:28586001 T>A,G), RS1000904806 (6:28585658 A>C,G), RS1000971684 (6:28575864 C>G,T), RS1001023114 (6:28610811 T>C), RS1001061449 (6:28611138 C>A), RS1001169279 (6:28572730 C>G,T), RS1001295253 (6:28580019 A>G)

Disease associations

OMIM: gene MIM:615254 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

30 associations (top):

Study	Trait	p-value
GCST003518_56	Daytime sleep phenotypes	2.000000e-07
GCST003901_17	Cognitive decline (age-related)	5.000000e-06
GCST004521_112	Autism spectrum disorder or schizophrenia	3.000000e-26
GCST004521_166	Autism spectrum disorder or schizophrenia	4.000000e-24
GCST004521_212	Autism spectrum disorder or schizophrenia	5.000000e-14
GCST004521_43	Autism spectrum disorder or schizophrenia	2.000000e-27
GCST004521_7	Autism spectrum disorder or schizophrenia	2.000000e-15
GCST004521_73	Autism spectrum disorder or schizophrenia	8.000000e-11
GCST004521_77	Autism spectrum disorder or schizophrenia	1.000000e-19
GCST004748_93	Lung cancer	1.000000e-12
GCST004749_76	Lung cancer in ever smokers	7.000000e-09
GCST004749_77	Lung cancer in ever smokers	3.000000e-08
GCST004750_43	Squamous cell lung carcinoma	1.000000e-11
GCST006291_64	Spherical equivalent or myopia (age of diagnosis)	3.000000e-10
GCST007326_89	Number of sexual partners	2.000000e-13
GCST008921_4	Asthma and major depressive disorder	2.000000e-11
GCST010083_321	Hemoglobin levels	1.000000e-17
GCST010142_16	Fish- and plant-related diet	2.000000e-10
GCST010142_19	Fish- and plant-related diet	4.000000e-10
GCST010142_34	Fish- and plant-related diet	7.000000e-09
GCST010142_35	Fish- and plant-related diet	8.000000e-09
GCST010142_42	Fish- and plant-related diet	1.000000e-08
GCST010142_7	Fish- and plant-related diet	3.000000e-12
GCST010241_127	Apolipoprotein A1 levels	9.000000e-25
GCST010702_75	Subcortical volume (MOSTest)	3.000000e-11
GCST010703_272	Brain morphology (MOSTest)	7.000000e-16
GCST010988_354	Adult body size	2.000000e-13
GCST012355_34	Depression	2.000000e-12
GCST90016674_3	Liver iron content	1.000000e-89
GCST90020028_836	Hip circumference adjusted for BMI	2.000000e-12

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0007828	daytime rest measurement
EFO:0004847	age at onset
EFO:0004509	hemoglobin measurement
EFO:0008111	diet measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004346	neuroimaging measurement
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
potassium chromate(VI)	affects cotreatment, increases expression, decreases expression	2
Benzo(a)pyrene	affects methylation, increases expression	2
bisphenol F	affects cotreatment, decreases methylation	1
urushiol	decreases expression	1
bisphenol A	decreases methylation	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
ferrous chloride	decreases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
avobenzone	decreases expression	1
chromium hexavalent ion	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
bisphenol S	affects cotreatment, decreases methylation	1
(+)-JQ1 compound	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Air Pollutants	increases abundance, increases expression	1
Dimethyl Sulfoxide	increases expression	1
Formaldehyde	increases expression	1
Methyl Methanesulfonate	increases expression	1
Quercetin	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Urethane	increases expression	1
Valproic Acid	increases expression	1
Cyclosporine	increases expression	1
Asbestos, Crocidolite	decreases methylation	1
Acrylamide	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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