SCRT1

Summary

SCRT1 (scratch family transcriptional repressor 1, HGNC:15950) is a protein-coding gene on chromosome 8q24.3, encoding Transcriptional repressor scratch 1 (Q9BWW7). Transcriptional repressor that binds E-box motif CAGGTG.

This gene encodes a C2H2-type zinc finger transcriptional repressor that binds to E-box motifs. The encoded protein may promote neural differention and may be involved in cancers with neuroendocrine features.

Source: NCBI Gene 83482 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 40 total
• MANE Select transcript: NM_031309

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15950
Approved symbol	SCRT1
Name	scratch family transcriptional repressor 1
Location	8q24.3
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp547F072, ZNF898
Ensembl gene	ENSG00000261678
Ensembl biotype	protein_coding
OMIM	605858
Entrez	83482

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000569446

RefSeq mRNA: 1 — MANE Select: NM_031309 NM_031309

CCDS: CCDS6421

Canonical transcript exons

ENST00000569446 — 2 exons

Exon	Start	End
ENSE00002604471	144330565	144334116
ENSE00002619090	144336055	144336482

Expression profiles

Bgee: expression breadth broad, 51 present calls, max score 97.56.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.8705 / max 125.0572, expressed in 114 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
95651	0.4255	88
95650	0.3905	81
95646	0.0545	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primary visual cortex	UBERON:0002436	97.56	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.49	gold quality
cerebellum	UBERON:0002037	94.33	gold quality
cerebellar cortex	UBERON:0002129	94.32	gold quality
cerebellar hemisphere	UBERON:0002245	94.30	gold quality
superior frontal gyrus	UBERON:0002661	92.59	gold quality
right frontal lobe	UBERON:0002810	92.51	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.97	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.00	gold quality
cortical plate	UBERON:0005343	89.34	gold quality
frontal cortex	UBERON:0001870	89.21	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.29	gold quality
cerebral cortex	UBERON:0000956	88.12	gold quality
anterior cingulate cortex	UBERON:0009835	87.38	gold quality
prefrontal cortex	UBERON:0000451	86.71	gold quality
putamen	UBERON:0001874	86.55	gold quality
brain	UBERON:0000955	85.16	gold quality
caudate nucleus	UBERON:0001873	84.75	gold quality
substantia nigra	UBERON:0002038	84.10	gold quality
Ammon’s horn	UBERON:0001954	83.65	gold quality
nucleus accumbens	UBERON:0001882	83.04	gold quality
ganglionic eminence	UBERON:0004023	81.87	gold quality
hypothalamus	UBERON:0001898	80.94	gold quality
temporal lobe	UBERON:0001871	80.38	gold quality
amygdala	UBERON:0001876	80.21	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	72.03	gold quality
pituitary gland	UBERON:0000007	64.79	gold quality
adenohypophysis	UBERON:0002196	61.03	gold quality
ventricular zone	UBERON:0003053	59.26	gold quality
islet of Langerhans	UBERON:0000006	58.41	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
SLC6A2
TUBB3

JASPAR motifs

Motif	Name	Family
MA0743.1	SCRT1	More than 3 adjacent zinc fingers
MA0743.2	SCRT1	More than 3 adjacent zinc fingers
MA0743.3	SCRT1	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:11274425, PMID:23332764

Upstream regulators (CollecTRI, top): ASCL1, NEUROD2, TCF3

miRNA regulators (miRDB)

88 targeting SCRT1, 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-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-3960	99.41	66.11	96

Literature-anchored findings (GeneRIF, showing 3)

• SCRT1 is a novel beta cell transcription factor with insulin regulatory properties. (PMID:33309639)
• Scrt1, a transcriptional regulator of beta-cell proliferation identified by differential chromatin accessibility during islet maturation. (PMID:33888791)
• Long non-coding RNA TCL6 induced by SCRT1 promotes proliferation and metastasis of non-small cell lung cancer through PDK1/AKT signaling. (PMID:37141697)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	scrt1b	ENSDARG00000040214
danio_rerio	scrt1a	ENSDARG00000100821
mus_musculus	Scrt1	ENSMUSG00000048385
rattus_norvegicus	Scrt1	ENSRNOG00000025594
drosophila_melanogaster	scrt	FBGN0004880
drosophila_melanogaster	Kah	FBGN0035144
drosophila_melanogaster	CG12605	FBGN0035481
caenorhabditis_elegans	ces-1	WBGENE00000468
caenorhabditis_elegans	scrt-1	WBGENE00016948

Paralogs (36): ZBTB32 (ENSG00000011590), SNAI2 (ENSG00000019549), PRDM1 (ENSG00000057657), PRDM6 (ENSG00000061455), ZNF76 (ENSG00000065029), PATZ1 (ENSG00000100105), MAZ (ENSG00000103495), ZBTB16 (ENSG00000109906), ZNF451 (ENSG00000112200), ZBTB45 (ENSG00000119574), ZNF410 (ENSG00000119725), SNAI1 (ENSG00000124216), ZNF384 (ENSG00000126746), ZBTB1 (ENSG00000126804), VEZF1 (ENSG00000136451), PRDM14 (ENSG00000147596), ZNF276 (ENSG00000158805), ZNF362 (ENSG00000160094), ZNF653 (ENSG00000161914), ZNF281 (ENSG00000162702), ZNF148 (ENSG00000163848), ZNF143 (ENSG00000166478), HIC2 (ENSG00000169635), PRDM10 (ENSG00000170325), ZNF296 (ENSG00000170684), ZNF692 (ENSG00000171163), ZNF575 (ENSG00000176472), HIC1 (ENSG00000177374), ZBTB18 (ENSG00000179456), ZBTB42 (ENSG00000179627), ZBTB20 (ENSG00000181722), ZBTB7C (ENSG00000184828), SNAI3 (ENSG00000185669), ZFP91 (ENSG00000186660), MTF1 (ENSG00000188786), SCRT2 (ENSG00000215397)

Protein

Protein identifiers

Transcriptional repressor scratch 1 — Q9BWW7 (reviewed: Q9BWW7)

Alternative names: Scratch homolog 1 zinc finger protein

All UniProt accessions (1): Q9BWW7

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional repressor that binds E-box motif CAGGTG. Can modulate the action of basic helix-loop-helix (bHLH) transcription factors, critical for neuronal differentiation.

Subunit / interactions. Interacts (via SNAG domain) with LIMD1 (via LIM domains), WTIP (via LIM domains) and AJUBA (via LIM domains).

Subcellular location. Nucleus.

Tissue specificity. Brain specific.

Domain organisation. The N-terminal non zinc-finger region mediates the repressor activity.

Similarity. Belongs to the snail C2H2-type zinc-finger protein family.

RefSeq proteins (1): NP_112599* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR050527

Pfam: PF00096, PF13912

UniProt features (12 total): zinc finger region 5, compositionally biased region 3, region of interest 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BWW7-F1	54.75	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 109 (showing top): TAATAAT_MIR126, AAGCCAT_MIR135A_MIR135B, GTCTACC_MIR379, GOBP_NEUROGENESIS, CTCTAGA_MIR526C_MIR518F_MIR526A, GOBP_REGULATION_OF_NEURON_MIGRATION, GOBP_NEURON_MIGRATION, GOCC_NUCLEAR_BODY, KIM_WT1_TARGETS_DN, GGGGCCC_MIR296, GSE13522_WT_VS_IFNG_KO_SKIN_DN, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, MEISSNER_BRAIN_HCP_WITH_H3K4ME3_AND_H3K27ME3, MEISSNER_NPC_HCP_WITH_H3K4ME2_AND_H3K27ME3, MIKKELSEN_MCV6_HCP_WITH_H3K27ME3

GO Biological Process (4): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of DNA-templated transcription (GO:0006355), regulation of neuron migration (GO:2001222), regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (10): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription factor activity (GO:0003700), zinc ion binding (GO:0008270), sequence-specific DNA binding (GO:0043565), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), metal ion binding (GO:0046872)

GO Cellular Component (2): nuclear body (GO:0016604), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
regulation of DNA-templated transcription	2
transcription cis-regulatory region binding	2
negative regulation of DNA-templated transcription	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
neuron migration	1
regulation of cell migration	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription repressor activity	1
transcription regulator activity	1
transition metal ion binding	1
DNA binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
cation binding	1
nucleoplasm	1
intracellular membraneless organelle	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1688 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SCRT1	SLC6A2	P23975	810
SCRT1	ASCL1	P50553	643
SCRT1	PRRG4	Q9BZD6	415
SCRT1	GATA3	P23771	410
SCRT1	SDR16C5	Q8N3Y7	410
SCRT1	ADCK5	Q3MIX3	401
SCRT1	FBXL6	Q8N531	397
SCRT1	CEP41	Q9BYV8	396
SCRT1	GABARAP	O95166	382
SCRT1	PALM3	A6NDB9	369
SCRT1	GAD1	Q99259	360
SCRT1	SLC17A6	Q9P2U8	349
SCRT1	HP	P00737	344
SCRT1	STMP1	E0CX11	342
SCRT1	GATAD2B	Q8WXI9	335

IntAct

3 interactions, top by confidence:

A	B	Type	Score
NES	SYNM	psi-mi:“MI:0914”(association)	0.350
SCRT1	IMPDH1	psi-mi:“MI:0914”(association)	0.350

BioGRID (9): IMPDH1 (Affinity Capture-MS), ZNF579 (Affinity Capture-MS), WWP1 (Affinity Capture-MS), PRMT9 (Affinity Capture-MS), SCRT1 (Affinity Capture-MS), SORL1 (Affinity Capture-MS), KLHDC10 (Affinity Capture-MS), VRK3 (Affinity Capture-MS), SCRT1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GUA5, A0A286YF58, A0A494C0N9, A0A494C0Y3, A0A7I2V3R4, A0JNN8, A2ARS0, A2VDX9, A5PJP1, A6NGB7, A8MVW0, C9JTQ0, O14511, O14559, O35392, O35569, O43541, O60548, O70220, P0DPE3, Q08102, Q14V87, Q19A40, Q29RK8, Q2HJ59, Q3TYP4, Q5BLP8, Q5T442, Q63244, Q6F5E0, Q6QNY0, Q6VUP9, Q80WY3, Q80XF7, Q8BQU6, Q8K025, Q8K071, Q8TD94, Q8WY41, Q8WZ71

Diamond homologs: A1L2U9, A2A884, A2ANX9, A7Y7X5, B0X9H6, B0YDH7, B1WAZ8, B1WBU4, E9PW05, E9PZZ1, G5EBU4, O15391, O60315, O62836, O75362, O77459, O95863, P08048, P0CS62, P0CS63, P10925, P15822, P17010, P17012, P20662, P22227, P25490, P28166, P31509, P31629, P36197, P52739, P52746, P56270, P56670, P56671, P60319, P80944, Q00899, Q00900

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

213 predictions. Top by Δscore:

Variant	Effect	Δscore
8:144336050:CTCA:C	donor_loss	1.0000
8:144336051:TCAC:T	donor_loss	1.0000
8:144336053:A:AC	donor_gain	1.0000
8:144336053:AC:A	donor_gain	1.0000
8:144336054:C:CC	donor_gain	1.0000
8:144336054:CC:C	donor_gain	1.0000
8:144336054:CCTTT:C	donor_gain	1.0000
8:144336054:CCT:C	donor_gain	0.9900
8:144336054:CCTT:C	donor_gain	0.9900
8:144336051:TCACC:T	donor_gain	0.9500
8:144334115:CC:C	acceptor_gain	0.9400
8:144334116:CC:C	acceptor_gain	0.9400
8:144336052:CACCT:C	donor_gain	0.9400
8:144336053:ACCTT:A	donor_gain	0.9100
8:144336049:GCTCA:G	donor_gain	0.8700
8:144336050:CTCAC:C	donor_gain	0.8700
8:144336054:C:G	donor_gain	0.8500
8:144333131:C:A	donor_gain	0.8400
8:144334117:CT:C	acceptor_loss	0.8000
8:144334117:C:CC	acceptor_gain	0.7600
8:144334124:C:CT	acceptor_gain	0.7500
8:144333854:ACG:A	donor_gain	0.7400
8:144333855:CGC:C	donor_gain	0.7400
8:144333855:CGCCG:C	donor_gain	0.7300
8:144334113:TACC:T	acceptor_gain	0.7300
8:144333855:CG:C	donor_gain	0.7100
8:144334114:ACC:A	acceptor_gain	0.7100
8:144334115:CCC:C	acceptor_gain	0.7100
8:144334125:G:T	acceptor_gain	0.7100
8:144334112:GTACC:G	acceptor_gain	0.7000

AlphaMissense

2227 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:144333266:G:C	H322Q	1.000
8:144333266:G:T	H322Q	1.000
8:144333268:G:C	H322D	1.000
8:144333276:A:G	L319P	1.000
8:144333293:G:C	F313L	1.000
8:144333293:G:T	F313L	1.000
8:144333294:A:C	F313C	1.000
8:144333294:A:G	F313S	1.000
8:144333295:A:G	F313L	1.000
8:144333306:C:G	C309S	1.000
8:144333307:A:G	C309R	1.000
8:144333307:A:T	C309S	1.000
8:144333314:G:C	C306W	1.000
8:144333315:C:G	C306S	1.000
8:144333316:A:G	C306R	1.000
8:144333316:A:T	C306S	1.000
8:144333320:G:C	F304L	1.000
8:144333320:G:T	F304L	1.000
8:144333322:A:G	F304L	1.000
8:144333338:A:C	H298Q	1.000
8:144333338:A:T	H298Q	1.000
8:144333350:G:C	H294Q	1.000
8:144333350:G:T	H294Q	1.000
8:144333352:G:C	H294D	1.000
8:144333352:G:T	H294N	1.000
8:144333360:A:G	L291P	1.000
8:144333377:G:C	F285L	1.000
8:144333377:G:T	F285L	1.000
8:144333378:A:G	F285S	1.000
8:144333379:A:G	F285L	1.000

dbSNP variants (sampled 300 via entrez): RS1000210517 (8:144331780 G>A), RS1000368577 (8:144337891 G>A,C), RS1000986647 (8:144336123 G>A), RS1002165871 (8:144332701 C>T), RS1002604547 (8:144330211 G>A), RS1004221611 (8:144337602 G>A), RS1004239772 (8:144334511 T>A,C), RS1004277939 (8:144331254 C>T), RS1004450842 (8:144337243 G>A), RS1004908792 (8:144337382 G>A,T), RS1005897177 (8:144332216 G>A,C), RS1005947562 (8:144332432 C>T), RS1006681891 (8:144335306 G>A,T), RS1007040628 (8:144335161 T>C), RS1007631422 (8:144333244 C>G,T)

Disease associations

OMIM: gene MIM:605858 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002598_30	Educational attainment	9.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004784	self reported educational attainment

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
potassium chromate(VI)	affects cotreatment, increases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
abrine	increases expression	1
licochalcone B	increases expression	1
Benzo(a)pyrene	increases methylation	1
Formaldehyde	increases expression	1
Niclosamide	increases expression	1
Thimerosal	increases expression	1
Valproic Acid	increases methylation	1
Okadaic Acid	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_XV81	HEK293 eGFP-SCRT1	Transformed cell line	Female

Clinical trials (associated diseases)

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