SCRT2

Summary

SCRT2 (scratch family transcriptional repressor 2, HGNC:15952) is a protein-coding gene on chromosome 20p13, encoding Transcriptional repressor scratch 2 (Q9NQ03). May be involved in transcriptional regulation.

Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in negative regulation of extrinsic apoptotic signaling pathway via death domain receptors and negative regulation of transcription by RNA polymerase II. Predicted to act upstream of or within regulation of neuron migration. Predicted to be located in chromatin.

Source: NCBI Gene 85508 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 51 total — 1 pathogenic
• MANE Select transcript: NM_033129

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15952
Approved symbol	SCRT2
Name	scratch family transcriptional repressor 2
Location	20p13
Locus type	gene with protein product
Status	Approved
Aliases	ZNF898B
Ensembl gene	ENSG00000215397
Ensembl biotype	protein_coding
Entrez	85508

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000246104

RefSeq mRNA: 1 — MANE Select: NM_033129 NM_033129

CCDS: CCDS13006

Canonical transcript exons

ENST00000246104 — 2 exons

Exon	Start	End
ENSE00000858555	661596	664461
ENSE00001407286	675469	675802

Expression profiles

Bgee: expression breadth broad, 33 present calls, max score 95.52.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5930 / max 63.0392, expressed in 161 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
185984	0.3324	133
185987	0.2011	44
185985	0.0313	12
185986	0.0282	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	95.52	gold quality
cortical plate	UBERON:0005343	90.76	gold quality
primary visual cortex	UBERON:0002436	81.39	gold quality
ventricular zone	UBERON:0003053	71.87	gold quality
right hemisphere of cerebellum	UBERON:0014890	67.82	gold quality
cerebellum	UBERON:0002037	67.02	gold quality
cerebellar cortex	UBERON:0002129	66.83	gold quality
cerebellar hemisphere	UBERON:0002245	66.77	gold quality
superior frontal gyrus	UBERON:0002661	63.94	gold quality
right frontal lobe	UBERON:0002810	60.69	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	60.29	gold quality
Brodmann (1909) area 9	UBERON:0013540	59.25	gold quality
frontal cortex	UBERON:0001870	58.87	gold quality
colonic epithelium	UBERON:0000397	57.06	gold quality
prefrontal cortex	UBERON:0000451	57.05	gold quality
cerebral cortex	UBERON:0000956	56.70	gold quality
anterior cingulate cortex	UBERON:0009835	53.29	gold quality
islet of Langerhans	UBERON:0000006	53.08	gold quality
brain	UBERON:0000955	49.22	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	46.62	gold quality
substantia nigra	UBERON:0002038	46.50	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	45.52	gold quality
blood	UBERON:0000178	44.58	gold quality
bone marrow cell	CL:0002092	44.14	gold quality
temporal lobe	UBERON:0001871	42.42	gold quality
amygdala	UBERON:0001876	42.19	gold quality
Ammon’s horn	UBERON:0001954	42.19	gold quality
pancreas	UBERON:0001264	41.37	gold quality
putamen	UBERON:0001874	40.28	gold quality
sural nerve	UBERON:0015488	39.96	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.49

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA0744.1	SCRT2	More than 3 adjacent zinc fingers
MA0744.2	SCRT2	More than 3 adjacent zinc fingers
MA0744.3	SCRT2	More than 3 adjacent zinc fingers

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

miRNA regulators (miRDB)

127 targeting SCRT2, 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-6867-5P	100.00	82.21	3464
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085

Literature-anchored findings (GeneRIF, showing 1)

• Scratch2 and scratch1 are expressed upon neuronal fate commitment under the control of proneural genes to promote cell migration in the developing neocortex. (PMID:23434913)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	scrt2	ENSDARG00000056175
mus_musculus	Scrt2	ENSMUSG00000060257
rattus_norvegicus	Scrt2	ENSRNOG00000005148
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), SCRT1 (ENSG00000261678)

Protein

Protein identifiers

Transcriptional repressor scratch 2 — Q9NQ03 (reviewed: Q9NQ03)

Alternative names: Scratch homolog 2 zinc finger protein

All UniProt accessions (1): Q9NQ03

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in transcriptional regulation.

Subcellular location. Nucleus.

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

RefSeq proteins (1): NP_149120* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR050527

Pfam: PF00096

UniProt features (10 total): zinc finger region 5, region of interest 3, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NQ03-F1	57.46	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 142 (showing top): RRAGTTGT_UNKNOWN, AAGCAAT_MIR137, ACTACCT_MIR196A_MIR196B, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_NEUROGENESIS, LHX3_01, CAGGTCC_MIR492, CTATGCA_MIR153, USF_C, GCGCTTT_MIR518B_MIR518C_MIR518D, GOBP_NEGATIVE_REGULATION_OF_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_REGULATION_OF_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_VIA_DEATH_DOMAIN_RECEPTORS, NFKB_C, CDP_01, NKX62_Q2

GO Biological Process (4): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of DNA-templated transcription (GO:0006355), negative regulation of extrinsic apoptotic signaling pathway via death domain receptors (GO:1902042), regulation of neuron migration (GO:2001222)

GO Molecular Function (8): 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), zinc ion binding (GO:0008270), E-box binding (GO:0070888), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), metal ion binding (GO:0046872)

GO Cellular Component (2): chromatin (GO:0000785), 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	1
negative regulation of DNA-templated transcription	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
extrinsic apoptotic signaling pathway via death domain receptors	1
regulation of extrinsic apoptotic signaling pathway via death domain receptors	1
negative regulation of extrinsic apoptotic signaling pathway	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
transition metal ion binding	1
RNA polymerase II cis-regulatory region sequence-specific DNA binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
cation binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

642 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SCRT2	N4BP3	O15049	364
SCRT2	TRMT10B	Q6PF06	349
SCRT2	TTC34	A8MYJ7	322
SCRT2	TRAPPC3L	Q5T215	322
SCRT2	CD79B	P40259	306
SCRT2	SCAF11	Q99590	295
SCRT2	TFAP2D	Q7Z6R9	293
SCRT2	RASGEF1B	Q0VAM2	278
SCRT2	MXI1	P50539	276
SCRT2	DRGX	A6NNA5	275
SCRT2	NEUROG2	Q9H2A3	273
SCRT2	ZBTB3	Q9H5J0	273
SCRT2	ANKRD29	Q8N6D5	269
SCRT2	RFX3	P48380	268
SCRT2	LRRC23	Q53EV4	264

IntAct

2 interactions, top by confidence:

A	B	Type	Score
SCRT2	RECQL	psi-mi:“MI:0914”(association)	0.350

BioGRID (9): SCRT2 (Affinity Capture-MS), HIBCH (Affinity Capture-MS), SBDS (Affinity Capture-MS), S100A13 (Affinity Capture-MS), EEF1A2 (Affinity Capture-MS), RECQL (Affinity Capture-MS), SCRT2 (Affinity Capture-MS), SCRT2 (Affinity Capture-MS), SCRT2 (Affinity Capture-MS)

ESM2 similar proteins: A0A8I6AGW3, A2A9A2, A6NMB9, A8MYZ6, E9PZZ1, J3QK54, O02755, O02756, O35392, O35767, O60548, O70220, P05554, P17676, P21272, P28033, P35713, P42582, P49715, P49716, P52952, P53566, P58012, Q12952, Q13461, Q14526, Q60843, Q61345, Q63244, Q63250, Q6BEB4, Q6VFT5, Q6VFT6, Q6ZQN5, Q70KY4, Q8IU81, Q8MIP2, Q8NDY6, Q8R2I0, Q98937

Diamond homologs: A2ANX9, A7Y7X5, O43623, O62836, O95863, P08048, P10925, P17010, P17012, P19382, P20662, P25932, P28166, P31508, P31509, P80944, Q01611, Q01797, Q01798, Q01799, Q01800, Q02025, Q02026, Q02027, Q02085, Q29419, Q52V16, Q5RAU9, Q642B2, Q6B4Z5, Q6ZNH5, Q8BI66, Q8BTH6, Q8TF50, Q95LI3, Q99LH4, Q99M85, Q9BWW7, Q9ER74, Q9HAH1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	47
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1373812	NC_000020.10:g.(?389402)(746418_?)del	Pathogenic

SpliceAI

221 predictions. Top by Δscore:

Variant	Effect	Δscore
20:675465:TCAC:T	donor_loss	1.0000
20:675465:TCACC:T	donor_loss	1.0000
20:675466:CACCG:C	donor_loss	1.0000
20:675467:A:AC	donor_gain	1.0000
20:675467:AC:A	donor_gain	1.0000
20:675468:C:CA	donor_gain	1.0000
20:675468:C:CC	donor_gain	1.0000
20:675468:CC:C	donor_gain	1.0000
20:675468:CCG:C	donor_gain	1.0000
20:664460:CC:C	acceptor_gain	0.9900
20:664461:CC:C	acceptor_gain	0.9900
20:675468:CCGT:C	donor_gain	0.9900
20:675468:CCGTT:C	donor_gain	0.9800
20:664251:T:TA	donor_gain	0.9100
20:664462:C:CC	acceptor_gain	0.9100
20:664459:ACCC:A	acceptor_loss	0.9000
20:664462:C:A	acceptor_loss	0.9000
20:664463:T:A	acceptor_loss	0.9000
20:664458:TACC:T	acceptor_gain	0.8800
20:664269:T:TA	donor_gain	0.8600
20:663674:G:C	donor_gain	0.8500
20:664464:G:C	acceptor_loss	0.8400
20:662447:T:TA	donor_gain	0.8300
20:664462:C:T	acceptor_gain	0.8300
20:664457:GTACC:G	acceptor_gain	0.7800
20:664459:ACC:A	acceptor_gain	0.7800
20:664460:CCC:C	acceptor_gain	0.7800
20:672873:C:A	donor_gain	0.7700
20:664462:CT:C	acceptor_loss	0.7600
20:664463:T:TC	acceptor_loss	0.7600

AlphaMissense

1982 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:663764:G:C	F277L	1.000
20:663764:G:T	F277L	1.000
20:663765:A:G	F277S	1.000
20:663766:A:G	F277L	1.000
20:663787:A:G	C270R	1.000
20:663848:G:C	F249L	1.000
20:663848:G:T	F249L	1.000
20:663849:A:G	F249S	1.000
20:663850:A:G	F249L	1.000
20:663871:A:G	C242R	1.000
20:663932:G:C	F221L	1.000
20:663932:G:T	F221L	1.000
20:663934:A:G	F221L	1.000
20:663765:A:C	F277C	0.999
20:663786:C:G	C270S	0.999
20:663787:A:T	C270S	0.999
20:663809:G:C	H262Q	0.999
20:663809:G:T	H262Q	0.999
20:663821:G:C	H258Q	0.999
20:663821:G:T	H258Q	0.999
20:663823:G:C	H258D	0.999
20:663823:G:T	H258N	0.999
20:663831:A:G	L255P	0.999
20:663849:A:C	F249C	0.999
20:663850:A:T	F249I	0.999
20:663860:G:C	C245W	0.999
20:663861:C:G	C245S	0.999
20:663861:C:T	C245Y	0.999
20:663862:A:G	C245R	0.999
20:663862:A:T	C245S	0.999

dbSNP variants (sampled 300 via entrez): RS1000191534 (20:663299 G>A), RS1000290892 (20:674160 TTGA>T), RS1000349505 (20:670341 C>T), RS1000407895 (20:663015 G>C), RS1000713232 (20:669900 G>A), RS1000721049 (20:672072 A>G), RS1000746153 (20:664668 C>T), RS1000785729 (20:670588 C>T), RS1000949717 (20:663565 T>C), RS1001091309 (20:671838 C>T), RS1001266415 (20:675746 C>G,T), RS1001465986 (20:676985 T>C), RS1001496934 (20:677286 G>A), RS1001723711 (20:671284 C>T), RS1001916400 (20:665324 T>C)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:211530

GenCC curated gene-disease

Mondo (1): Brown-Vialetto-van Laere syndrome 1 (MONDO:0024537)

Orphanet (2): RFVT2-related riboflavin transporter deficiency (Orphanet:572543), Riboflavin transporter deficiency (Orphanet:97229)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005355_1	Helping behaviour (self reported)	7.000000e-10

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aflatoxin B2	increases methylation	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Endosulfan	decreases expression	1
Niclosamide	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases 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_XV82	HEK293 eGFP-SCRT2	Transformed cell line	Female

Clinical trials (associated diseases)

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