SRRT

Summary

SRRT (serrate, RNA effector molecule, HGNC:24101) is a protein-coding gene on chromosome 7q22.1, encoding Serrate RNA effector molecule homolog (Q9BXP5). Acts as a mediator between the cap-binding complex (CBC) and the primary microRNAs (miRNAs) processing machinery during cell proliferation. It is a common-essential gene (DepMap: required in 91.6% of cancer cell lines).

Enables mRNA cap binding complex binding activity and protein-macromolecule adaptor activity. Involved in primary miRNA processing. Located in nucleoplasm. Part of ribonucleoprotein complex.

Source: NCBI Gene 51593 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 151 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 91.6% of screened cell lines (common-essential)
• MANE Select transcript: NM_015908

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24101
Approved symbol	SRRT
Name	serrate, RNA effector molecule
Location	7q22.1
Locus type	gene with protein product
Status	Approved
Aliases	Asr2, serrate, ARS2
Ensembl gene	ENSG00000087087
Ensembl biotype	protein_coding
OMIM	614469
Entrez	51593

Gene structure

Transcript identifiers

Ensembl transcripts: 45 — 32 protein_coding, 8 retained_intron, 4 nonsense_mediated_decay, 1 non_stop_decay

ENST00000423692, ENST00000431645, ENST00000445337, ENST00000448764, ENST00000449389, ENST00000460194, ENST00000466432, ENST00000469602, ENST00000474896, ENST00000477529, ENST00000478693, ENST00000487311, ENST00000611405, ENST00000614370, ENST00000614484, ENST00000618262, ENST00000618411, ENST00000620394, ENST00000641476, ENST00000860832, ENST00000860833, ENST00000860834, ENST00000860835, ENST00000860836, ENST00000860837, ENST00000860838, ENST00000860839, ENST00000935245, ENST00000935246, ENST00000935247, ENST00000935248, ENST00000935249, ENST00000935250, ENST00000935251, ENST00000965064, ENST00000965065, ENST00000965066, ENST00000965067, ENST00000965068, ENST00000965069, ENST00000965070, ENST00000965071, ENST00000965072, ENST00000965073, ENST00000965074

RefSeq mRNA: 4 — MANE Select: NM_015908 NM_001128852, NM_001128853, NM_001128854, NM_015908

CCDS: CCDS34709, CCDS47665, CCDS47666, CCDS47667

Canonical transcript exons

ENST00000611405 — 20 exons

Exon	Start	End
ENSE00000710116	100885213	100885370
ENSE00002433338	100888042	100888143
ENSE00002501461	100887320	100887513
ENSE00002505547	100886795	100886968
ENSE00002514991	100885701	100885762
ENSE00002721861	100882053	100882241
ENSE00003552923	100886247	100886435
ENSE00003586721	100887047	100887200
ENSE00003655947	100881285	100881413
ENSE00003670070	100885863	100885941
ENSE00003690603	100887703	100887859
ENSE00003720477	100881659	100881805
ENSE00003722482	100888257	100888383
ENSE00003731949	100875103	100875328
ENSE00003739209	100888474	100888664
ENSE00003743171	100884368	100884552
ENSE00003744313	100884740	100884838
ENSE00003745047	100875573	100875712
ENSE00003751523	100884070	100884239
ENSE00003754853	100884923	100885040

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 71.8903 / max 479.5170, expressed in 1825 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
80062	66.2264	1825
80061	3.0533	1328
80063	1.3597	755
80066	0.5054	139
80065	0.4360	238
204546	0.2079	67
80064	0.1015	23

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	99.35	gold quality
right testis	UBERON:0004534	99.33	gold quality
sural nerve	UBERON:0015488	98.88	gold quality
adenohypophysis	UBERON:0002196	98.77	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.67	gold quality
right lobe of thyroid gland	UBERON:0001119	98.61	gold quality
pituitary gland	UBERON:0000007	98.60	gold quality
metanephros cortex	UBERON:0010533	98.52	gold quality
cerebellar hemisphere	UBERON:0002245	98.51	gold quality
endocervix	UBERON:0000458	98.47	gold quality
left lobe of thyroid gland	UBERON:0001120	98.47	gold quality
cerebellar cortex	UBERON:0002129	98.45	gold quality
lower esophagus mucosa	UBERON:0035834	98.45	gold quality
right ovary	UBERON:0002118	98.44	gold quality
left ovary	UBERON:0002119	98.43	gold quality
right uterine tube	UBERON:0001302	98.42	gold quality
granulocyte	CL:0000094	98.40	gold quality
body of uterus	UBERON:0009853	98.34	gold quality
left uterine tube	UBERON:0001303	98.26	gold quality
testis	UBERON:0000473	98.25	gold quality
ectocervix	UBERON:0012249	98.24	gold quality
skin of abdomen	UBERON:0001416	98.23	gold quality
adult organism	UBERON:0007023	98.22	gold quality
spleen	UBERON:0002106	98.21	gold quality
ventricular zone	UBERON:0003053	98.15	gold quality
thyroid gland	UBERON:0002046	98.14	gold quality
skin of leg	UBERON:0001511	98.09	gold quality
minor salivary gland	UBERON:0001830	98.08	gold quality
mucosa of stomach	UBERON:0001199	98.07	gold quality
small intestine Peyer’s patch	UBERON:0003454	98.03	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.94

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

9 targeting SRRT, 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-302E	99.96	70.74	2669
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-374B-3P	98.63	68.24	1360
HSA-MIR-3929	98.32	65.58	1026
HSA-MIR-4700-3P	97.74	68.64	1014
HSA-MIR-3190-3P	97.61	66.95	1406

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 91.6% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 21)

• Nomenclature. Original paper and GenBank submission by Rossman and Wang (1999) called the gene Asr2 (arsenite resistance protein 2) as opposed to Ars2 (arsenate resistance protein 2). (PMID:10069470)
• Validated occurrence of an unusual TG 3’ splice site in intron 17 (NM_015908). (PMID:17672918)
• These data indicate ARS2 is essential for early mammalian development and is likely involved in an essential cellular process. (PMID:18086880)
• Results suggest that FLASH functions in S phase progression through interaction with ARS2. (PMID:19546234)
• These findings provide evidence for a role for Ars2 in RNA interference regulation during cell proliferation. (PMID:19632182)
• Ars2 is overexpressed in human cholangiocarcinoma and may be a diagnostic marker. Ars2 depletion increases PTEN and PDCD4 protein levels via the reduction of miR-21. (PMID:22213145)
• Ars2 contributes to histone mRNA 3’ end formation and expression and these functional properties of Ars2 are negatively regulated by interaction with 7SK RNA. (PMID:22244333)
• Ars2 is overexpressed in HCC and may have prognostic value; it might play an important role in HCC proliferation and miR-21 expression. (PMID:24272391)
• ARS2 and CASP8AP2 expressions can precisely predict high-risk of relapse and ALL prognosis. (PMID:25530566)
• 2,3,5,6-Tetramethylpyrazine (TMP) down-regulated arsenic-induced heme oxygenase-1 and ARS2 expression by inhibiting Nrf2, NF-kappaB, AP-1 and MAPK pathways in human proximal tubular cells. (PMID:26404762)
• ARS2 depletion negatively impacts levels of promoter-proximal RNA polymerase II at protein-coding genes. It is involved in transcription termination events within first introns of pc genes. ARS2 plays a role in transcription termination-coupled RNA turnover at short transcription units like snRNA-, replication-dependent histone-, promoter upstream transcript- and enhancer RNA-loci. (PMID:28973446)
• define two mutually exclusive complexes CBC-NELF-E and CBC-ARS2-PHAX, which likely act in respectively earlier and later phases of transcription (PMID:29101316)
• Study present the human ARS2 crystal structure, which exhibits similarities and metazoan-specific differences to the plant homologue SERRATE, most notably an additional RRM domain. RRM domain is required to bind RNA, whereas a basic patch in the C-terminal leg of ARS2 mediates the interaction with FLASH. (PMID:29703953)
• Deletion of Ars2 from adult mice resulted in defective hematopoiesis in bone marrow and thymus.Ars2 was required for survival of developing thymocytes and for limiting differentiation of bone marrow resident long-term hematopoietic stem cells. Ars2 knockout led to rapid thymic involution and loss of the ability of mice to regenerate peripheral blood after myeloablation. (PMID:29775646)
• Overexpression of Ars2 promoted cell proliferation and colony formation in glioblastoma cells, whereas the depletion of Ars2 inhibited cell proliferation, colony formation, and tumor growth. Knockdown of Ars2 reduced the expression levels of miR-6798-3p. (PMID:30349053)
• Depletion of Ars2 reduced the level of miR-6734-3p by inhibiting the interaction of Ars2 with either CBC complex or Drosha, leading to p27 up-regulation-mediated G1 cell cycle arrest, and culminating in inhibition of cell proliferation and leukemogenesis in AML (PMID:30518811)
• Ars2 deficiency inhibited the activation of the MAPK/ERK pathway, leading to cell cycle arrest in the G1 phase, resulting in suppression of glioblastoma cell proliferation. (PMID:30542699)
• In the present study, the authors demonstrate that ARS2 regulates both the 3=-end processing and stability of NEAT1. (PMID:31818879)
• Mapping domains of ARS2 critical for its RNA decay capacity. (PMID:32463452)
• ARS2/MAGL signaling in glioblastoma stem cells promotes self-renewal and M2-like polarization of tumor-associated macrophages. (PMID:32532977)
• ARS2/SRRT: at the nexus of RNA polymerase II transcription, transcript maturation and quality control. (PMID:34060620)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	srrt	ENSDARG00000017762
mus_musculus	Srrt	ENSMUSG00000037364
rattus_norvegicus	Srrt	ENSRNOG00000048277
drosophila_melanogaster	Ars2	FBGN0033062
caenorhabditis_elegans	srrt-1	WBGENE00017085

Protein

Protein identifiers

Serrate RNA effector molecule homolog — Q9BXP5 (reviewed: Q9BXP5)

Alternative names: Arsenite-resistance protein 2

All UniProt accessions (8): Q9BXP5, A0A087X0F4, A0A0A0MSP6, A0A286YEP7, C9JUL9, H7C0U8, H7C1K0, H7C3A1

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a mediator between the cap-binding complex (CBC) and the primary microRNAs (miRNAs) processing machinery during cell proliferation. Contributes to the stability and delivery of capped primary miRNA transcripts to the primary miRNA processing complex containing DGCR8 and DROSHA, thereby playing a role in RNA-mediated gene silencing (RNAi) by miRNAs. Binds capped RNAs (m7GpppG-capped RNA); however interaction is probably mediated via its interaction with NCBP1/CBP80 component of the CBC complex. Involved in cell cycle progression at S phase. Does not directly confer arsenite resistance but rather modulates arsenic sensitivity. Independently of its activity on miRNAs, necessary and sufficient to promote neural stem cell self-renewal. Does so by directly binding SOX2 promoter and positively regulating its transcription.

Subunit / interactions. Interacts with NCBP1 and DROSHA. Interacts with CASP8AP2 and ERBB4. Interacts with LUZP4. Interacts with NCBP2/CBP20 and NCBP3. Interacts with MTREX.

Subcellular location. Nucleus. Nucleoplasm. Cytoplasm.

Tissue specificity. Ubiquitously expressed.

Similarity. Belongs to the ARS2 family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q9BXP5-1	1, A	yes
Q9BXP5-2	2, B
Q9BXP5-3	3
Q9BXP5-4	4
Q9BXP5-5	5

RefSeq proteins (4): NP_001122324, NP_001122325, NP_001122326, NP_056992* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007042	SERRATE/Ars2_C	Domain
IPR021933	SERRATE/Ars2_N	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR039727	SE/Ars2	Family

Pfam: PF04959, PF12066

UniProt features (79 total): helix 22, modified residue 15, strand 14, sequence conflict 8, turn 5, region of interest 4, splice variant 4, compositionally biased region 4, initiator methionine 1, chain 1, cross-link 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
5OO6	X-RAY DIFFRACTION	2.8
6F7J	X-RAY DIFFRACTION	3.22
6F7S	X-RAY DIFFRACTION	3.37
8PMP	ELECTRON MICROSCOPY	3.43
6F8D	X-RAY DIFFRACTION	3.48
6F7P	X-RAY DIFFRACTION	3.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BXP5-F1	66.61	0.29

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (16): 2, 4, 8, 67, 74, 136, 493, 540, 544, 570, 671, 679, 833, 840, 850, 150

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-6807505	RNA polymerase II transcribes snRNA genes
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-9770562	mRNA Polyadenylation
R-HSA-9918481	Dengue Virus-Host Interactions
R-HSA-9930044	Nuclear RNA decay
R-HSA-72172	mRNA Splicing
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 170 (showing top): GOBP_NEUROGENESIS, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, RIZKI_TUMOR_INVASIVENESS_3D_DN, GOBP_POSITIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, MORF_RAF1, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_CDC25_UP, GOBP_POSITIVE_REGULATION_OF_CELL_DIFFERENTIATION, BLALOCK_ALZHEIMERS_DISEASE_UP, REACTOME_MRNA_3_END_PROCESSING, MORF_FANCG, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_MAINTENANCE_OF_CELL_NUMBER, GARY_CD5_TARGETS_DN, REACTOME_MRNA_SPLICING, GOBP_NEURONAL_STEM_CELL_POPULATION_MAINTENANCE

GO Biological Process (6): regulation of DNA-templated transcription (GO:0006355), primary miRNA processing (GO:0031053), response to arsenic-containing substance (GO:0046685), positive regulation of neurogenesis (GO:0050769), neuronal stem cell population maintenance (GO:0097150), regulatory ncRNA-mediated gene silencing (GO:0031047)

GO Molecular Function (6): DNA binding (GO:0003677), RNA binding (GO:0003723), protein-macromolecule adaptor activity (GO:0030674), mRNA cap binding complex binding (GO:0140262), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (6): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), nuclear body (GO:0016604), protein-containing complex (GO:0032991), ribonucleoprotein complex (GO:1990904), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Metabolism of RNA	2
RNA Polymerase II Transcription	1
mRNA Splicing	1
mRNA 3’-end processing	1
Dengue Virus Infection	1
Processing of Capped Intron-Containing Pre-mRNA	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nucleic acid binding	2
binding	2
cellular anatomical structure	2
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
miRNA processing	1
response to chemical	1
positive regulation of cell development	1
neurogenesis	1
regulation of neurogenesis	1
positive regulation of nervous system development	1
stem cell population maintenance	1
negative regulation of gene expression	1
protein binding	1
molecular adaptor activity	1
protein-containing complex binding	1
nuclear lumen	1
intracellular anatomical structure	1
nucleoplasm	1
intracellular membraneless organelle	1
cellular_component	1
protein-containing complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2246 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SRRT	NCBP2	P52298	973
SRRT	GNLY	P09325	969
SRRT	NOTCH1	P46531	960
SRRT	NCBP1	Q09161	949
SRRT	JAG1	P78504	915
SRRT	PHAX	Q9H814	888
SRRT	JAG2	Q9Y219	868
SRRT	DLL3	Q9NYJ7	867
SRRT	DROSHA	Q9NRR4	839
SRRT	NOTCH2	Q04721	818
SRRT	NOTCH4	Q99466	785
SRRT	DICER1	Q9UPY3	785
SRRT	ALYREF	Q86V81	784
SRRT	EGF	P01133	782
SRRT	ZFC3H1	O60293	770

IntAct

187 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
SNRPD2	GEMIN2	psi-mi:“MI:0914”(association)	0.710
THOC1	EIF4A3	psi-mi:“MI:0914”(association)	0.660
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
NCBP1	KPNA3	psi-mi:“MI:0914”(association)	0.640
SF3B1	SAP18	psi-mi:“MI:0914”(association)	0.640
SNRNP40	PRPF4	psi-mi:“MI:0914”(association)	0.640
THOC1	DDX39A	psi-mi:“MI:0914”(association)	0.640
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
SRRT	CACNA1C	psi-mi:“MI:0915”(physical association)	0.550
SNRPF	SRRT	psi-mi:“MI:0915”(physical association)	0.550
DLD	PDHB	psi-mi:“MI:0914”(association)	0.530
NCBP3	KPNA3	psi-mi:“MI:0914”(association)	0.530
NCBP2	KPNA4	psi-mi:“MI:0914”(association)	0.530
ELAVL2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
SOST	KPNA4	psi-mi:“MI:0914”(association)	0.530
ZC3H18	AQR	psi-mi:“MI:0914”(association)	0.530
ZFC3H1	HNRNPCL1	psi-mi:“MI:0914”(association)	0.530
SNRPC	SNRPGP15	psi-mi:“MI:0914”(association)	0.530
THOC5	EIF4A3	psi-mi:“MI:0914”(association)	0.530
ZC3H18	SRPK2	psi-mi:“MI:0914”(association)	0.530

BioGRID (428): SRRT (Affinity Capture-MS), SRRT (Affinity Capture-MS), SRRT (Affinity Capture-MS), SRRT (Affinity Capture-MS), SRRT (Affinity Capture-MS), SRRT (Affinity Capture-Western), SRRT (Affinity Capture-MS), SRRT (Affinity Capture-MS), SRRT (Affinity Capture-MS), SRRT (Affinity Capture-MS), SRRT (Affinity Capture-MS), EEF1D (Co-fractionation), OGFOD1 (Co-fractionation), PRKCSH (Co-fractionation), PSME3 (Co-fractionation)

ESM2 similar proteins: A0JM64, A0JMV4, A2VDN6, A4IFB1, A4IGK4, D3ZTQ1, O70523, O75400, P35922, P51113, P51114, P51115, P70501, P98175, Q06787, Q12872, Q15459, Q2KHP9, Q2KIA6, Q2NLB0, Q2TBT7, Q3TCX3, Q3USH5, Q5BJ56, Q5R539, Q5R9B4, Q5SFM8, Q5T8P6, Q5XI81, Q61584, Q66I22, Q6DDU9, Q6GLC9, Q6NZ18, Q6NZN0, Q7TN31, Q80TJ7, Q80WE1, Q8CGC4, Q8JZX4

Diamond homologs: A4IFB1, A8XEG9, B1H1X4, B3MJ69, B3N3F7, B4H732, B4II37, B4J497, B4KLY7, B4LIK8, B4MR46, B4NYV0, B4QCR6, Q17FR9, Q28WQ8, Q5R539, Q5TUF1, Q60436, Q66I22, Q6INH5, Q966L5, Q99MR6, Q9BXP5, Q9V9K7, Q9ZVD0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 198 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Transport of Mature Transcript to Cytoplasm	10	24.9×	2e-10
mRNA 3’-end processing	18	23.2×	2e-18
RNA Polymerase II Transcription Termination	16	23.0×	3e-16
Processing of Intronless Pre-mRNAs	6	22.4×	8e-06
Metabolism of non-coding RNA	5	20.7×	1e-04
mRNA Splicing	27	19.4×	2e-25
Processing of Capped Intron-Containing Pre-mRNA	34	18.3×	2e-31
mRNA Splicing - Minor Pathway	11	16.1×	3e-09

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of mRNA splicing, via spliceosome	8	34.6×	8e-09
U2-type prespliceosome assembly	9	31.7×	2e-09
spliceosomal complex assembly	9	30.6×	2e-09
RNA export from nucleus	5	26.4×	9e-05
regulation of mRNA splicing, via spliceosome	5	25.1×	1e-04
spliceosomal snRNP assembly	7	23.0×	2e-06
RNA splicing, via transesterification reactions	6	21.2×	3e-05
alternative mRNA splicing, via spliceosome	5	19.0×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	115
Likely benign	4
Benign	8

Top pathogenic / likely-pathogenic (0)

SpliceAI

2482 predictions. Top by Δscore:

Variant	Effect	Δscore
7:100875563:C:A	acceptor_gain	1.0000
7:100875569:CCA:C	acceptor_loss	1.0000
7:100875571:A:AG	acceptor_gain	1.0000
7:100875571:A:AT	acceptor_loss	1.0000
7:100875572:G:A	acceptor_loss	1.0000
7:100875572:G:GG	acceptor_gain	1.0000
7:100875708:GACAG:G	donor_gain	1.0000
7:100875712:GGTG:G	donor_loss	1.0000
7:100875713:G:GA	donor_loss	1.0000
7:100875713:G:GG	donor_gain	1.0000
7:100881277:A:AG	acceptor_gain	1.0000
7:100881277:ACT:A	acceptor_gain	1.0000
7:100881278:C:G	acceptor_gain	1.0000
7:100881279:T:TA	acceptor_gain	1.0000
7:100881280:GCCAG:G	acceptor_loss	1.0000
7:100881281:CCA:C	acceptor_loss	1.0000
7:100881282:CAGA:C	acceptor_loss	1.0000
7:100881283:A:AG	acceptor_gain	1.0000
7:100881284:G:GA	acceptor_gain	1.0000
7:100881284:G:GT	acceptor_loss	1.0000
7:100881284:GA:G	acceptor_gain	1.0000
7:100881284:GAGA:G	acceptor_gain	1.0000
7:100881406:A:T	donor_gain	1.0000
7:100881409:GACTG:G	donor_gain	1.0000
7:100881414:G:GA	donor_loss	1.0000
7:100881414:G:GG	donor_gain	1.0000
7:100881415:T:G	donor_loss	1.0000
7:100882048:TCCAG:T	acceptor_loss	1.0000
7:100882051:AGGCT:A	acceptor_gain	1.0000
7:100882052:G:GA	acceptor_loss	1.0000

AlphaMissense

5811 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:100875628:G:C	R13T	1.000
7:100875628:G:T	R13M	1.000
7:100875629:G:C	R13S	1.000
7:100875629:G:T	R13S	1.000
7:100875630:G:C	D14H	1.000
7:100875633:A:G	K15E	1.000
7:100875636:T:C	F16L	1.000
7:100875637:T:C	F16S	1.000
7:100875637:T:G	F16C	1.000
7:100875638:C:A	F16L	1.000
7:100875638:C:G	F16L	1.000
7:100875645:G:A	E19K	1.000
7:100875648:C:A	R20S	1.000
7:100875648:C:T	R20C	1.000
7:100881397:C:A	R79S	1.000
7:100881404:G:C	R81T	1.000
7:100881404:G:T	R81M	1.000
7:100881405:G:C	R81S	1.000
7:100881405:G:T	R81S	1.000
7:100882117:T:C	F155L	1.000
7:100882118:T:C	F155S	1.000
7:100882119:T:A	F155L	1.000
7:100882119:T:G	F155L	1.000
7:100882121:T:C	L156P	1.000
7:100882156:G:C	A168P	1.000
7:100882160:T:A	V169D	1.000
7:100882168:T:G	Y172D	1.000
7:100882182:G:C	K176N	1.000
7:100882182:G:T	K176N	1.000
7:100882216:T:C	F188L	1.000

dbSNP variants (sampled 300 via entrez): RS1000487700 (7:100879015 C>T), RS1000793942 (7:100876624 C>G,T), RS1001214408 (7:100885554 T>C), RS1001462526 (7:100888307 G>GC), RS1001618762 (7:100875302 G>C,T), RS1001949384 (7:100876357 G>T), RS1002048627 (7:100888560 G>A,C), RS1002144505 (7:100881606 C>A,G), RS1002214142 (7:100880368 T>C), RS1002312414 (7:100878988 C>G,T), RS1002401040 (7:100874668 G>A), RS1002817909 (7:100886924 A>C,G), RS1002891389 (7:100886761 T>G), RS1002902419 (7:100877999 A>C,G), RS1002919506 (7:100887282 C>T)

Disease associations

OMIM: gene MIM:614469 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST001684_4	Plasminogen activator inhibitor type 1 levels (PAI-1)	6.000000e-13
GCST003818_36	Resting heart rate	1.000000e-41
GCST005845_4	Heart rate increase in response to exercise	3.000000e-16
GCST005846_7	Heart rate response to recovery post exercise (10 sec)	6.000000e-21
GCST005847_9	Heart rate response to recovery post exercise (20 sec)	3.000000e-21
GCST005848_15	Heart rate response to recovery post exercise (50 sec)	4.000000e-23
GCST005849_14	Heart rate response to recovery post exercise (40 sec)	6.000000e-24
GCST005850_6	Heart rate response to recovery post exercise (30 sec)	8.000000e-23
GCST007217_2	RR interval (heart rate)	7.000000e-11
GCST007250_7	Nonunion in individuals with fractures	3.000000e-07
GCST008103_164	Bipolar disorder	7.000000e-06
GCST010083_136	Hemoglobin levels	1.000000e-09
GCST90013406_116	Liver enzyme levels (alkaline phosphatase)	3.000000e-15

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004792	plasminogen activator inhibitor 1 measurement
EFO:0009184	heart rate response to exercise
EFO:0009185	heart rate response to recovery post exercise
EFO:0004831	RR interval
EFO:0009707	fractures, ununited
EFO:0004509	hemoglobin measurement
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067251 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.95	Kd	1131	nM	CHEMBL3752910
5.95	ED50	1131	nM	CHEMBL3752910
5.89	Kd	1288	nM	CHEMBL5653589
5.89	ED50	1288	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149489: Binding affinity to human SRRT incubated for 45 mins by Kinobead based pull down assay	kd	1.1308	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149489: Binding affinity to human SRRT incubated for 45 mins by Kinobead based pull down assay	kd	1.2878	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases reaction, increases expression, decreases expression, increases abundance	6
Benzo(a)pyrene	increases expression, increases methylation	3
Valproic Acid	affects expression, decreases expression, increases expression, increases methylation	3
bisphenol A	decreases expression	2
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	2
Lead	decreases expression, affects expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
geldanamycin	increases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
tetramethylpyrazine	decreases reaction, increases expression	1
tetrabromobisphenol A	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
coumarin	affects phosphorylation	1
enzacamene	increases expression, increases reaction	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
SB 203580	decreases reaction, increases expression	1
U 0126	decreases reaction, increases expression	1
pyrazolanthrone	decreases reaction, increases expression	1
3-(4-methylphenylsulfonyl)-2-propenenitrile	decreases reaction, increases expression	1
4(2’-aminoethyl)amino-1,8-dimethylimidazo(1,2-a)quinoxaline	decreases reaction, increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol B	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652531	Binding	Binding affinity to human SRRT incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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