SYNCRIP

Summary

SYNCRIP (synaptotagmin binding cytoplasmic RNA interacting protein, HGNC:16918) is a protein-coding gene on chromosome 6q14.3, encoding Heterogeneous nuclear ribonucleoprotein Q (O60506). Heterogenous nuclear ribonucleoprotein (hnRNP) implicated in mRNA processing mechanisms. It is a selective cancer dependency (DepMap: 26.4% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a member of the cellular heterogeneous nuclear ribonucleoprotein (hnRNP) family. hnRNPs are RNA binding proteins that complex with heterogeneous nuclear RNA (hnRNA) and regulate alternative splicing, polyadenylation, and other aspects of mRNA metabolism and transport. The encoded protein plays a role in multiple aspects of mRNA maturation and is associated with several multiprotein complexes including the apoB RNA editing-complex and survival of motor neurons (SMN) complex. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the short arm of chromosome 20.

Source: NCBI Gene 10492 — RefSeq curated summary.

At a glance

• Gene–disease (curated): SYNCRIP-related neurodevelopmental disorder (Definitive, ClinGen) — +1 more curated relationship
• Clinical variants (ClinVar): 143 total — 4 pathogenic, 3 likely-pathogenic
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 26.4% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_006372

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16918
Approved symbol	SYNCRIP
Name	synaptotagmin binding cytoplasmic RNA interacting protein
Location	6q14.3
Locus type	gene with protein product
Status	Approved
Aliases	NSAP1, GRY-RBP, dJ3J17.2, HNRPQ1, hnRNP-Q, HNRNPQ
Ensembl gene	ENSG00000135316
Ensembl biotype	protein_coding
OMIM	616686
Entrez	10492

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 19 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000355238, ENST00000369622, ENST00000444272, ENST00000616122, ENST00000676542, ENST00000676630, ENST00000676637, ENST00000676688, ENST00000677059, ENST00000677481, ENST00000677514, ENST00000677646, ENST00000677771, ENST00000678355, ENST00000678528, ENST00000678589, ENST00000678618, ENST00000678816, ENST00000678878, ENST00000678899, ENST00000678930, ENST00000710383

RefSeq mRNA: 8 — MANE Select: NM_006372 NM_001159673, NM_001159674, NM_001159675, NM_001159676, NM_001159677, NM_001253771, NM_001410938, NM_006372

CCDS: CCDS5005, CCDS55041, CCDS75491, CCDS93965, CCDS93966, CCDS93967

Canonical transcript exons

ENST00000369622 — 11 exons

Exon	Start	End
ENSE00000760231	85618818	85618939
ENSE00000760232	85619268	85619417
ENSE00000798133	85623977	85624112
ENSE00000798135	85636967	85637143
ENSE00000798137	85637243	85637356
ENSE00000798138	85640221	85640328
ENSE00000798141	85640446	85640564
ENSE00001450462	85641292	85641451
ENSE00001827916	85613976	85615347
ENSE00001840554	85642797	85642886
ENSE00001885760	85622482	85622687

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 98.29.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 50.9609 / max 930.7114, expressed in 1823 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
74609	17.9052	1768
74607	14.4917	1778
74606	10.2377	1726
74611	6.9986	1710
74610	0.7304	392
74608	0.5370	313
74612	0.0602	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	98.29	gold quality
ganglionic eminence	UBERON:0004023	98.03	gold quality
amniotic fluid	UBERON:0000173	97.34	gold quality
upper leg skin	UBERON:0004262	97.27	gold quality
skin of hip	UBERON:0001554	97.23	gold quality
tendon of biceps brachii	UBERON:0008188	97.18	gold quality
embryo	UBERON:0000922	97.15	gold quality
sperm	CL:0000019	96.86	gold quality
cortical plate	UBERON:0005343	96.85	gold quality
stromal cell of endometrium	CL:0002255	96.77	gold quality
secondary oocyte	CL:0000655	96.76	gold quality
cauda epididymis	UBERON:0004360	96.71	gold quality
tendon	UBERON:0000043	96.64	gold quality
endometrium	UBERON:0001295	96.64	gold quality
vermiform appendix	UBERON:0001154	96.48	gold quality
islet of Langerhans	UBERON:0000006	96.42	gold quality
rectum	UBERON:0001052	96.39	gold quality
cervix squamous epithelium	UBERON:0006922	96.34	gold quality
endothelial cell	CL:0000115	96.27	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.25	gold quality
monocyte	CL:0000576	96.14	gold quality
tonsil	UBERON:0002372	96.11	gold quality
blood vessel layer	UBERON:0004797	96.08	gold quality
calcaneal tendon	UBERON:0003701	96.04	gold quality
mononuclear cell	CL:0000842	96.01	gold quality
colonic epithelium	UBERON:0000397	95.96	gold quality
leukocyte	CL:0000738	95.95	gold quality
esophagus squamous epithelium	UBERON:0006920	95.95	gold quality
caecum	UBERON:0001153	95.93	gold quality
biceps brachii	UBERON:0001507	95.91	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6379	no	1585.12
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

29 targeting SYNCRIP, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-1284	99.67	73.56	1353
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-148A-5P	99.30	68.27	1141
HSA-MIR-548AS-3P	99.12	69.12	2294
HSA-MIR-3168	99.08	67.75	1384
HSA-MIR-5094	98.63	67.11	1062
HSA-MIR-3192-3P	98.62	65.80	970
HSA-MIR-4662A-5P	98.48	67.18	1007
HSA-MIR-3166	98.24	66.63	1223
HSA-MIR-6807-5P	97.51	64.25	1046
HSA-MIR-4445-5P	97.21	66.16	832
HSA-MIR-4714-3P	96.53	67.44	452
HSA-MIR-548AD-3P	94.39	66.04	350
HSA-MIR-6774-3P	89.14	65.20	68

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 26.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 24)

• The overexpression of NSAP1 specifically enhanced HCV IRES-dependent translation, and knockdown of NSAP1 by use of a small interfering RNA specifically inhibited the translation of HCV mRNA. (PMID:15340051)
• SYNCRIP is transported within the dendrite as a component of mRNA granules (PMID:15475564)
• methylation of hnRNPQ is important for its nuclear localization (PMID:16765914)
• Results suggest hnRNPQ interacts via its acidic domain (AcD) with Apobec1 and that this interaction is regulated by AcD phosphorylation. (PMID:17010310)
• Data demonstrate that hnRNP Q is a splicing modulator of SMN2, further underscoring the potential of hnRNP Q as a therapeutic target for spinal muscular atrophy. (PMID:18794368)
• Results demonstrate that galectin-3 stabilizes hnRNP Q via complex formation, and reduction in the hnRNP Q level leads to slow proliferation and less susceptibility to 5-FU. (PMID:19137262)
• SYNCRIP participates in both RNA replication and translation in HCV life cycle. (PMID:19232660)
• Data demonstrate that expression levels of hnRNP A1, Q, K, R, and U influence HIV-1 production by persistently infected (PMID:19808671)
• These data indicate that hnRNP Q can stimulate the protein production of HIV-1 Rev-dependent mRNAs without changing mRNA levels and mRNA export, respectively. (PMID:23679954)
• The hnRNP Q is a novel substrate of SHP2 and the SHP2 activity may be also involved in RNA metabolisms via dephosphorylation of hnRNP Q. (PMID:23946508)
• The inhibitory effect of hnRNP Q on YB-1 mRNA translation can be explained by its ability to pro-mote YB-1 binding to the regulatory element within the YB-1 mRNA 3’ UTR. (PMID:23980891)
• hnRNPQ6 is required for APOBEC1-enhanced IL8 production. (PMID:25100733)
• The acidic domain is a unique structural feature of the splicing factor SYNCRIP. (PMID:27081926)
• our data indicate that hnRNP Q1 is a novel trans-acting factor that binds to Aurora-A mRNA 5’-UTRs and regulates its translation, which increases cell proliferation and contributes to tumorigenesis in colorectal cancer (PMID:28079881)
• SYNCRIP is required for survival of leukemia cells. SYNCRIP controls the myeloid leukemia stem cell program. (PMID:28436985)
• A cryptic RNA-binding domain mediates Syncrip recognition and exosomal partitioning of miRNA targets. (PMID:29483512)
• The EGF/hnRNP Q1-induced translation of Aurora-A mRNA is mediated by the mTOR and ERK pathways. (PMID:29884818)
• Results indentified two candidate haploinsufficient genes contiguous at 6q14 SYNCRIP (encoding hnRNP-Q) and SNHG5 (that hosts snoRNAs), both involved in regulating RNA maturation and translation inT-cell acute lymphoblastic leukemia (T-ALL). (PMID:30266814)
• Identification of the frequent presence of hnRNP R and hnRNP Q in frontotemporal lobar degeneration (FTLD)-FUS inclusions suggests a potential role for these hnRNPs in FTLD-FUS pathogenesis and supports the role of dysfunctional RNA metabolism in FTLD. (PMID:30755280)
• ATP binds nucleic-acid-binding domains beyond RRM fold. (PMID:31791586)
• the terminal loop of pri-let-7a was shown to be the main contributor for its interaction with SYNCRIP. Functional studies demonstrated that the SYNCRIP RRM2-3 domain can promote the processing of pri-let-7a (PMID:31907208)
• A novel antisense lncRNA NT5E promotes progression by modulating the expression of SYNCRIP and predicts a poor prognosis in pancreatic cancer. (PMID:32770626)
• Further evidence for de novo variants in SYNCRIP as the cause of a neurodevelopmental disorder. (PMID:34157790)
• Oculopharyngeal muscular dystrophy mutations link the RNA-binding protein HNRNPQ to autophagosome biogenesis. (PMID:37559347)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	syncripl	ENSDARG00000026723
danio_rerio	syncrip	ENSDARG00000040184
mus_musculus	Syncrip	ENSMUSG00000032423
rattus_norvegicus	Syncrip	ENSRNOG00000000204

Paralogs (24): ELAVL1 (ENSG00000066044), PABPC1 (ENSG00000070756), RBMS2 (ENSG00000076067), PABPC4 (ENSG00000090621), PABPC1L (ENSG00000101104), ELAVL2 (ENSG00000107105), RBM24 (ENSG00000112183), TARDBP (ENSG00000120948), HNRNPR (ENSG00000125944), RBM38 (ENSG00000132819), SF3B4 (ENSG00000143368), RBMS3 (ENSG00000144642), PABPC3 (ENSG00000151846), RBMS1 (ENSG00000153250), RBM45 (ENSG00000155636), ELAVL4 (ENSG00000162374), PABPC5 (ENSG00000174740), PUF60 (ENSG00000179950), PABPC1L2B (ENSG00000184388), PABPC1L2A (ENSG00000186288), RBM34 (ENSG00000188739), ELAVL3 (ENSG00000196361), RBM14 (ENSG00000239306), PABPC4L (ENSG00000254535)

Protein

Protein identifiers

Heterogeneous nuclear ribonucleoprotein Q — O60506 (reviewed: O60506)

Alternative names: Glycine- and tyrosine-rich RNA-binding protein, NS1-associated protein 1, Synaptotagmin-binding, cytoplasmic RNA-interacting protein

All UniProt accessions (13): A0A7I2V2F0, O60506, A0A7I2V2F2, A0A7I2V309, A0A7I2V346, A0A7I2V4J0, A0A7I2V4Z0, A0A7I2V5Q6, A0A7I2YQN2, A0A7I2YQV8, A0AA34QW03, B7Z645, F6UXX1

UniProt curated annotations — full annotation on UniProt →

Function. Heterogenous nuclear ribonucleoprotein (hnRNP) implicated in mRNA processing mechanisms. Component of the CRD-mediated complex that promotes MYC mRNA stability. Isoform 1, isoform 2 and isoform 3 are associated in vitro with pre-mRNA, splicing intermediates and mature mRNA protein complexes. Isoform 1 binds to apoB mRNA AU-rich sequences. Isoform 1 is part of the APOB mRNA editosome complex and may modulate the postranscriptional C to U RNA-editing of the APOB mRNA through either by binding to A1CF (APOBEC1 complementation factor), to APOBEC1 or to RNA itself. May be involved in translationally coupled mRNA turnover. Implicated with other RNA-binding proteins in the cytoplasmic deadenylation/translational and decay interplay of the FOS mRNA mediated by the major coding-region determinant of instability (mCRD) domain. Interacts in vitro preferentially with poly(A) and poly(U) RNA sequences. Isoform 3 may be involved in cytoplasmic vesicle-based mRNA transport through interaction with synaptotagmins. Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. Upon interferon-gamma activation assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3’-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation; does not seem to be essential for GAIT complex function.

Subunit / interactions. Isoform 1 is a component of the APOB mRNA editosome complex and interacts with APOBEC1 and A1CF (APOBEC1 complementation factor). Part of a complex associated with the FOS mCRD domain and consisting of PABPC1, PAIP1, CSDE1/UNR, HNRPD and SYNCRIP. Isoform 3 interacts with HNRPR. Interacts with POLR2A hyperphosphorylated C-terminal domain. Isoform 1, isoform 2 and isoform 3 interact with SMN. Isoform 3 interacts through its C-terminal domain with SYT7, SYT8 and SYT9. The non-phosphorylated and phosphorylated forms are colocalized with PAIP1 in polysomes. Interacts with HABP4. Identified in a histone pre-mRNA complex, at least composed of ERI1, LSM11, SLBP, SNRPB, SYNCRIP and YBX1. Identified in the spliceosome C complex. Component of the coding region determinant (CRD)-mediated complex, composed of DHX9, HNRNPU, IGF2BP1, SYNCRIP and YBX1. Identified in a mRNP complex, at least composed of DHX9, DDX3X, ELAVL1, HNRNPU, IGF2BP1, ILF3, PABPC1, PCBP2, PTBP2, STAU1, STAU2, SYNCRIP and YBX1. Identified in a mRNP granule complex, at least composed of ACTB, ACTN4, DHX9, ERG, HNRNPA1, HNRNPA2B1, HNRNPAB, HNRNPD, HNRNPL, HNRNPR, HNRNPU, HSPA1, HSPA8, IGF2BP1, ILF2, ILF3, NCBP1, NCL, PABPC1, PABPC4, PABPN1, RPLP0, RPS3, RPS3A, RPS4X, RPS8, RPS9, SYNCRIP, YBX1 and untranslated mRNAs. Interacts with GTPBP1. Component of the GAIT complex; in humans the complex assembly seems to be a two-step process in which EPRS1 first associates with SYNCRIP to form a pre-GAIT complex which is deficient in GAIT element binding. (Microbial infection) Interacts with minute virus of mice (MVM) NS1 protein. (Microbial infection) Interacts with herpes virus 8/HHV-8 protein vIRF-1; this interaction induces ubiquitination and degradation of SYNCRIP.

Subcellular location. Cytoplasm. Microsome. Endoplasmic reticulum. Nucleus Nucleus. Nucleoplasm Nucleus. Nucleoplasm.

Tissue specificity. Ubiquitously expressed. Detected in heart, brain, pancreas, placenta, spleen, lung, liver, skeletal muscle, kidney, thymus, prostate, uterus, small intestine, colon, peripheral blood and testis.

Post-translational modifications. Phosphorylated on tyrosine. The membrane-bound form found in microsomes is phosphorylated in vitro by insulin receptor tyrosine kinase (INSR). Phosphorylation is inhibited upon binding to RNA, whereas the cytoplasmic form is poorly phosphorylated.

Domain organisation. The domain containing eight Arg-Gly-Gly repeats (RGG/RXR-box) may be involved in RNA-binding and protein-protein interactions. It is methylated by PRMT1, and essential for nuclear localization.

Miscellaneous. May be due to a competing donor splice site. May be due to a competing donor splice site and to an exon inclusion. May be due to a competing donor splice site and to an exon inclusion. May be due to a competing donor splice site and to an exon inclusion.

Isoforms (5)

UniProt ID	Names	Canonical?
O60506-1	1, hnRNP Q3	yes
O60506-2	2, hnRNP Q2
O60506-3	3, hnRNP Q1
O60506-4	4
O60506-5	5

RefSeq proteins (8): NP_001153145, NP_001153146, NP_001153147, NP_001153148, NP_001153149, NP_001240700, NP_001397867, NP_006363* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR006535	HnRNP_R/Q_splicing_fac	Family
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR034544	hnRNPQ_RRM1	Domain
IPR034548	hnRNPQ_RRM2	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR041337	hnRNP_Q_AcD	Domain

Pfam: PF00076, PF18360

UniProt features (74 total): modified residue 18, repeat 11, helix 10, strand 9, region of interest 5, compositionally biased region 4, splice variant 4, sequence conflict 4, domain 3, cross-link 2, initiator methionine 1, chain 1, short sequence motif 1, turn 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
6KOR	X-RAY DIFFRACTION	2.6
2DGU	SOLUTION NMR
2MXT	SOLUTION NMR
2NBB	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60506-F1	70.83	0.40

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 (20): 2, 159, 221, 363, 373, 444, 444, 496, 510, 518, 518, 526, 526, 536, 536, 539, 539, 587, 168, 607

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 437 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, GOBP_CYTOPLASMIC_TRANSLATION, RNGTGGGC_UNKNOWN, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, MODULE_52, RRAGTTGT_UNKNOWN, MORF_SMC1L1, PAX4_01, E2F4DP1_01, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_RESPONSE_TO_PEPTIDE, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, YANG_BREAST_CANCER_ESR1_LASER_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS

GO Biological Process (14): mRNA splicing, via spliceosome (GO:0000398), osteoblast differentiation (GO:0001649), RNA processing (GO:0006396), RNA splicing (GO:0008380), mRNA modification (GO:0016556), negative regulation of translation (GO:0017148), CRD-mediated mRNA stabilization (GO:0070934), cellular response to type II interferon (GO:0071346), chromosomal 5-methylcytosine DNA demethylation pathway (GO:0141166), negative regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay (GO:1900152), negative regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay (GO:2000623), positive regulation of cytoplasmic translation (GO:2000767), mRNA processing (GO:0006397), regulation of translation (GO:0006417)

GO Molecular Function (4): RNA binding (GO:0003723), mRNA 5’-UTR binding (GO:0048027), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (14): nucleus (GO:0005634), nucleoplasm (GO:0005654), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), membrane (GO:0016020), mRNA editing complex (GO:0045293), CRD-mediated mRNA stability complex (GO:0070937), catalytic step 2 spliceosome (GO:0071013), histone pre-mRNA 3’end processing complex (GO:0071204), GAIT complex (GO:0097452), mCRD-mediated mRNA stability complex (GO:0106002), ribonucleoprotein complex (GO:1990904), spliceosomal complex (GO:0005681), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein-containing complex	3
RNA processing	2
mRNA metabolic process	2
translation	2
negative regulation of mRNA catabolic process	2
binding	2
intracellular membrane-bounded organelle	2
cytoplasm	2
catalytic complex	2
nuclear protein-containing complex	2
ribonucleoprotein complex	2
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
ossification	1
cell differentiation	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
RNA modification	1
regulation of translation	1
negative regulation of gene expression	1
negative regulation of protein metabolic process	1
mRNA stabilization	1
response to type II interferon	1
cellular response to cytokine stimulus	1
DNA metabolic process	1
nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	1
regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	1
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	1
regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	1
cytoplasmic translation	1
positive regulation of translation	1
regulation of cytoplasmic translation	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
nucleic acid binding	1
mRNA binding	1
nuclear lumen	1
endomembrane system	1

Protein interactions and networks

STRING

2820 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SYNCRIP	RPL13A	P40429	996
SYNCRIP	EPRS1	P07814	995
SYNCRIP	GAPDH	P00354	991
SYNCRIP	MRPL13	Q9BYD1	971
SYNCRIP	PAIP1	Q9H074	961
SYNCRIP	YBX1	P16990	917
SYNCRIP	HNRNPU	Q00839	909
SYNCRIP	DHX9	Q08211	905
SYNCRIP	HNRNPD	P07029	825
SYNCRIP	SMN1	Q16637	814
SYNCRIP	CSDE1	O75534	812
SYNCRIP	ERI1	Q8IV48	784
SYNCRIP	HNRNPC	P07910	776
SYNCRIP	GEMIN2	O14893	714
SYNCRIP	EIF4G1	Q04637	714

IntAct

309 interactions, top by confidence:

A	B	Type	Score
HNRNPC	KPNA3	psi-mi:“MI:0914”(association)	0.850
SYNCRIP	PRMT8	psi-mi:“MI:0915”(physical association)	0.830
PRMT8	SYNCRIP	psi-mi:“MI:0915”(physical association)	0.830
YBX1	HNRNPR	psi-mi:“MI:0914”(association)	0.770
N	HNRNPR	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
IGF2BP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
EPRS1	SYNCRIP	psi-mi:“MI:0915”(physical association)	0.640
EPRS1	SYNCRIP	psi-mi:“MI:0914”(association)	0.640
IGF2BP1	SYNCRIP	psi-mi:“MI:0914”(association)	0.580
IGF2BP1	SYNCRIP	psi-mi:“MI:0403”(colocalization)	0.580
SYNCRIP	PRMT8	psi-mi:“MI:0915”(physical association)	0.560
PRMT8	SYNCRIP	psi-mi:“MI:0915”(physical association)	0.560
CHEK2	PPM1G	psi-mi:“MI:0914”(association)	0.560
HNRNPD	HNRNPDL	psi-mi:“MI:0914”(association)	0.560
HNRNPH2	PLOD2	psi-mi:“MI:0914”(association)	0.530
N	RBM47	psi-mi:“MI:0914”(association)	0.530
RPS3	ZNF316	psi-mi:“MI:0914”(association)	0.530
ELAVL2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
YPEL5	SYNCRIP	psi-mi:“MI:0914”(association)	0.510
KIF1C	KIF1B	psi-mi:“MI:2364”(proximity)	0.480
CPSF6	DDX39A	psi-mi:“MI:0914”(association)	0.480
ESR1		psi-mi:“MI:0914”(association)	0.460
RBM45	HNRNPDL	psi-mi:“MI:0914”(association)	0.460
	SYNCRIP	psi-mi:“MI:0915”(physical association)	0.400
PKD1L2	SYNCRIP	psi-mi:“MI:0915”(physical association)	0.400
TOR1AIP1	SYNCRIP	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (950): SYNCRIP (Affinity Capture-MS), PRMT8 (Two-hybrid), SYNCRIP (Two-hybrid), SYNCRIP (Affinity Capture-MS), SYNCRIP (Affinity Capture-MS), SYNCRIP (Affinity Capture-MS), SYNCRIP (Affinity Capture-MS), SYNCRIP (Affinity Capture-MS), SYNCRIP (Affinity Capture-MS), SYNCRIP (Reconstituted Complex), SYNCRIP (Affinity Capture-MS), SYNCRIP (Affinity Capture-MS), SYNCRIP (Affinity Capture-MS), SYNCRIP (Affinity Capture-Western), DDX17 (Co-fractionation)

ESM2 similar proteins: A0A8M1NHK4, A0AV96, O22173, O60506, P11940, P21187, P29341, P61286, Q13310, Q15233, Q1LZD9, Q32NN2, Q4KLH4, Q4R4J1, Q4V7D7, Q5R469, Q5R5P4, Q5R8F7, Q5R9H4, Q5RFL9, Q5W9D5, Q5W9D6, Q5W9D7, Q5YD48, Q5ZM16, Q66H68, Q6DEY7, Q6GR16, Q6IP09, Q6IRN2, Q6P0D0, Q7JJZ8, Q7TMK9, Q7TP47, Q8BHS3, Q8R326, Q8WXF1, Q91WT8, Q91XU1, Q923K9

Diamond homologs: A0A8M1NHK4, A0AV96, A0JM51, A4FV72, A4QUF0, A8WLV5, O01671, O04425, O43040, O43390, O60506, P28659, P33240, P86049, Q08BH5, Q08E07, Q0P4R6, Q0V9L3, Q10B98, Q14498, Q28HE9, Q2HJG2, Q2UK72, Q3UEB3, Q4QQT3, Q4R2Z0, Q4R535, Q5B630, Q5EA36, Q5R469, Q5R5P4, Q5R723, Q5R9H4, Q5RC41, Q5RC80, Q5RDA3, Q5SZQ8, Q5YD48, Q66H68, Q6DCB7

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SYNCRIP	“form complex”	“C-to-U editosome complex”	binding
FGFR1	down-regulates	SYNCRIP	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 201 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
mRNA Polyadenylation	24	14.2×	1e-18
Processing of Capped Intron-Containing Pre-mRNA	21	11.7×	1e-14
mRNA Splicing - Major Pathway	26	9.6×	4e-16
RNA Polymerase II Transcription Termination	6	8.9×	4e-03
snRNP Assembly	6	8.6×	4e-03
Dengue Virus-Host Interactions	23	7.1×	2e-11
mRNA Splicing	9	6.7×	6e-04
CHD1 and CHD2 subfamily	8	5.9×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of cytoplasmic translation	8	43.8×	1e-09
mRNA stabilization	10	20.2×	1e-08
spliceosomal snRNP assembly	5	16.1×	1e-03
regulation of alternative mRNA splicing, via spliceosome	10	13.5×	4e-07
negative regulation of translation	11	11.9×	3e-07
translational initiation	6	11.9×	1e-03
mRNA export from nucleus	7	11.4×	2e-04
mRNA splicing, via spliceosome	20	10.1×	8e-12

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	3
Uncertain significance	94
Likely benign	11
Benign	1

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
150937	GRCh38/hg38 6q13-24.1(chr6:74382807-142040500)x3	Pathogenic
4056885	NM_006372.5(SYNCRIP):c.1336C>T (p.Arg446Ter)	Pathogenic
4075486	NM_006372.5(SYNCRIP):c.700_701del (p.Ile234fs)	Pathogenic
4532038	NM_006372.5(SYNCRIP):c.1473dup (p.Gln492fs)	Pathogenic
2576614	NM_006372.5(SYNCRIP):c.438dup (p.Pro147fs)	Likely pathogenic
3067816	GRCh37/hg19 6q14.3(chr6:86322600-86329135)x1	Likely pathogenic
987161	NM_006372.5(SYNCRIP):c.858_859del (p.Gly287fs)	Likely pathogenic

SpliceAI

2081 predictions. Top by Δscore:

Variant	Effect	Δscore
6:85615008:T:TA	donor_gain	1.0000
6:85615343:CATAC:C	acceptor_gain	1.0000
6:85615344:ATAC:A	acceptor_gain	1.0000
6:85615345:TAC:T	acceptor_gain	1.0000
6:85615345:TACC:T	acceptor_loss	1.0000
6:85615346:AC:A	acceptor_gain	1.0000
6:85615346:ACC:A	acceptor_loss	1.0000
6:85615347:CCTAT:C	acceptor_gain	1.0000
6:85615348:C:A	acceptor_loss	1.0000
6:85615348:C:CC	acceptor_gain	1.0000
6:85615349:T:A	acceptor_loss	1.0000
6:85615351:T:C	acceptor_gain	1.0000
6:85615351:T:TC	acceptor_gain	1.0000
6:85618814:T:TC	donor_loss	1.0000
6:85618815:C:CC	donor_loss	1.0000
6:85618816:A:AC	donor_gain	1.0000
6:85618816:A:AG	donor_loss	1.0000
6:85618817:C:CT	donor_gain	1.0000
6:85618817:CA:C	donor_gain	1.0000
6:85618817:CAT:C	donor_gain	1.0000
6:85618817:CATT:C	donor_gain	1.0000
6:85618817:CATTT:C	donor_gain	1.0000
6:85618937:AGCC:A	acceptor_loss	1.0000
6:85618939:CCT:C	acceptor_gain	1.0000
6:85618939:CCTTA:C	acceptor_loss	1.0000
6:85618940:C:CC	acceptor_gain	1.0000
6:85618940:C:T	acceptor_gain	1.0000
6:85618940:CTTAA:C	acceptor_loss	1.0000
6:85618941:T:C	acceptor_gain	1.0000
6:85619263:TTTAC:T	donor_loss	1.0000

AlphaMissense

4081 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:85614935:G:T	R565S	1.000
6:85618875:G:T	P408Q	1.000
6:85618877:C:A	K407N	1.000
6:85618877:C:G	K407N	1.000
6:85618879:T:C	K407E	1.000
6:85618881:G:T	A406D	1.000
6:85619275:G:T	A384D	1.000
6:85619297:G:C	H377D	1.000
6:85619301:G:C	F375L	1.000
6:85619301:G:T	F375L	1.000
6:85619302:A:C	F375C	1.000
6:85619302:A:G	F375S	1.000
6:85619303:A:C	F375V	1.000
6:85619303:A:G	F375L	1.000
6:85619303:A:T	F375I	1.000
6:85619305:G:T	A374E	1.000
6:85619306:C:G	A374P	1.000
6:85619309:A:G	Y373H	1.000
6:85619322:C:A	K368N	1.000
6:85619322:C:G	K368N	1.000
6:85619329:C:G	R366P	1.000
6:85619392:A:G	L345P	1.000
6:85619392:A:T	L345H	1.000
6:85619398:C:G	R343P	1.000
6:85619399:G:T	R343S	1.000
6:85619401:A:T	V342E	1.000
6:85619403:A:C	F341L	1.000
6:85619403:A:T	F341L	1.000
6:85619404:A:C	F341C	1.000
6:85619404:A:G	F341S	1.000

dbSNP variants (sampled 300 via entrez): RS1000017778 (6:85632213 T>A,C), RS1000031201 (6:85637901 T>C), RS1000033818 (6:85624262 C>G,T), RS1000111392 (6:85634652 C>T), RS1000149635 (6:85629838 G>A,C), RS1000207575 (6:85627504 ACT>A), RS1000225021 (6:85642448 C>A,G,T), RS1000226356 (6:85634460 C>T), RS1000392143 (6:85612021 A>G), RS1000444183 (6:85618364 A>G), RS1000449579 (6:85637565 A>T), RS1000504218 (6:85629659 T>C), RS1000656268 (6:85623768 C>A,T), RS1000679614 (6:85638845 A>T), RS1000742057 (6:85639815 G>A)

Disease associations

OMIM: gene MIM:616686 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Strong	Autosomal dominant
SYNCRIP-related neurodevelopmental disorder	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
SYNCRIP-related neurodevelopmental disorder	Definitive	AD

Mondo (3): SYNCRIP-related neurodevelopmental disorder (MONDO:0800456), neurodevelopmental disorder (MONDO:0700092), autism spectrum disorder (MONDO:0005258)

Orphanet (1): NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295997 (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
7.65	Kd	22.5	nM	CHEMBL3752910
7.65	ED50	22.5	nM	CHEMBL3752910
6.53	Kd	295.8	nM	CHEMBL5653589
6.53	ED50	295.8	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 11 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	2149533: Binding affinity to human SYNCRIP incubated for 45 mins by Kinobead based pull down assay	kd	0.0225	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149533: Binding affinity to human SYNCRIP incubated for 45 mins by Kinobead based pull down assay	kd	0.2958	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, affects expression, decreases expression	8
methylmercuric chloride	increases expression, affects cotreatment	4
bisphenol A	decreases expression, decreases methylation, increases expression	4
trichostatin A	affects expression, affects cotreatment, decreases expression, increases expression	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	3
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, decreases expression	3
cobaltous chloride	decreases expression	2
Vorinostat	decreases expression	2
Benzo(a)pyrene	decreases expression	2
Cadmium	increases abundance, increases palmitoylation, decreases expression, decreases reaction	2
Nickel	increases expression	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
Tobacco Smoke Pollution	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
TAK-243	decreases sumoylation	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
kojic acid	increases expression	1
arsenite	affects localization	1
methylparaben	decreases expression	1
sodium arsenite	decreases expression	1
2-bromopalmitate	increases abundance, increases palmitoylation, decreases reaction	1
beta-methylcholine	affects expression	1
cyclic 3’,5’-uridine monophosphate	affects binding	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	decreases expression	1
monomethylarsonous acid	decreases expression	1
K 7174	decreases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4119034	Binding	Binding affinity to SYNCRIP in human NCI-H358 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E2LC	HAP1 SYNCRIP (-) 2	Cancer cell line	Male
CVCL_XU05	HAP1 SYNCRIP (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder