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Center for Computational Systems Medicine
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Fusion Gene and Fusion Protein Summary

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Fusion Amino Acid Sequences (multiple BPs and multiple gene isoforms)

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Fusion Protein Breakpoint Sequences - (for the Screening of the FusionNeoAntigens)

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Potential FusionNeoAntigens in HLA I - (netMHCpan v4.1 + deepHLApan v1.1)

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Potential FusionNeoAntigens in HLA II - (netMHCIIpan v4.1)

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Fusion Breakpoint 14 AA Peptide Structure - (RoseTTAFold)

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D - (Glide)

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Vaccine Design for the FusionNeoAntigens (RNA/protein sequences)

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Potential target of CAR-T therapy development

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Information on the samples that have these potential fusion neoantigens

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Fusion Protein Targeting Drugs - (Manual Curation)

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Fusion Protein Related diseases - (Manual Curation)

Fusion Protein:CIC-ZFP57

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CIC-ZFP57
FusionPDB ID: 16804
FusionGDB2.0 ID: 16804
HgeneTgene
Gene symbol

CIC

ZFP57

Gene ID

23152

346171

Gene namecapicua transcriptional repressorZFP57 zinc finger protein
SynonymsMRD45C6orf40|TNDM1|ZNF698|bA145L22|bA145L22.2
Cytomap

19q13.2

6p22.1

Type of geneprotein-codingprotein-coding
Descriptionprotein capicua homologzinc finger protein 57 homologzfp-57zinc finger protein 698
Modification date2020031320200327
UniProtAcc

Q96RK0

Main function of 5'-partner protein: FUNCTION: Transcriptional repressor which plays a role in development of the central nervous system (CNS). In concert with ATXN1 and ATXN1L, involved in brain development. {ECO:0000250|UniProtKB:Q924A2}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000160740, ENST00000572681, 
ENST00000575354, ENST00000575839, 
ENST00000376881, ENST00000376883, 
ENST00000383628, ENST00000416974, 
ENST00000432222, ENST00000435906, 
ENST00000437216, ENST00000446005, 
ENST00000448114, ENST00000488757, 
ENST00000547542, ENST00000547911, 
ENST00000548001, ENST00000548337, 
ENST00000548574, ENST00000548769, 
ENST00000549167, ENST00000549312, 
ENST00000549501, ENST00000552809, 
ENST00000552898, ENST00000552987, 
ENST00000553137, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score13 X 12 X 6=9362 X 3 X 2=12
# samples 122
** MAII scorelog2(12/936*10)=-2.96347412397489
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(2/12*10)=0.736965594166206
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: CIC [Title/Abstract] AND ZFP57 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CIC [Title/Abstract] AND ZFP57 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CIC(42791392)-ZFP57(29641535), # samples:2
Anticipated loss of major functional domain due to fusion event.CIC-ZFP57 seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF.
CIC-ZFP57 seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF.
CIC-ZFP57 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF.
CIC-ZFP57 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF.
CIC-ZFP57 seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF.
CIC-ZFP57 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
CIC-ZFP57 seems lost the major protein functional domain in Hgene partner, which is a transcription factor due to the frame-shifted ORF.
CIC-ZFP57 seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor due to the frame-shifted ORF.
CIC-ZFP57 seems lost the major protein functional domain in Tgene partner, which is a epigenetic factor due to the frame-shifted ORF.
CIC-ZFP57 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
CIC-ZFP57 seems lost the major protein functional domain in Tgene partner, which is a transcription factor due to the frame-shifted ORF.
* DoF score (Degree of Frequency) = # partners X # break points X # cancer types
** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10)

check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID


check button Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr19:42791392/chr6:29641535)
- FGviewer provides the online visualization of the retention search of the protein functional features across DNA, RNA, protein, and pathological levels.
- How to search
1. Put your fusion gene symbol.
2. Press the tab key until there will be shown the breakpoint information filled.
4. Go down and press 'Search' tab twice.
4. Go down to have the hyperlink of the search result.
5. Click the hyperlink.
6. See the FGviewer result for your fusion gene.
FGviewer

check buttonRetention analysis results of each fusion partner protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features, are available here.

check buttonFusion gene breakpoints across CIC (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure

check buttonFusion gene breakpoints across ZFP57 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure


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Fusion Amino Acid Sequences


check buttonFusion information from ORFfinder translation from full-length transcript sequence from FusionPDB.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)
BP loci
(transcript)
Predicted start
(transcript)
Predicted stop
(transcript)
Seq length
(amino acids)
ENST00000572681CICchr1942791392+ENST00000376881ZFP57chr629641535-461432476832951075
ENST00000572681CICchr1942791392+ENST00000376883ZFP57chr629641535-452332476832951075
ENST00000160740CICchr1942791392+ENST00000376881ZFP57chr629641535-250411378302395521
ENST00000160740CICchr1942791392+ENST00000376883ZFP57chr629641535-241311378302395521
ENST00000575354CICchr1942791392+ENST00000376881ZFP57chr629641535-18594921851750521
ENST00000575354CICchr1942791392+ENST00000376883ZFP57chr629641535-17684921851750521

check buttonDeepORF prediction of the coding potential based on the fusion transcript sequence of in-frame fusion genes. DeepORF is a coding potential classifier based on convolutional neural network by comparing the real Ribo-seq data. If the no-coding score < 0.5 and coding score > 0.5, then the in-frame fusion transcript is predicted as being likely translated.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandNo-coding scoreCoding score
ENST00000572681ENST00000376881CICchr1942791392+ZFP57chr629641535-0.0037374360.9962625
ENST00000572681ENST00000376883CICchr1942791392+ZFP57chr629641535-0.0041275810.99587244
ENST00000160740ENST00000376881CICchr1942791392+ZFP57chr629641535-0.128885140.87111485
ENST00000160740ENST00000376883CICchr1942791392+ZFP57chr629641535-0.137219520.8627805
ENST00000575354ENST00000376881CICchr1942791392+ZFP57chr629641535-0.144912330.85508764
ENST00000575354ENST00000376883CICchr1942791392+ZFP57chr629641535-0.160950630.8390494

check button Predicted full-length fusion amino acid sequences. For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among all the predicted ones.

Get the fusion protein sequences from here.

Fusion protein sequence information is available in the fasta format.
>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

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Fusion Protein Breakpoint Sequences for CIC-ZFP57

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
CICchr1942791392ZFP57chr6296415351137103GWTVRQRVTMMMQGKKKELREQHPSL
CICchr1942791392ZFP57chr62964153532471060RLDSETESDHDDARQEERASRTTSQS
CICchr1942791392ZFP57chr629641535492103GWTVRQRVTMMMQGKKKELREQHPSL

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Potential FusionNeoAntigen Information of CIC-ZFP57 in HLA I

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.
CIC-ZFP57_42791392_29641535.msa

check button Potential FusionNeoAntigen Information
* We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5)
Fusion geneHchrHbpTgeneTchrTbpHLA IFusionNeoAntigen peptideBinding scoreImmunogenic scoreNeoantigen start (at BP 13)Neoantigen end (at BP 13)
CIC-ZFP57chr1942791392chr6296415351137HLA-B08:01MQGKKKEL0.99780.83721119
CIC-ZFP57chr1942791392chr6296415351137HLA-B08:01MMQGKKKEL0.99510.93211019
CIC-ZFP57chr1942791392chr6296415351137HLA-B08:09MMQGKKKEL0.9750.78991019
CIC-ZFP57chr1942791392chr6296415351137HLA-B08:01MMMQGKKKEL0.97570.9558919
CIC-ZFP57chr1942791392chr6296415351137HLA-B08:18MQGKKKEL0.99780.83721119
CIC-ZFP57chr1942791392chr6296415351137HLA-B08:18MMQGKKKEL0.99510.93211019
CIC-ZFP57chr1942791392chr6296415351137HLA-B08:12MMQGKKKEL0.71090.95091019
CIC-ZFP57chr1942791392chr6296415351137HLA-C07:04MMQGKKKEL0.52390.96981019
CIC-ZFP57chr1942791392chr6296415351137HLA-B08:18MMMQGKKKEL0.97570.9558919

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Potential FusionNeoAntigen Information of CIC-ZFP57 in HLA II

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.
CIC-ZFP57_42791392_29641535.msa

check button Potential FusionNeoAntigen Information
* We used NetMHCIIpan v4.1 (%rank<0.5).
Fusion geneHchrHbpTgeneTchrTbpHLA IIFusionNeoAntigen peptideNeoantigen start (at BP 13)Neoantigen end (at BP 13)
CIC-ZFP57chr1942791392chr6296415351137DRB1-1102TMMMQGKKKELREQH823
CIC-ZFP57chr1942791392chr6296415351137DRB1-1116TMMMQGKKKELREQH823
CIC-ZFP57chr1942791392chr6296415351137DRB1-1121TMMMQGKKKELREQH823
CIC-ZFP57chr1942791392chr6296415351137DRB1-1121VTMMMQGKKKELREQ722
CIC-ZFP57chr1942791392chr6296415351137DRB1-1136TMMMQGKKKELREQH823
CIC-ZFP57chr1942791392chr6296415351137DRB1-1155TMMMQGKKKELREQH823
CIC-ZFP57chr1942791392chr6296415351137DRB1-1165TMMMQGKKKELREQH823
CIC-ZFP57chr1942791392chr6296415351137DRB1-1170TMMMQGKKKELREQH823
CIC-ZFP57chr1942791392chr6296415351137DRB1-1170VTMMMQGKKKELREQ722
CIC-ZFP57chr1942791392chr6296415351137DRB1-1301TMMMQGKKKELREQH823
CIC-ZFP57chr1942791392chr6296415351137DRB1-1315TMMMQGKKKELREQH823
CIC-ZFP57chr1942791392chr6296415351137DRB1-1315VTMMMQGKKKELREQ722
CIC-ZFP57chr1942791392chr6296415351137DRB1-1320TMMMQGKKKELREQH823
CIC-ZFP57chr1942791392chr6296415351137DRB1-1322TMMMQGKKKELREQH823
CIC-ZFP57chr1942791392chr6296415351137DRB1-1327TMMMQGKKKELREQH823
CIC-ZFP57chr1942791392chr6296415351137DRB1-1327VTMMMQGKKKELREQ722
CIC-ZFP57chr1942791392chr6296415351137DRB1-1335TMMMQGKKKELREQH823
CIC-ZFP57chr1942791392chr6296415351137DRB1-1351TMMMQGKKKELREQH823
CIC-ZFP57chr1942791392chr6296415351137DRB1-1352TMMMQGKKKELREQH823
CIC-ZFP57chr1942791392chr6296415351137DRB1-1357TMMMQGKKKELREQH823
CIC-ZFP57chr1942791392chr6296415351137DRB1-1357VTMMMQGKKKELREQ722
CIC-ZFP57chr1942791392chr6296415351137DRB1-1359TMMMQGKKKELREQH823
CIC-ZFP57chr1942791392chr6296415351137DRB1-1361TMMMQGKKKELREQH823
CIC-ZFP57chr1942791392chr6296415351137DRB1-1364TMMMQGKKKELREQH823
CIC-ZFP57chr1942791392chr6296415351137DRB1-1368TMMMQGKKKELREQH823
CIC-ZFP57chr1942791392chr6296415351137DRB1-1369TMMMQGKKKELREQH823
CIC-ZFP57chr1942791392chr6296415351137DRB1-1371TMMMQGKKKELREQH823
CIC-ZFP57chr1942791392chr6296415351137DRB1-1371VTMMMQGKKKELREQ722
CIC-ZFP57chr1942791392chr6296415351137DRB1-1378TMMMQGKKKELREQH823
CIC-ZFP57chr1942791392chr6296415351137DRB1-1379TMMMQGKKKELREQH823
CIC-ZFP57chr1942791392chr6296415351137DRB1-1380TMMMQGKKKELREQH823
CIC-ZFP57chr1942791392chr6296415351137DRB1-1383TMMMQGKKKELREQH823
CIC-ZFP57chr1942791392chr6296415351137DRB1-1387TMMMQGKKKELREQH823
CIC-ZFP57chr1942791392chr6296415351137DRB1-1391TMMMQGKKKELREQH823
CIC-ZFP57chr1942791392chr6296415351137DRB1-1392TMMMQGKKKELREQH823
CIC-ZFP57chr1942791392chr6296415351137DRB1-1398TMMMQGKKKELREQH823

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Fusion breakpoint peptide structures of CIC-ZFP57

check button3D structures of the fusion breakpoint peptide of 14AA sequence that have potential fusion neoantigens
* The minimum length of the amino acid sequence in RoseTTAFold is 14AA. Here, we predicted the 14AA fusion protein breakpoint sequence not the fusion neoantigen peptide, which is shorter than 14 AA.
File nameBPseqHgeneTgeneHchrHbpTchrTbpAAlen
8334RVTMMMQGKKKELRCICZFP57chr1942791392chr6296415351137

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CIC-ZFP57

check buttonVirtual screening between 25 HLAs (from PDB) and FusionNeoAntigens
* We used Glide to predict the interaction between HLAs and neoantigens.
HLA allelePDB IDFile nameBPseqDocking scoreGlide score
HLA-B14:023BVN8334RVTMMMQGKKKELR-7.15543-7.26883
HLA-B14:023BVN8334RVTMMMQGKKKELR-4.77435-5.80965
HLA-B52:013W398334RVTMMMQGKKKELR-6.80875-6.92215
HLA-B52:013W398334RVTMMMQGKKKELR-4.20386-5.23916
HLA-A11:014UQ28334RVTMMMQGKKKELR-7.5194-8.5547
HLA-A11:014UQ28334RVTMMMQGKKKELR-6.9601-7.0735
HLA-A24:025HGA8334RVTMMMQGKKKELR-7.52403-7.63743
HLA-A24:025HGA8334RVTMMMQGKKKELR-5.82433-6.85963
HLA-B27:056PYJ8334RVTMMMQGKKKELR-3.28285-4.31815
HLA-B44:053DX88334RVTMMMQGKKKELR-5.91172-6.94702
HLA-B44:053DX88334RVTMMMQGKKKELR-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of CIC-ZFP57

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptide sequenceFusionNeoAntigen RNA sequence
CIC-ZFP57chr1942791392chr6296415351019MMQGKKKELTGATGATGCAAGGCAAGAAGAAAGAGC
CIC-ZFP57chr1942791392chr6296415351119MQGKKKELTGATGCAAGGCAAGAAGAAAGAGC
CIC-ZFP57chr1942791392chr629641535919MMMQGKKKELCCATGATGATGCAAGGCAAGAAGAAAGAGC

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
CIC-ZFP57chr1942791392chr629641535722VTMMMQGKKKELREQGAGTGACCATGATGATGCAAGGCAAGAAGAAAGAGCTTCGAGAAC
CIC-ZFP57chr1942791392chr629641535823TMMMQGKKKELREQHTGACCATGATGATGCAAGGCAAGAAGAAAGAGCTTCGAGAACAAC

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Information of the samples that have these potential fusion neoantigens of CIC-ZFP57

check button These samples were reported as having these fusion breakpoints. For individual breakpoints, we checked the open reading frames considering multiple gene isoforms and chose the in-frame fusion genes only. Then, we made fusion protein sequences and predicted the fusion neoantigens. These fusion-positive samples may have these potential fusion neoantigens.
Cancer typeFusion geneHchrHbpHenstTchrTbpTenstSample
BRCACIC-ZFP57chr1942791392ENST00000160740chr629641535ENST00000376881TCGA-BH-A1F0-01A

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Potential target of CAR-T therapy development for CIC-ZFP57

check button Predicted 3D structure. We used RoseTTAFold.

check buttonRetention analysis result of each fusion partner protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, to provide the retention of the transmembrane domain, we only show the protein feature retention information of those transmembrane features


* Minus value of BPloci means that the break point is located before the CDS.
- In-frame and retained 'Transmembrane'.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note

check button Subcellular localization prediction of the transmembrane domain retained fusion proteins
* We used DeepLoc 1.0. The order of the X-axis of the barplot is as follows: Entry_ID, Localization, Type, Nucleus, Cytoplasm, Extracellular, Mitochondrion, Cell_membrane, Endoplasmic_reticulum, Plastid, Golgi.apparatus, Lysosome.Vacuole, Peroxisome. Y-axis is the output score of DeepLoc. Clicking the image will open a new tab with a large image.
HgeneHchrHbpHenstTgeneTchrTbpTenstDeepLoc result

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Related Drugs to CIC-ZFP57

check button Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDrugSourcePMID

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Related Diseases to CIC-ZFP57

check button Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDiseaseSourcePMID

check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource
HgeneCICC4539848MENTAL RETARDATION, AUTOSOMAL DOMINANT 453GENOMICS_ENGLAND;UNIPROT
HgeneCICC0020796Profound Mental Retardation2CTD_human
HgeneCICC0025363Mental Retardation, Psychosocial2CTD_human
HgeneCICC0917816Mental deficiency2CTD_human
HgeneCICC3714756Intellectual Disability2CTD_human
HgeneCICC0027627Neoplasm Metastasis1CTD_human
HgeneCICC0041671Attention Deficit Disorder1CTD_human
HgeneCICC0087012Ataxia, Spinocerebellar1CTD_human
HgeneCICC0752120Spinocerebellar Ataxia Type 11CTD_human
HgeneCICC0752121Spinocerebellar Ataxia Type 21CTD_human
HgeneCICC0752122Spinocerebellar Ataxia Type 41CTD_human
HgeneCICC0752123Spinocerebellar Ataxia Type 51CTD_human
HgeneCICC0752124Spinocerebellar Ataxia Type 6 (disorder)1CTD_human
HgeneCICC0752125Spinocerebellar Ataxia Type 71CTD_human
HgeneCICC1263846Attention deficit hyperactivity disorder1CTD_human
HgeneCICC1321905Minimal Brain Dysfunction1CTD_human
HgeneCICC1510586Autism Spectrum Disorders1CTD_human