◎ Sugi Atlas

Atlas / Gene / TSHZ1

TSHZ1

gene
On this page

Also known as NY-CO-33TSH1

Summary

TSHZ1 (teashirt zinc finger homeobox 1, HGNC:10669) is a protein-coding gene on chromosome 18q22.3, encoding Teashirt homolog 1 (Q6ZSZ6). Probable transcriptional regulator involved in developmental processes.

This gene encodes a colon cancer antigen that was defined by serological analysis of recombinant cDNA expression libraries. The encoded protein is a member of the teashirt C2H2-type zinc-finger protein family and may be involved in transcriptional regulation of developmental processes. Mutations in this gene may be associated with congenital aural atresia syndrome.

Source: NCBI Gene 10194 — RefSeq curated summary.

At a glance

  • Gene–disease (curated): aural atresia, congenital (Strong, GenCC) — +1 more curated relationship
  • GWAS associations: 7
  • Clinical variants (ClinVar): 247 total — 1 likely-pathogenic
  • Phenotypes (HPO): 4
  • MANE Select transcript: NM_001308210

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:10669
Approved symbolTSHZ1
Nameteashirt zinc finger homeobox 1
Location18q22.3
Locus typegene with protein product
StatusApproved
AliasesNY-CO-33, TSH1
Ensembl geneENSG00000179981
Ensembl biotypeprotein_coding
OMIM614427
Entrez10194

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 retained_intron

ENST00000322038, ENST00000560661, ENST00000560918, ENST00000580243, ENST00000584217

RefSeq mRNA: 2 — MANE Select: NM_001308210 NM_001308210, NM_005786

CCDS: CCDS12009, CCDS77199

Canonical transcript exons

ENST00000580243 — 2 exons

ExonStartEnd
ENSE000027055537528544875289944
ENSE000027336707521079775211916

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 94.05.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.4548 / max 320.5638, expressed in 1696 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter IDTPM avgSamples expressed
1707856.09861347
1707844.93711451
1707833.71501151
1707860.4499231
1707820.2541123

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
jejunal mucosaUBERON:000039994.05gold quality
cerebellar vermisUBERON:000472093.47gold quality
ileal mucosaUBERON:000033192.90gold quality
Brodmann (1909) area 23UBERON:001355492.04gold quality
endothelial cellCL:000011591.36gold quality
kidney epitheliumUBERON:000481991.12gold quality
epithelial cell of pancreasCL:000008391.07gold quality
primary visual cortexUBERON:000243690.61gold quality
caput epididymisUBERON:000435890.35gold quality
middle temporal gyrusUBERON:000277190.21gold quality
left ventricle myocardiumUBERON:000656690.18gold quality
placentaUBERON:000198790.02gold quality
cardiac muscle of right atriumUBERON:000337989.97gold quality
stromal cell of endometriumCL:000225589.83gold quality
occipital lobeUBERON:000202189.10gold quality
left ovaryUBERON:000211988.62gold quality
parietal pleuraUBERON:000240088.45gold quality
visceral pleuraUBERON:000240188.40gold quality
ovaryUBERON:000099288.29gold quality
nippleUBERON:000203088.27gold quality
right ovaryUBERON:000211888.19gold quality
superficial temporal arteryUBERON:000161488.16gold quality
corpus epididymisUBERON:000435988.15gold quality
cauda epididymisUBERON:000436088.09gold quality
tibialis anteriorUBERON:000138587.97gold quality
seminal vesicleUBERON:000099887.48gold quality
lower lobe of lungUBERON:000894987.48gold quality
palpebral conjunctivaUBERON:000181287.13gold quality
mammary ductUBERON:000176587.12gold quality
epithelium of mammary glandUBERON:000324487.12gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-ANND-3yes5.13

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

TargetRegulation
HLA-E
MEIS3Repression
TSHZ1

Upstream regulators (CollecTRI, top): MEIS3, TSHZ1

miRNA regulators (miRDB)

154 targeting TSHZ1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-3163100.0077.238605
HSA-MIR-5692A100.0074.406850
HSA-MIR-6748-5P100.0065.811057
HSA-MIR-126-5P100.0072.713180
HSA-MIR-190A-3P100.0080.355520
HSA-LET-7A-3P100.0074.033932
HSA-LET-7B-3P100.0074.083913
HSA-LET-7F-1-3P100.0074.023928
HSA-MIR-98-3P100.0074.083907
HSA-MIR-3924100.0072.092394
HSA-MIR-1277-5P100.0073.955056
HSA-MIR-366299.9973.825684
HSA-MIR-6759-5P99.9966.54785
HSA-MIR-511-3P99.9968.851467
HSA-MIR-1213699.9872.815713
HSA-MIR-56899.9869.862084
HSA-MIR-520D-5P99.9873.344883
HSA-MIR-524-5P99.9873.434882
HSA-MIR-569699.9872.364487
HSA-MIR-4789-5P99.9870.762721
HSA-MIR-4650-5P99.9864.69999
HSA-MIR-480399.9871.993117
HSA-MIR-6793-5P99.9765.95758
HSA-MIR-314899.9775.066478
HSA-MIR-551B-5P99.9671.283493
HSA-MIR-548AT-5P99.9670.832666
HSA-MIR-4666A-3P99.9671.713434
HSA-MIR-548AA99.9670.643753
HSA-MIR-548AP-3P99.9670.643753
HSA-MIR-548T-3P99.9670.643753

Literature-anchored findings (GeneRIF, showing 6)

  • This publication characterizes the mouse ortholog of the human teashirt zinc finger homeobox 1 gene and proposes that the human gene may be a candidate gene for CAA syndrome. (PMID:17586487)
  • a significant up-regulation of BORIS (p<0.001) and TSHZ1 transcripts (p<0.05) for JAs compared to nasal mucosa. (PMID:21874228)
  • Together, these results demonstrate that hemizygosity of TSHZ1 leads to congenital aural atresia as a result of haploinsufficiency (PMID:22152683)
  • TSHZ1 is a key regulator of mammalian olfactory bulb development and function and controls the expression of PROKR2. (PMID:24487590)
  • TSHZ1 levels are reduced in human islets of donors with type 2 diabetes (PMID:25918232)
  • Meta-analysis of genome-wide association studies identifies common susceptibility polymorphisms for colorectal and endometrial cancer near SH2B3 and TSHZ1. (PMID:26621817)

Cross-species orthologs

5 orthologs

OrganismSymbolGene ID
danio_reriotshz1ENSDARG00000005026
mus_musculusTshz1ENSMUSG00000046982
rattus_norvegicusTshz1ENSRNOG00000016246
drosophila_melanogastertshFBGN0003866
drosophila_melanogastertioFBGN0028979

Paralogs (2): TSHZ3 (ENSG00000121297), TSHZ2 (ENSG00000182463)

Protein

Protein identifiers

Teashirt homolog 1 — Q6ZSZ6 (reviewed: Q6ZSZ6)

Alternative names: Antigen NY-CO-33, Serologically defined colon cancer antigen 33

All UniProt accessions (3): Q6ZSZ6, H0YKA1, H0YN23

UniProt curated annotations — full annotation on UniProt →

Function. Probable transcriptional regulator involved in developmental processes. May act as a transcriptional repressor (Potential).

Subunit / interactions. Interacts (via homeobox domain) with APBB1 (via PID domain 1).

Subcellular location. Nucleus.

Tissue specificity. Expressed in brain; strongly reduced in post-mortem elderly subjects with Alzheimer disease.

Disease relevance. Aural atresia, congenital (CAA) [MIM:607842] A rare anomaly of the ear that involves some degree of failure of the development of the external auditory canal. The malformation can also involve the tympanic membrane, ossicles and middle ear space. The inner ear development is most often normal. Different CAA forms are known. CAA type I is characterized by bony or fibrous atresia of the lateral part of the external auditory canal and an almost normal medial part and middle ear. CAA type II is the most frequent type and is characterized by partial or total aplasia of the external auditory canal. CAA type IIA involves an external auditory canal with either complete bony atresia of the medial part or partial aplasia that ends blindly in a fistula leading to a rudimentary tympanic membrane. CAA type IIB is characterized by bony stenosis of the total length of the external auditory canal. CAA type III involves bony atresia of the external auditory canal and a very small or absent middle-ear cavity. The disease is caused by variants affecting the gene represented in this entry.

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

Isoforms (2)

UniProt IDNamesCanonical?
Q6ZSZ6-11yes
Q6ZSZ6-22

RefSeq proteins (2): NP_001295139, NP_005777 (=MANE)

Domains & families (InterPro)

IDNameType
IPR001356HDDomain
IPR013087Znf_C2H2_typeDomain
IPR027008Teashirt_famFamily
IPR058631TSHZ1-3_homeodomainDomain

Pfam: PF26094

UniProt features (29 total): compositionally biased region 9, region of interest 6, zinc finger region 5, sequence conflict 4, chain 1, modified residue 1, splice variant 1, sequence variant 1, DNA-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q6ZSZ6-F154.570.09

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 (1): 765

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 223 (showing top): TAATAAT_MIR126, TTTGTAG_MIR520D, GTGCCTT_MIR506, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_EAR_DEVELOPMENT, CATTTCA_MIR203, AAACCAC_MIR140, GOBP_ANTERIOR_POSTERIOR_PATTERN_SPECIFICATION, GOBP_EMBRYONIC_ORGAN_MORPHOGENESIS, GROSS_HYPOXIA_VIA_ELK3_DN, BILD_E2F3_ONCOGENIC_SIGNATURE, GOBP_MIDDLE_EAR_MORPHOGENESIS, KMCATNNWGGA_UNKNOWN, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, RIGGI_EWING_SARCOMA_PROGENITOR_DN

GO Biological Process (5): regulation of transcription by RNA polymerase II (GO:0006357), anterior/posterior pattern specification (GO:0009952), middle ear morphogenesis (GO:0042474), soft palate development (GO:0060023), regulation of gene expression (GO:0010468)

GO Molecular Function (4): DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA binding (GO:0003677), zinc ion binding (GO:0008270), 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:

CategoryTerms
regulation of DNA-templated transcription1
transcription by RNA polymerase II1
regionalization1
ear morphogenesis1
embryonic morphogenesis1
anatomical structure development1
secondary palate development1
gene expression1
regulation of macromolecule biosynthetic process1
chromatin1
RNA polymerase II transcription regulatory region sequence-specific DNA binding1
DNA-binding transcription factor activity1
regulation of transcription by RNA polymerase II1
nucleic acid binding1
transition metal ion binding1
cation binding1
chromosome1
cellular anatomical structure1
intracellular membrane-bounded organelle1

Protein interactions and networks

STRING

820 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
TSHZ1GGCTO75223736
TSHZ1DOCK11Q5JSL3611
TSHZ1PROKR2Q8NFJ6601
TSHZ1GLYATQ6IB77581
TSHZ1PTGR3Q8N4Q0572
TSHZ1AGAP20933570
TSHZ1SMIM21Q3B7S5473
TSHZ1LGALS4P56470464
TSHZ1SP8Q8IXZ3463
TSHZ1EYA3Q99504451
TSHZ1CBY1Q9Y3M2443
TSHZ1SMARCE1Q969G3438
TSHZ1SP9P0CG40437
TSHZ1GUCY2CP25092435
TSHZ1GGT1P19440433

IntAct

7 interactions, top by confidence:

ABTypeScore
RBBP4TNRC18psi-mi:“MI:0914”(association)0.530
FOXJ2TCERG1psi-mi:“MI:0914”(association)0.350
TSHZ1MEIS2psi-mi:“MI:0914”(association)0.350
SLC1A3DDX11L8psi-mi:“MI:0914”(association)0.350
CTBP1SEC16Apsi-mi:“MI:2364”(proximity)0.270
FHIP1BMED19psi-mi:“MI:2364”(proximity)0.270

BioGRID (21): TSHZ1 (Affinity Capture-MS), TSHZ1 (Affinity Capture-MS), TSHZ1 (Affinity Capture-RNA), TSHZ1 (Affinity Capture-RNA), MEIS2 (Affinity Capture-MS), TSHZ2 (Affinity Capture-MS), PBX3 (Affinity Capture-MS), TSHZ1 (Affinity Capture-MS), TSHZ3 (Affinity Capture-MS), TSHZ1 (Cross-Linking-MS (XL-MS)), TSHZ1 (Cross-Linking-MS (XL-MS)), TSHZ1 (Proximity Label-MS), TSHZ1 (Proximity Label-MS), TSHZ1 (Proximity Label-MS), TSHZ1 (Proximity Label-MS)

ESM2 similar proteins: A0A0R4IYX6, A0A1D5NVS8, A0A1L8H0H2, A0AVK6, A5GFT6, A7XYH5, A7XYJ6, B7ZS37, B8A5Y1, D4A666, E1B7L7, E1BKK0, E1BLP6, F1LMN3, F6YVB9, F8VPJ6, Q12766, Q13029, Q14B70, Q2HNT1, Q2HNT2, Q2KHR2, Q4V9H5, Q58FA4, Q5DTH5, Q5ZIE8, Q5ZIX8, Q5ZJ69, Q5ZM88, Q63679, Q63755, Q68FE9, Q69ZF8, Q6DRC5, Q6P4F7, Q6PCM1, Q6ZSZ6, Q76L83, Q80Y19, Q8BHZ4

Diamond homologs: A5GFT6, B3DJM5, D3ZKB9, P22265, Q2HNT1, Q2HNT2, Q5DTH5, Q63HK5, Q68FE9, Q6ZSZ6, Q8CGV9, Q9NRE2, Q9U3V5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic1
Uncertain significance184
Likely benign40
Benign14

Top pathogenic / likely-pathogenic (1)

Variant IDHGVSClassification
1710246NM_001308210.2(TSHZ1):c.853del (p.Arg285fs)Likely pathogenic

SpliceAI

1311 predictions. Top by Δscore:

VariantEffectΔscore
18:75285443:CCTA:Cacceptor_loss1.0000
18:75285444:CTAGC:Cacceptor_loss1.0000
18:75285445:TA:Tacceptor_loss1.0000
18:75285446:A:AGacceptor_gain1.0000
18:75285446:AGCT:Aacceptor_loss1.0000
18:75285447:G:GCacceptor_gain1.0000
18:75285447:GC:Gacceptor_gain1.0000
18:75285447:GCT:Gacceptor_gain1.0000
18:75285447:GCTT:Gacceptor_gain1.0000
18:75285447:GCTTA:Gacceptor_gain1.0000
18:75211888:G:GTdonor_gain0.9900
18:75261129:GACC:Gdonor_gain0.9900
18:75277233:G:Tdonor_gain0.9900
18:75211914:C:Tdonor_gain0.9800
18:75211914:CAG:Cdonor_loss0.9800
18:75211915:AGG:Adonor_loss0.9800
18:75211916:GGTA:Gdonor_loss0.9800
18:75211917:GTA:Gdonor_loss0.9800
18:75211918:T:Adonor_loss0.9800
18:75261185:A:Tdonor_gain0.9800
18:75284348:T:TAdonor_gain0.9700
18:75284349:A:AAdonor_gain0.9700
18:75285445:TAG:Tacceptor_gain0.9700
18:75285446:A:Tacceptor_gain0.9700
18:75285447:G:Tacceptor_gain0.9700
18:75211885:G:GTdonor_gain0.9600
18:75284317:G:GTdonor_gain0.9600
18:75277193:T:Gdonor_gain0.9500
18:75282741:G:GTdonor_gain0.9500
18:75285444:CTAG:Cacceptor_gain0.9500

AlphaMissense

7117 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
18:75286002:T:AW199R1.000
18:75286002:T:CW199R1.000
18:75286131:G:CG242R1.000
18:75286132:G:AG242D1.000
18:75286143:T:CF246L1.000
18:75286144:T:CF246S1.000
18:75286144:T:GF246C1.000
18:75286145:C:AF246L1.000
18:75286145:C:GF246L1.000
18:75286149:T:AC248S1.000
18:75286149:T:CC248R1.000
18:75286150:G:AC248Y1.000
18:75286150:G:CC248S1.000
18:75286150:G:TC248F1.000
18:75286151:C:GC248W1.000
18:75286158:T:AC251S1.000
18:75286158:T:CC251R1.000
18:75286159:G:AC251Y1.000
18:75286159:G:CC251S1.000
18:75286159:G:TC251F1.000
18:75286160:C:GC251W1.000
18:75286170:T:GY255D1.000
18:75286180:T:AL258Q1.000
18:75286189:T:AL261Q1.000
18:75286189:T:CL261P1.000
18:75286197:C:GH264D1.000
18:75286327:T:AL307Q1.000
18:75286327:T:CL307P1.000
18:75286332:T:AC309S1.000
18:75286332:T:CC309R1.000

dbSNP variants (sampled 300 via entrez): RS1000037204 (18:75269099 A>G), RS1000116347 (18:75236022 C>T), RS1000127108 (18:75219864 G>A,C), RS1000144959 (18:75256270 C>T), RS1000190317 (18:75236196 A>C,G,T), RS1000192809 (18:75221416 A>T), RS1000203295 (18:75271715 C>T), RS1000238248 (18:75265681 A>G), RS1000243417 (18:75261577 G>C), RS1000257819 (18:75234593 T>G), RS1000297431 (18:75254245 T>A), RS1000297457 (18:75225696 G>A,T), RS1000303453 (18:75240402 T>G), RS1000306755 (18:75279067 G>A), RS1000403504 (18:75267411 G>A)

Disease associations

OMIM: gene MIM:614427 | disease phenotypes: MIM:607842

GenCC curated gene-disease

DiseaseClassificationInheritance
aural atresia, congenitalStrongAutosomal dominant
congenital vertical talusLimitedAutosomal dominant

ClinGen Gene-Disease Validity (1)

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

DiseaseClassificationInheritance
aural atresia, congenitalLimitedAD

Mondo (2): aural atresia, congenital (MONDO:0011921), congenital vertical talus (MONDO:0008652)

Orphanet (0):

HPO phenotypes

4 total (4 of 4 shown, HPO-id order):

HPOTerm
HP:0000006Autosomal dominant inheritance
HP:0000405Conductive hearing impairment
HP:0000413Atresia of the external auditory canal
HP:0004409Hyposmia

GWAS associations

7 associations (top):

StudyTraitp-value
GCST001961_3Anorexia nervosa3.000000e-07
GCST002759_27Motion sickness3.000000e-09
GCST003208_4Colorectal or endometrial cancer5.000000e-08
GCST006085_98Prostate cancer4.000000e-08
GCST006628_21Systolic blood pressure1.000000e-12
GCST007267_102Systolic blood pressure1.000000e-11
GCST007576_120Chronotype3.000000e-08

EFO canonical traits (4, from GWAS)

EFO IDTrait name
EFO:0006928motion sickness
EFO:0004230endometrial neoplasm
EFO:0006335systolic blood pressure
EFO:0008328chronotype measurement

MeSH disease descriptors (1)

DescriptorNameTree numbers
C564321Aural Atresia, Congenital (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
Valproic Acidaffects cotreatment, increases expression, affects expression8
Formaldehydedecreases expression2
Phenylmercuric Acetateaffects cotreatment, increases expression2
Cyclosporinedecreases expression2
aristolochic acid Idecreases expression1
FR900359affects phosphorylation1
dicrotophosincreases expression1
testosterone enanthateaffects expression1
methylmercuric chlorideincreases expression1
triphenyl phosphateaffects expression1
propionaldehydedecreases expression1
bisphenol Aaffects cotreatment, increases methylation1
trichostatin Aincreases expression1
beta-lapachonedecreases expression1
sodium arsenitedecreases expression1
cobaltous chlorideincreases expression1
butyraldehydedecreases expression1
hydroquinonedecreases expression1
evodiaminedecreases expression1
CGP 52608affects binding, increases reaction1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamideaffects cotreatment, increases expression1
abrinedecreases expression1
dorsomorphinaffects cotreatment, increases expression1
NSC 689534affects binding, decreases expression1
PCI 5002affects cotreatment, increases expression1
Fulvestrantaffects cotreatment, increases methylation1
Air Pollutantsdecreases expression, increases abundance1
Arsenicaffects methylation1
Atrazineincreases expression1
Benzo(a)pyrenedecreases expression1

Cellosaurus cell lines

4 cell lines: 3 embryonic stem cell, 1 transformed cell line

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

CellosaurusNameCategorySex
CVCL_A7Q6SEES3-1V human TSHZ1, clone1Embryonic stem cellMale
CVCL_A7Q7SEES3-1V human TSHZ1, clone2Embryonic stem cellMale
CVCL_A7Q8SEES3-1V human TSHZ1, clone3Embryonic stem cellMale
CVCL_HC96HEK293 eGFP-TSHZ1Transformed cell lineFemale

Clinical trials (associated diseases)

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

TrialPhaseStatusTitle
NCT00916903Not specifiedTERMINATEDGenetic Disease Gene Identification

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 74

This page pulls from 74 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot