TSHZ3

protein-coding

teashirt zinc finger homeobox 3, the group of Zinc fingers C2H2-type|ZF class homeoboxes and pseudogenes

Gene summary

This gene encodes a zinc-finger transcription factor that regulates smooth muscle cell differentiation in the developing urinary tract. Consistent with this role, mice in which this gene has been inactivated exhibit abnormal gene expression in urinary tract smooth muscle cell precursors and kidney defects including hydronephrosis. The encoded transcription factor comprises a gene silencing complex that inhibits caspase expression. Reduced expression of this gene and consequent caspase upregulation may be correlated with progression of Alzheimer's disease in human patients. [provided by RefSeq, Jul 2016]

Previous symbols:

ZNF537

MANE transcript

NM_020856.4

Inheritance

ClinVar variants

P:1U:164B:33

Top phenotype

TSHZ3-related disorder

gnomAD constraint

pLI —, LoF o/e 0.11

Max pathogenic AF

—

Genomic locus

chr19:31,149,979-31,349,436

External References & Databases

Ensembl (ENSG00000121297)

Transcript & Mutation Effects

hg38 • Region Span ~199.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

congenital anomaly of kidney and urinary tractLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0019719

Submitter: Ambry Genetics

autism spectrum disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0005258

Submitter: Ambry Genetics

congenital anomaly of kidney and urinary tractMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0019719

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TSHZ3 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 156

TSHZ3-related disorderTotal: 38

not providedTotal: 9

Congenital anomaly of kidney and urinary tractTotal: 5

Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020856.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				23 clinvar	1 clinvar	24
missense		1 clinvar	162 clinvar	8 clinvar	1 clinvar	172
nonsense			1 clinvar			1
start loss			1 clinvar			1
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	1	164	31	2	198

Highest pathogenic variant AF is 0.00004778157

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020856.4	RefSeq	NP_065907.2	2	MANE Select
ENST00000240587.5	Ensembl	ENSP00000240587.4	2	MANE Select
ENST00000558569.1	Ensembl	ENSP00000475613.1	2	Standard
ENST00000558569.2	Ensembl	ENSP00000475613.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of transcription by RNA polymerase II
regulation of respiratory gaseous exchange by neurological system process
regulation of transcription by RNA polymerase II
multicellular organism development
negative regulation of transcription, DNA-templated

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
DNA binding
chromatin binding
protein binding
metal ion binding

Cellular Component

nucleus
nucleoplasm
growth cone

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000240587
Coding exons: 2
Length: 74603
Individuals with no LoFs: 125744
Homozygous LoFs: 0
Heterozygous LoFs: 4
Defined: 125748
p: 0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.83	519	651	0.798	0.0000408	7131
Missense (PolyPhen)		165	266.96	0.61806		3070
Synonymous	-0.968	320	299	1.07	0.0000224	2142
Loss of Function	4.30	3	27.2	0.110	0.00000132	371

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcriptional regulator involved in developmental processes. Function in association with APBB1, SET and HDAC factors as a transcriptional repressor, that inhibits the expression of CASP4. TSHZ3-mediated transcription repression involves the recruitment of histone deacetylases HDAC1 and HDAC2. Associates with chromatin in a region surrounding the CASP4 transcriptional start site(s) (PubMed:19343227). Regulates the development of neurons involved in both respiratory rhythm and airflow control. Promotes maintenance of nucleus ambiguus (nA) motoneurons, which govern upper airway function, and establishes a respiratory rhythm generator (RRG) activity compatible with survival at birth. Involved in the differentiation of the proximal uretic smooth muscle cells during developmental processes. Involved in the up-regulation of myocardin, that directs the expression of smooth muscle cells in the proximal ureter (By similarity). Involved in the modulation of glutamatergic synaptic transmission and long-term synaptic potentiation (By similarity). {ECO:0000250|UniProtKB:Q8CGV9, ECO:0000269|PubMed:19343227}.;
Disease: DISEASE: Note=TSHZ3 haploinsufficiency due to proximal chromosome 19q13.11 deletions causes a neurodevelopmental disorder characterized by developmental delay, absent or delayed speech, intellectual disability, and autistic features. Some patients may have reanal tract abnormalities. {ECO:0000269|PubMed:27668656}.;

Recessive Scores

pRec: 0.122

Intolerance Scores

LoFtool: 0.135
RVIS EVS: -1.72
RVIS percentile EVS: 2.49

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.762

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium