TSHZ3

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

Basic information

Region (hg38): 19:31149979-31349436

Previous symbols: [ "ZNF537" ]

Links

ENSG00000121297 ∙ NCBI:57616 ∙ OMIM:614119 ∙ HGNC:30700 ∙ Uniprot:Q63HK5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital anomaly of kidney and urinary tract (Limited), mode of inheritance: AD
• autism spectrum disorder (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TSHZ3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TSHZ3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				19	4	23
missense			58	5	1	64
nonsense						0
start loss			1			1
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding						0
Total	0	0	59	24	5

Variants in TSHZ3

This is a list of pathogenic ClinVar variants found in the TSHZ3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-31276559-T-A		not specified	Uncertain significance (Jan 23, 2024)
19-31276590-G-A		not specified	Uncertain significance (Oct 10, 2023)
19-31276601-G-A		TSHZ3-related disorder	Likely benign (Nov 07, 2019)
19-31276648-T-A		not specified	Uncertain significance (Feb 02, 2024)
19-31276649-C-T		TSHZ3-related disorder	Likely benign (Jun 24, 2019)
19-31276759-C-T		not specified	Uncertain significance (Jun 22, 2021)
19-31276773-G-C		not specified	Uncertain significance (Sep 06, 2022)
19-31276782-C-T		not specified	Uncertain significance (May 27, 2022)
19-31276852-A-C		not specified	Uncertain significance (May 09, 2023)
19-31276870-C-T		not specified	Uncertain significance (Sep 01, 2021)
19-31276958-G-A			Likely benign (Dec 01, 2022)
19-31276966-T-G		not specified	Uncertain significance (Oct 26, 2021)
19-31276975-C-T		not specified	Uncertain significance (Feb 06, 2023)
19-31277139-G-A		not specified	Uncertain significance (Jan 30, 2024)
19-31277148-G-A		not specified	Uncertain significance (Jun 10, 2024)
19-31277152-C-T		TSHZ3-related disorder	Uncertain significance (Mar 26, 2024)
19-31277167-C-T		not specified	Uncertain significance (Mar 23, 2022)
19-31277191-T-C		not specified	Uncertain significance (Sep 16, 2021)
19-31277216-C-T		TSHZ3-related disorder	Likely benign (Feb 01, 2023)
19-31277280-G-A		not specified	Uncertain significance (Jun 10, 2022)
19-31277291-C-T		not specified	Uncertain significance (Sep 22, 2023)
19-31277302-C-A		not specified	Uncertain significance (Oct 04, 2022)
19-31277305-C-T		not specified	Uncertain significance (Jan 07, 2022)
19-31277331-G-A		not specified	Uncertain significance (Apr 25, 2022)
19-31277332-T-C		not specified	Uncertain significance (Jan 22, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TSHZ3	protein_coding	protein_coding	ENST00000240587	2	74603

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.991	0.00947	125744	0	4	125748	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.83	519	651	0.798	0.0000408	7131
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000619	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000177	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

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

Haploinsufficiency Scores

• pHI: 0.866
• hipred: Y
• hipred_score: 0.728
• ghis: 0.574

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.762

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tshz3
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; renal/urinary system phenotype

Gene ontology

• 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;positive regulation of synaptic transmission, glutamatergic;long-term synaptic potentiation
• Cellular component: nucleus;nucleoplasm;growth cone
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;chromatin binding;protein binding;metal ion binding