TSHZ2

Chr 20

teashirt zinc finger homeobox 2

Also known as: C20orf17, OVC10-2, TSH2, ZABC2, ZNF218

TSHZ2 encodes a transcriptional repressor containing zinc fingers and a homeobox DNA-binding domain that regulates developmental processes. Mutations cause autosomal dominant developmental delays, intellectual disability, and congenital anomalies including heart defects and genitourinary malformations. This gene is highly constrained against loss-of-function variants, indicating that even single functional copies are critical for normal development.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
5
Pubs (1 yr)
10
P/LP submissions
0%
P/LP missense
0.31
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryTSHZ2
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
10 unique Pathogenic / Likely Pathogenic· 161 VUS of 187 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.31LOEUF
pLI 0.981
Z-score 4.63
OE 0.15 (0.070.31)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
0.60Z-score
OE missense 0.93 (0.871.00)
556 obs / 597.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.15 (0.070.31)
00.351.4
Missense OE0.93 (0.871.00)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 5 / 34.2Missense obs/exp: 556 / 597.4Syn Z: -0.12
DN
0.3594th %ile
GOF
0.2099th %ile
LOF
0.83top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.31

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

187 submitted variants in ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic2
VUS161
Likely Benign6
8
Pathogenic
2
Likely Pathogenic
161
VUS
6
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
0
0
2
0
2
VUS
0
157
4
0
161
Likely Benign
0
5
0
1
6
Benign
0
0
0
0
0
Total0162141177

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TSHZ2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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