TSC22D2

Chr 3

TSC22 domain family member 2

Also known as: TILZ4a, TILZ4b, TILZ4c

NCBI Gene: 9819 ENSG00000196428 UniProt: O75157 OMIM: 617724

Involved in negative regulation of cell cycle. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

Involved in negative regulation of cell cycle. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.32

Clinical Summary— TSC22D2

⚡

Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.

📋

ClinVar Variants

129 VUS of 141 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.32LOEUF

pLI 0.969

Z-score 3.97

OE 0.13 (0.06–0.32)

Highly constrained

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

Missense Constraint?

0.70Z-score

OE missense 0.91 (0.83–0.98)

395 obs / 436.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.13 (0.06–0.32)

0≤0.351.4

Missense OE?0.91 (0.83–0.98)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

LoF obs/exp: 3 / 23.9Missense obs/exp: 395 / 436.2Syn Z: -1.37

This gene — mechanism propensity

0.2599th %ile

GOF

0.3293th %ile

LOF

0.78top 5%

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

LOFprediction above median · LOEUF 0.32

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

141 submitted variants in ClinVar

ClinVar

Classification Summary

VUS129

Likely Benign4

129

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	129	0	129
Likely Benign	2	2	4
Benign	0	0	0
Total	131	2	133

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

View in ClinVar →

19 pathogenic / likely-pathogenic (of 20) ClinVar copy-number / structural variants overlap TSC22D2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →