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…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.32

LOEUF· LoF intol.

LOF

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in TSC22D2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 59

1,094 rare PASS variants

Rare truncating (LoF)

1 in 4,700

24 rare PASS variants

Rare synonymous (reference)

1 in 100

548 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TSC22D2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 66	1 in 4,200
South Asian	~43k	1 in 51	1 in 3,500
Remaining (unassigned)	~30k	1 in 57	1 in 5,000
European (Finnish)	~27k	1 in 190	1 in 3,700
Admixed American	~22k	1 in 48	none seen
African / African American	~21k	1 in 49	≈ 1 in 5,500
East Asian	~20k	1 in 54	none seen
Ashkenazi Jewish	~13k	1 in 140	none seen
Middle Eastern	~2,884	1 in 45	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓