TSC22D1

Chr 13

TSC22 domain family member 1

Also known as: HUCEP-2, Ptg-2, TGFB1I4, TSC22

NCBI Gene: 8848 ENSG00000102804 UniProt: Q15714

This gene encodes a leucine zipper transcription factor that represses transcription of multiple genes including C-type natriuretic peptide and regulates TGF-beta signaling pathways involved in apoptosis and tumor suppression. The gene is highly constrained against loss-of-function variants (pLI 0.96, LOEUF 0.33), but no established Mendelian disease associations have been reported in the provided data. A promoter polymorphism has been associated with diabetic nephropathy susceptibility.

ResearchSummary from RefSeq, UniProt

This gene encodes a member of the TSC22 domain family of leucine zipper transcription factors. The encoded protein is stimulated by transforming growth factor beta, and regulates the transcription of multiple genes including C-type natriuretic peptide. The encoded protein may play a critical role in tumor suppression through the induction of cancer cell apoptosis, and a single nucleotide polymorphism in the promoter of this gene has been associated with diabetic nephropathy. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2011]

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

0.33

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.33LOEUF

pLI 0.960

Z-score 4.43

OE 0.16 (0.08–0.33)

Highly constrained

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

Missense Constraint?

-0.88Z-score

OE missense 1.10 (1.03–1.18)

621 obs / 562.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.16 (0.08–0.33)

0≤0.351.4

Missense OE?1.10 (1.03–1.18)

0≤0.61.4

Synonymous OE?1.28

0≤1.21.6

LoF obs/exp: 5 / 32.1Missense obs/exp: 621 / 562.2Syn Z: -3.28

Background carrier burden — how many people carry a rare variant somewhere in TSC22D1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 51

1,574 rare PASS variants

Rare truncating (LoF)

1 in 760

66 rare PASS variants

Rare synonymous (reference)

1 in 76

652 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TSC22D1. 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 58	1 in 2,700
South Asian	~43k	1 in 43	1 in 4,200
Remaining (unassigned)	~30k	1 in 41	1 in 520
European (Finnish)	~27k	1 in 210	1 in 1,200
Admixed American	~22k	1 in 37	1 in 710
African / African American	~21k	1 in 36	1 in 1,200
East Asian	~20k	1 in 48	1 in 1,700
Ashkenazi Jewish	~13k	1 in 120	none seen
Middle Eastern	~2,884	1 in 45	≈ 1 in 720

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 ↓