THEMIS

Chr 6

thymocyte selection associated

Also known as: C6orf190, C6orf207, GASP, SPOT, THEMIS1, TSEPA

NCBI Gene: 387357ENSG00000172673UniProt: Q8N1K5

This gene encodes a protein that plays a regulatory role in both positive and negative T-cell selection during late thymocyte development. The protein functions through T-cell antigen receptor signaling, and is necessary for proper lineage commitment and maturation of T-cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

0
Active trials
16
Pathogenic / LP
123
ClinVar variants
11
Pubs (1 yr)
-0.6
Missense Z
0.87
LOEUF
Clinical Summary— THEMIS
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
16 Pathogenic / Likely Pathogenic· 99 VUS of 123 total submissions
Some data sources returned errors (1)

pubtator: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.87LOEUF
pLI 0.000
Z-score 2.05
OE 0.55 (0.35–0.87)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.58Z-score
OE missense 1.09 (1.00–1.18)
381 obs / 350.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.55 (0.35–0.87)
0≤0.351.4
Missense OE1.09 (1.00–1.18)
0≤0.61.4
Synonymous OE1.17
0≤1.21.6
LoF obs/exp: 13 / 23.8Missense obs/exp: 381 / 350.3Syn Z: -1.49
DN
DN
0.6453th %ile
GOF
0.6346th %ile
LOF
0.3165th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

123 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic3
VUS99
Likely Benign7
Benign1
13
Pathogenic
3
Likely Pathogenic
99
VUS
7
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
13
0
13
Likely Pathogenic
0
0
3
0
3
VUS
0
90
9
0
99
Likely Benign
0
4
3
0
7
Benign
0
1
0
0
1
Total095280123

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

View in ClinVar →

THEMIS · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients