TMX2

Chr 11AR

thioredoxin related transmembrane protein 2

Also known as: CGI-31, NEDMCMS, PDIA12, PIG26, TXNDC14

The protein is a disulfide isomerase that catalyzes protein folding and thiol-disulfide reactions in the endoplasmic reticulum and regulates cellular redox state, protein folding, and mitochondrial activity. Biallelic mutations cause neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity with autosomal recessive inheritance. The gene is highly constrained against loss-of-function variants (LOEUF 0.47), indicating intolerance to protein-disrupting changes.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.471 OMIM phenotype
Clinical SummaryTMX2
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.65) — some intolerance to loss-of-function variants.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.47LOEUF
pLI 0.647
Z-score 3.07
OE 0.18 (0.080.47)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.22Z-score
OE missense 0.95 (0.841.08)
164 obs / 172.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.18 (0.080.47)
00.351.4
Missense OE0.95 (0.841.08)
00.61.4
Synonymous OE1.30
01.21.6
LoF obs/exp: 3 / 16.4Missense obs/exp: 164 / 172.1Syn Z: -1.87

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TMX2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

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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