GeneBe

TMX2

protein-coding

thioredoxin related transmembrane protein 2, the group of Protein disulfide isomerases|Thioredoxin domain containing

Gene summary

This gene encodes a member of the disulfide isomerase (PDI) family of endoplasmic reticulum (ER) proteins that catalyze protein folding and thiol-disulfide interchange reactions. The encoded protein has an N-terminal ER-signal sequence, a catalytically active thioredoxin domain, one transmembrane domain and a C-terminal ER-retention sequence. This protein is enriched on the mitochondria-associated-membrane of the ER via palmitoylation of two of its cytosolically exposed cysteines. [provided by RefSeq, Jan 2017]

Previous symbols:
  • TXNDC14

MANE transcript

NM_015959.4

Inheritance

AR

ClinVar variants

P:11U:55B:13

Top phenotype

Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity

gnomAD constraint

pLI —, LoF o/e 0.18

Max pathogenic AF

—

Genomic locus

chr11:57,712,580-57,742,987

External References & Databases

Ensembl (ENSG00000213593)NCBI Gene (51075)OMIM (616715)HGNC:30739GenCCUniProt (Q9Y320)AlphaFoldClinVar (TMX2)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~30.4 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorder with microcephaly, cortical malformations, and spasticitySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032887

Submitter: G2P

neurodevelopmental disorderSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

neurodevelopmental disorder with microcephaly, cortical malformations, and spasticityMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0032887

Submitter: Ambry Genetics

neurodevelopmental disorder with microcephaly, cortical malformations, and spasticitySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032887

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticityAR

Manifestation: Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 31586943; 31735293Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TMX2 variants in ClinVar

7 Conditions Cataloged
Inborn genetic diseasesTotal: 45
not providedTotal: 20
Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticityTotal: 14
not specifiedTotal: 9
TMX2-related disorderTotal: 7
See casesTotal: 2
Abnormality of the nervous systemTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015959.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
9
clinvar
1
clinvar
 10
missense
4
clinvar
2
clinvar
50
clinvar
3
clinvar
 59
nonsense
1
clinvar
2
clinvar
 3
start loss
0
frameshift
1
clinvar
2
clinvar
3
clinvar
 6
splice donor/acceptor (+/-2bp)
1
clinvar
 1
Total745512179

Highest pathogenic variant AF is 0.00003035958

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 89 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_015959.4RefSeqNP_057043.18MANE Select
ENST00000278422.9EnsemblENSP00000278422.48MANE Select
NM_001144012.3RefSeqNP_001137484.17Standard
NM_001347890.2RefSeqNP_001334819.18Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

  • biological_process
  • cell redox homeostasis

Molecular Function

  • molecular_function

Cellular Component

  • cellular_component
  • cell
  • integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000278422
Coding exons
8
Length
28374
Individuals with no LoFs
125731
Homozygous LoFs
0
Heterozygous LoFs
17
Defined
125748
p
0.0000676
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.2191641720.9530.000009441920
Missense (PolyPhen)5257.2270.90866640
Synonymous-1.878363.91.300.00000294585
Loss of Function3.07316.40.1837.92e-7187

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000120.00012rare
Latino/Admixed American0.0000580.000058rare
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish0.0000460.000046rare
European (Non-Finnish)0.0000700.000070rare
South Asian0.000130.00013rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

LoFtool
0.274
RVIS EVS
-0.27
RVIS percentile EVS
34.6

Essentials

Essential (CRISPR)
E
Essential (CRISPR2)
S
Essential (gene trap)
E
Indispensability pred.
N
Indispensability score
0.0159

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
Feedback | API | MCP | Annotate VCF | Sitemap | About | Privacy & Terms
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.