TMX2

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

Basic information

Region (hg38): 11:57712580-57742987

Previous symbols: [ "TXNDC14" ]

Links

ENSG00000213593 ∙ NCBI:51075 ∙ OMIM:616715 ∙ HGNC:30739 ∙ Uniprot:Q9Y320 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity (Moderate), mode of inheritance: AR
• neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity (Moderate), mode of inheritance: AR
• neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity	AR	General	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	Neurologic	31586943; 31735293

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TMX2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TMX2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				5	1	6
missense		1	17	2		20
nonsense			1			1
start loss						0
frameshift		1	2			3
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1	1		2
non coding				1		1
Total	0	2	20	8	1

Variants in TMX2

This is a list of pathogenic ClinVar variants found in the TMX2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-57712629-T-C		Inborn genetic diseases	Uncertain significance (Mar 11, 2024)
11-57712683-C-T		Inborn genetic diseases	Uncertain significance (Feb 05, 2024)
11-57712695-A-G		Inborn genetic diseases	Likely benign (Jan 21, 2022)
11-57712697-C-T		Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity • Inborn genetic diseases	Uncertain significance (Dec 27, 2023)
11-57712713-T-G			Uncertain significance (-)
11-57712725-T-C		Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity	Uncertain significance (-)
11-57712732-C-T			Benign (Apr 10, 2018)
11-57712746-C-T		Inborn genetic diseases	Uncertain significance (Dec 09, 2023)
11-57712760-G-C		TMX2-related disorder	Likely benign (Jun 01, 2024)
11-57712775-C-T		Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity	Pathogenic (Jan 15, 2020)
11-57712782-A-C		Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity	Pathogenic (Jan 14, 2020)
11-57712784-G-C		Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity	Pathogenic (Jan 14, 2020)
11-57712798-C-G			Uncertain significance (-)
11-57712800-TTGAC-T		Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity	Likely pathogenic (-)
11-57737605-C-A			Uncertain significance (Nov 17, 2022)
11-57737616-G-A			Likely benign (Dec 01, 2022)
11-57737636-G-A		Inborn genetic diseases	Uncertain significance (Mar 12, 2024)
11-57737988-A-G		-	no classification for the single variant (-)
11-57737994-G-C		Inborn genetic diseases	Uncertain significance (Mar 12, 2024)
11-57737996-A-G		Inborn genetic diseases	Uncertain significance (Mar 01, 2023)
11-57738364-G-A			Uncertain significance (Dec 08, 2022)
11-57738373-A-AC		Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity	Pathogenic (Jan 14, 2020)
11-57738380-CT-C		See cases	Conflicting classifications of pathogenicity (Nov 17, 2022)
11-57738665-A-T		Inborn genetic diseases	Uncertain significance (Aug 12, 2021)
11-57738676-C-T		See cases • Inborn genetic diseases	Conflicting classifications of pathogenicity (Aug 11, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TMX2	protein_coding	protein_coding	ENST00000278422	8	28374

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.647	0.352	125731	0	17	125748	0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.219	164	172	0.953	0.00000944	1920
Missense in Polyphen		52	57.227	0.90866		640
Synonymous	-1.87	83	63.9	1.30	0.00000294	585
Loss of Function	3.07	3	16.4	0.183	7.92e-7	187

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000181	0.000181
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000704	0.0000703
Middle Eastern	0.00	0.00
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Intolerance Scores

• loftool: 0.274
• rvis_EVS: -0.27
• rvis_percentile_EVS: 34.6

Haploinsufficiency Scores

• pHI: 0.137
• hipred: N
• hipred_score: 0.344
• ghis: 0.587

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0159

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Tmx2

Gene ontology

• Biological process: biological_process;cell redox homeostasis
• Cellular component: cellular_component;cell;integral component of membrane
• Molecular function: molecular_function