TMX1

protein-coding

thioredoxin related transmembrane protein 1, 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, and one transmembrane domain. Unlike most members of this gene family, it lacks a C-terminal ER-retention sequence. The mature membrane-bound protein can both oxidize and reduce disulfide bonds and acts selectively on membrane-associated polypeptides. [provided by RefSeq, Jan 2017]

Previous symbols:

TXNDC
TXNDC1

MANE transcript

NM_030755.5

Inheritance

—

ClinVar variants

U:41B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.45

Max pathogenic AF

—

Genomic locus

chr14:51,240,162-51,257,655

External References & Databases

Ensembl (ENSG00000139921)

Transcript & Mutation Effects

hg38 • Region Span ~17.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TMX1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 35

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_030755.5. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	1 clinvar		2
missense			36 clinvar	1 clinvar		37
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	41	2	0	43

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_030755.5	RefSeq	NP_110382.3	8	MANE Select
ENST00000457354.7	Ensembl	ENSP00000393316.2	8	MANE Select
ENST00000556683.1	Ensembl	ENSP00000451585.1	3	Standard
ENST00000898229.1	Ensembl	ENSP00000568288.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

response to endoplasmic reticulum stress
cell redox homeostasis
oxidation-reduction process

Molecular Function

disulfide oxidoreductase activity

Cellular Component

endoplasmic reticulum membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000457354
Coding exons: 8
Length: 15880
Individuals with no LoFs: 124779
Homozygous LoFs: 0
Heterozygous LoFs: 16
Defined: 124795
p: 0.0000641

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.230	159	151	1.05	0.00000760	1806
Missense (PolyPhen)		28	37.547	0.74574		434
Synonymous	-1.64	70	54.6	1.28	0.00000281	517
Loss of Function	2.12	8	17.6	0.454	8.45e-7	202

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00013	rare
Latino/Admixed American	0.000031	0.000029	rare
Ashkenazi Jewish	0.00040	0.00040	rare
East Asian	0.000056	0.000056	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000062	0.000053	rare
South Asian	0.000069	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May participate in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyze dithiol-disulfide exchange reactions.;

Recessive Scores

pRec: 0.113

Intolerance Scores

LoFtool: 0.535
RVIS EVS: -0.58
RVIS percentile EVS: 18.44

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.714

Gene Damage Prediction

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