PYROXD1

pyridine nucleotide-disulphide oxidoreductase domain 1

Basic information

Region (hg38): 12:21437615-21471250

Links

ENSG00000121350 ∙ NCBI:79912 ∙ OMIM:617220 ∙ HGNC:26162 ∙ Uniprot:Q8WU10 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• myofibrillar myopathy 8 (Strong), mode of inheritance: AR
• myofibrillar myopathy 8 (Moderate), mode of inheritance: AR
• myofibrillar myopathy 8 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myopathy, myofibrillar 8	AR	Cardiovascular	Though not common, some individuals can have cardiovascular manifestations, and awareness can allow medical management	Cardiovascular; Musculoskeletal	27745833; 30345904; 30515627; 32037607; 33694278

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PYROXD1 gene.

• not provided (9 variants)
• Myofibrillar myopathy 8 (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PYROXD1 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			1	50	3	54
missense	2	1	117	6		126
nonsense	1		1			2
start loss						0
frameshift	5	2	1			8
inframe indel		1	4			5
splice donor/acceptor (+/-2bp)	1	4				5
splice region			9	6	4	19
non coding			151	113	84	348
Total	9	8	275	169	87

Highest pathogenic variant AF is 0.0000263

Variants in PYROXD1

This is a list of pathogenic ClinVar variants found in the PYROXD1 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-21437623-A-C			Benign (Jul 09, 2018)
12-21437666-C-T			Likely benign (Jul 10, 2018)
12-21437676-CCA-C			Likely benign (Jul 09, 2018)
12-21437687-T-C		Myofibrillar myopathy 8	Benign (Nov 07, 2021)
12-21437742-G-A			Likely benign (Jul 13, 2023)
12-21437748-TC-T			Pathogenic (Nov 24, 2021)
12-21437749-C-A		Inborn genetic diseases	Uncertain significance (Aug 17, 2022)
12-21437749-C-T		Inborn genetic diseases	Uncertain significance (Nov 17, 2022)
12-21437752-C-G		Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 03, 2024)
12-21437770-G-T			Uncertain significance (Nov 09, 2021)
12-21437782-G-A			Uncertain significance (Jul 15, 2022)
12-21437796-C-T			Likely benign (Mar 12, 2022)
12-21437798-T-A			Uncertain significance (Mar 02, 2022)
12-21437812-C-A			Likely benign (Jan 08, 2024)
12-21437820-G-A			Uncertain significance (Aug 04, 2022)
12-21437825-G-T			Likely benign (Dec 03, 2023)
12-21437833-G-A			Likely benign (Aug 26, 2022)
12-21437833-G-T			Likely benign (Dec 23, 2021)
12-21437854-C-A		Myofibrillar myopathy 8	Benign (Nov 07, 2021)
12-21438095-G-C			Likely benign (Jul 10, 2018)
12-21440073-G-C			Likely benign (Jul 09, 2018)
12-21440103-T-C			Benign (Jul 09, 2018)
12-21440347-TTC-T			Likely benign (Dec 15, 2023)
12-21440348-T-C			Likely benign (Sep 12, 2022)
12-21440349-C-G			Likely benign (Jun 25, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PYROXD1	protein_coding	protein_coding	ENST00000240651	12	32752

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.30e-9	0.870	125670	0	78	125748	0.000310

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0969	252	256	0.983	0.0000123	3285
Missense in Polyphen		60	78.034	0.7689		989
Synonymous	0.0292	91	91.4	0.996	0.00000476	907
Loss of Function	1.69	17	26.4	0.644	0.00000140	345

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000949	0.000946
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000217
Finnish	0.0000468	0.0000462
European (Non-Finnish)	0.000369	0.000352
Middle Eastern	0.000218	0.000217
South Asian	0.000284	0.000261
Other	0.000503	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in cellular response to oxidative stress. {ECO:0000269|PubMed:27745833}.
• Disease: DISEASE: Myopathy, myofibrillar, 8 (MFM8) [MIM:617258]: A form of myofibrillar myopathy, a group of chronic neuromuscular disorders characterized at ultrastructural level by disintegration of the sarcomeric Z disk and myofibrils, and replacement of the normal myofibrillar markings by small dense granules, or larger hyaline masses, or amorphous material. MFM8 is an autosomal recessive form, clinically characterized by slowly progressive symmetrical weakness affecting both proximal and distal muscles, with normal to moderately elevated creatine kinase. Mild facial weakness, a high palate, nasal speech, and swallowing difficulties are typical features, mild restrictive lung disease is common, and late-onset cardiac involvement may be present. {ECO:0000269|PubMed:27745833}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.0932

Intolerance Scores

• loftool: 0.499
• rvis_EVS: -0.53
• rvis_percentile_EVS: 20.7

Haploinsufficiency Scores

• pHI: 0.0832
• hipred: N
• hipred_score: 0.251
• ghis: 0.588

Essentials

• essential_gene_CRISPR: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.712

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pyroxd1
• Phenotype: growth/size/body region phenotype; skeleton phenotype; digestive/alimentary phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); embryo phenotype

Zebrafish Information Network

• Gene name: pyroxd1
• Affected structure: skeletal muscle
• Phenotype tag: abnormal
• Phenotype quality: broken

Gene ontology

• Biological process: cellular response to oxidative stress;oxidation-reduction process
• Cellular component: nucleus;sarcomere
• Molecular function: protein binding;oxidoreductase activity