MTDH

metadherin

Basic information

Region (hg38): 8:97644183-97730260

Links

ENSG00000147649 ∙ NCBI:92140 ∙ OMIM:610323 ∙ HGNC:29608 ∙ Uniprot:Q86UE4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

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

• Inborn genetic diseases (31 variants)
• not provided (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MTDH 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						0
missense			30	1	2	33
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	31	1	2

Variants in MTDH

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

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

Position	Type	Phenotype	Significance	ClinVar
8-97644516-C-T		not specified	Uncertain significance (Aug 09, 2021)
8-97644573-G-A		not specified	Uncertain significance (Apr 07, 2022)
8-97644588-G-A		not specified	Uncertain significance (Jul 19, 2022)
8-97644621-G-A		not specified	Uncertain significance (Mar 06, 2023)
8-97644666-G-A			Benign (Dec 31, 2019)
8-97644714-G-C		not specified	Uncertain significance (Nov 07, 2023)
8-97644721-C-T		not specified	Uncertain significance (Mar 29, 2023)
8-97644787-C-G		not specified	Uncertain significance (Nov 16, 2021)
8-97644790-T-G		not specified	Uncertain significance (Aug 10, 2021)
8-97644792-C-A		not specified	Uncertain significance (Oct 25, 2023)
8-97644793-C-T		not specified	Uncertain significance (Nov 03, 2022)
8-97644802-C-T		not specified	Uncertain significance (Oct 27, 2021)
8-97644813-C-G			Benign (Mar 01, 2023)
8-97661096-G-A		not specified	Uncertain significance (May 11, 2022)
8-97661097-C-T		not specified	Uncertain significance (May 11, 2022)
8-97661153-A-G		not specified	Uncertain significance (Jun 06, 2023)
8-97661157-A-T		not specified	Uncertain significance (Apr 25, 2022)
8-97661162-A-G		not specified	Uncertain significance (Jun 12, 2023)
8-97686747-A-T		not specified	Uncertain significance (May 09, 2023)
8-97687479-C-T		not specified	Uncertain significance (Jan 30, 2024)
8-97687518-A-G		not specified	Uncertain significance (Jan 26, 2022)
8-97687557-G-A		not specified	Uncertain significance (Apr 22, 2022)
8-97687570-C-T		not specified	Uncertain significance (Jun 13, 2022)
8-97689052-A-G		not specified	Uncertain significance (Dec 06, 2023)
8-97689058-C-G		not specified	Uncertain significance (Oct 27, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MTDH	protein_coding	protein_coding	ENST00000336273	12	84592

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.329	0.671	125731	0	16	125747	0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.01	250	299	0.835	0.0000151	3734
Missense in Polyphen		89	120.22	0.74033		1531
Synonymous	0.884	103	115	0.895	0.00000591	1136
Loss of Function	3.94	7	30.5	0.229	0.00000146	371

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000621	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.000167	0.000163
Finnish	0.000139	0.000139
European (Non-Finnish)	0.0000445	0.0000439
Middle Eastern	0.000167	0.000163
South Asian	0.000141	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Downregulates SLC1A2/EAAT2 promoter activity when expressed ectopically. Activates the nuclear factor kappa-B (NF- kappa-B) transcription factor. Promotes anchorage-independent growth of immortalized melanocytes and astrocytes which is a key component in tumor cell expansion. Promotes lung metastasis and also has an effect on bone and brain metastasis, possibly by enhancing the seeding of tumor cells to the target organ endothelium. Induces chemoresistance. {ECO:0000269|PubMed:15927426, ECO:0000269|PubMed:16452207, ECO:0000269|PubMed:18316612, ECO:0000269|PubMed:19111877}.
• Pathway: Gastric Cancer Network 2;Validated targets of C-MYC transcriptional activation (Consensus)

Recessive Scores

• pRec: 0.143

Intolerance Scores

• loftool: 0.541
• rvis_EVS: -0.42
• rvis_percentile_EVS: 25.56

Haploinsufficiency Scores

• pHI: 0.422
• hipred: Y
• hipred_score: 0.546
• ghis: 0.604

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.539

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mtdh
• Phenotype: immune system phenotype; liver/biliary system phenotype; neoplasm; 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); normal phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); reproductive system phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;positive regulation of autophagy;lipopolysaccharide-mediated signaling pathway;negative regulation of apoptotic process;positive regulation of I-kappaB kinase/NF-kappaB signaling;positive regulation of angiogenesis;positive regulation of NF-kappaB transcription factor activity;positive regulation of protein kinase B signaling;bicellular tight junction assembly;positive regulation of nucleic acid-templated transcription
• Cellular component: fibrillar center;nucleus;cytoplasm;endoplasmic reticulum;endoplasmic reticulum membrane;bicellular tight junction;integral component of membrane;apical plasma membrane;nuclear body;nuclear membrane;intercellular canaliculus;perinuclear region of cytoplasm
• Molecular function: RNA polymerase II transcription factor binding;transcription coactivator activity;RNA binding;double-stranded RNA binding;protein binding;NF-kappaB binding