MTDH
protein-codingmetadherin
Gene summary
Enables NF-kappaB binding activity; double-stranded RNA binding activity; and transcription coactivator activity. Involved in several processes, including lipopolysaccharide-mediated signaling pathway; positive regulation of angiogenesis; and positive regulation of intracellular signal transduction. Located in endoplasmic reticulum; nuclear body; and perinuclear region of cytoplasm. Implicated in hepatocellular carcinoma. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~86.1 kbGenCC 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 MTDH variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_178812.4. 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.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 3 | ||||
| missense | 92 | 3 | 1 | 96 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 2 | 2 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 100 | 3 | 1 | 104 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_848927.2 | 12 | MANE Select | |
| Ensembl | ENSP00000338235.3 | 12 | MANE Select | |
| RefSeq | NP_001350065.1 | 11 | Standard | |
| RefSeq | NP_001350066.1 | 13 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Gastric Cancer Network 2
- Validated targets of C-MYC transcriptional activation
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
Molecular Function
- RNA polymerase II transcription factor binding
- transcription coactivator activity
- RNA binding
- double-stranded RNA binding
- protein binding
Cellular Component
- fibrillar center
- nucleus
- cytoplasm
- endoplasmic reticulum
- endoplasmic reticulum membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000336273
- Coding exons
- 12
- Length
- 84592
- Individuals with no LoFs
- 125731
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 16
- Defined
- 125747
- p
- 0.0000636
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.01 | 250 | 299 | 0.835 | 0.0000151 | 3734 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00017 | 0.00016 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.000045 | 0.000044 | rare |
| South Asian | 0.00014 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- 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}.;
Recessive Scores
- pRec
- 0.143
Intolerance Scores
- LoFtool
- 0.541
- RVIS EVS
- -0.42
- RVIS percentile EVS
- 25.56
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.539
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |