SMAD5
SMAD family member 5, the group of SMAD family
Basic information
Region (hg38): 5:136132845-136188747
Previous symbols: [ "MADH5" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the SMAD5 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 | 10 | 10 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 10 | 0 | 0 |
Variants in SMAD5
This is a list of pathogenic ClinVar variants found in the SMAD5 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 5-136153810-G-A | not specified | Uncertain significance (Nov 12, 2021) | ||
| 5-136160885-A-G | not specified | Uncertain significance (Sep 21, 2021) | ||
| 5-136161014-T-C | not specified | Uncertain significance (Apr 06, 2024) | ||
| 5-136161041-C-T | not specified | Uncertain significance (Mar 01, 2024) | ||
| 5-136163293-A-G | not specified | Uncertain significance (Dec 01, 2023) | ||
| 5-136163295-A-G | not specified | Uncertain significance (Mar 18, 2024) | ||
| 5-136163310-C-G | not specified | Uncertain significance (Apr 26, 2023) | ||
| 5-136163317-G-T | not specified | Uncertain significance (Oct 14, 2023) | ||
| 5-136163368-T-C | not specified | Uncertain significance (Oct 26, 2022) | ||
| 5-136172478-A-G | not specified | Uncertain significance (Oct 29, 2021) | ||
| 5-136172626-T-C | not specified | Uncertain significance (Dec 15, 2023) | ||
| 5-136174568-A-G | not specified | Uncertain significance (Jul 06, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| SMAD5 | protein_coding | protein_coding | ENST00000545279 | 7 | 55902 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.998 | 0.00162 | 395 | 124736 | 0 | 125131 | 0.944 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.00 | 117 | 251 | 0.467 | 0.0000128 | 3086 |
| Missense in Polyphen | 23 | 91.326 | 0.25184 | 1129 | ||
| Synonymous | 0.636 | 78 | 85.5 | 0.913 | 0.00000435 | 844 |
| Loss of Function | 4.01 | 0 | 18.7 | 0.00 | 9.61e-7 | 231 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 2.00 | 1.95 |
| Ashkenazi Jewish | 1.00 | 0.949 |
| East Asian | 1.00 | 0.956 |
| Finnish | 1.00 | 0.955 |
| European (Non-Finnish) | 1.00 | 0.942 |
| Middle Eastern | 1.00 | 0.956 |
| South Asian | 1.00 | 0.935 |
| Other | 1.00 | 0.935 |
dbNSFP
Source:
- Function
- FUNCTION: Transcriptional modulator activated by BMP (bone morphogenetic proteins) type 1 receptor kinase. SMAD5 is a receptor-regulated SMAD (R-SMAD).;
- Pathway
- TGF-beta signaling pathway - Homo sapiens (human);Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human);TGF-Core;Differentiation of white and brown adipocyte;BMP2-WNT4-FOXO1 Pathway in Human Primary Endometrial Stromal Cell Differentiation;BMP Signaling Pathway in Eyelid Development;ESC Pluripotency Pathways;Protein alkylation leading to liver fibrosis;TGF-beta Receptor Signaling;Signal Transduction;alk in cardiac myocytes;ctcf: first multivalent nuclear factor;TGF-beta super family signaling pathway canonical;BMP receptor signaling;BMP Signalling Pathway;BMP2 signaling TGF-beta MV;Signaling by BMP;Signaling by TGF-beta family members;BMP signaling Dro;ALK1 signaling events;ALK2 signaling events
(Consensus)
Recessive Scores
- pRec
- 0.240
Haploinsufficiency Scores
- pHI
- 0.908
- hipred
- Y
- hipred_score
- 0.728
- ghis
- 0.676
Essentials
- essential_gene_CRISPR
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.914
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Medium |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Smad5
- Phenotype
- skeleton phenotype; digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); 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); reproductive system phenotype; normal 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); neoplasm; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; craniofacial phenotype; growth/size/body region phenotype;
Zebrafish Information Network
- Gene name
- smad5
- Affected structure
- erythroid lineage cell
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;ureteric bud development;Mullerian duct regression;osteoblast fate commitment;protein phosphorylation;signal transduction;transforming growth factor beta receptor signaling pathway;germ cell development;embryonic pattern specification;erythrocyte differentiation;BMP signaling pathway;positive regulation of osteoblast differentiation;positive regulation of transcription, DNA-templated;cartilage development;cardiac muscle contraction;bone development;SMAD protein signal transduction;cellular response to organic cyclic compound;positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus
- Cellular component
- nucleus;nucleoplasm;transcription factor complex;cytoplasm;cytosol;protein-containing complex;SMAD protein complex
- Molecular function
- RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;protein binding;DEAD/H-box RNA helicase binding;transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity;ubiquitin protein ligase binding;metal ion binding