SMAD5

SMAD family member 5, the group of SMAD family

Basic information

Region (hg38): 5:136132844-136188747

Previous symbols: [ "MADH5" ]

Links

ENSG00000113658 ∙ NCBI:4090 ∙ OMIM:603110 ∙ HGNC:6771 ∙ Uniprot:Q99717 ∙ 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 SMAD5 gene.

• Inborn genetic diseases (6 variants)

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			6			6
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	6	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)
5-136161041-C-T		not specified	Uncertain significance (Mar 01, 2024)
5-136163293-A-G		not specified	Uncertain significance (Dec 01, 2023)
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: gnomAD

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: dbNSFP

• 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_CRISPR2: N
• 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