Gene Gene information from NCBI Gene database.
Entrez ID 4089
Gene name SMAD family member 4
Gene symbol SMAD4
Synonyms (NCBI Gene)
DPC4JIPMADH4MYHRS
Chromosome 18
Chromosome location 18q21.2
Summary This gene encodes a member of the Smad family of signal transduction proteins. Smad proteins are phosphorylated and activated by transmembrane serine-threonine receptor kinases in response to transforming growth factor (TGF)-beta signaling. The product of
SNPs SNP information provided by dbSNP.
178
SNP ID Visualize variation Clinical significance Consequence
rs7238500 A>G Likely-benign, conflicting-interpretations-of-pathogenicity, uncertain-significance Missense variant, coding sequence variant
rs80338963 C>A,G,T Not-provided, pathogenic, likely-pathogenic Coding sequence variant, missense variant
rs80338964 C>T Pathogenic Stop gained, coding sequence variant
rs80338965 CAGA>- Pathogenic Coding sequence variant, frameshift variant
rs121912576 G>T Pathogenic Stop gained, coding sequence variant
miRNA miRNA information provided by mirtarbase database.
1103
miRTarBase ID miRNA Experiments Reference
MIRT004736 hsa-miR-18a-5p ImmunoblotLuciferase reporter assayMicroarrayqRT-PCRWestern blot 20940405
MIRT004118 hsa-miR-483-3p Luciferase reporter assayqRT-PCRWestern blot 21112326
MIRT004118 hsa-miR-483-3p Luciferase reporter assayqRT-PCRWestern blot 21112326
MIRT004118 hsa-miR-483-3p Luciferase reporter assayqRT-PCRWestern blot 21112326
MIRT004118 hsa-miR-483-3p Luciferase reporter assayqRT-PCRWestern blot 21112326
Transcription factors Transcription factors information provided by TRRUST V2 database.
5
Transcription factor Regulation Reference
FOS Unknown 11854297
GLI1 Unknown 24739390
HDAC4 Unknown 23817620
JUNB Unknown 11854297
KAT2B Activation 19525977
Gene ontology (GO) Gene Ontology (GO) annotations describing the biological processes, molecular functions, and cellular components associated with a gene.
193
GO ID Ontology Definition Evidence Reference
GO:0000122 Process Negative regulation of transcription by RNA polymerase II IEA
GO:0000122 Process Negative regulation of transcription by RNA polymerase II ISS
GO:0000785 Component Chromatin IDA 21828274
GO:0000785 Component Chromatin ISA
GO:0000976 Function Transcription cis-regulatory region binding IDA 17438144
Other IDs Other IDs provides unique identifiers for this gene in OMIM, HGNC, and Ensembl databases.
MIM HGNC e!Ensembl
600993 6770 ENSG00000141646
Protein Protein information from UniProt database.
UniProt ID Unique identifier for the protein in the UniProt database. Click to view detailed protein information.
Q13485
Protein name Mothers against decapentaplegic homolog 4 (MAD homolog 4) (Mothers against DPP homolog 4) (Deletion target in pancreatic carcinoma 4) (SMAD family member 4) (SMAD 4) (Smad4) (hSMAD4)
Protein function In muscle physiology, plays a central role in the balance between atrophy and hypertrophy. When recruited by MSTN, promotes atrophy response via phosphorylated SMAD2/4. MSTN decrease causes SMAD4 release and subsequent recruitment by the BMP pat
PDB 1DD1 , 1G88 , 1MR1 , 1U7F , 1U7V , 1YGS , 5C4V , 5MEY , 5MEZ , 5MF0 , 5UWU , 6YIC
Family and domains

Pfam

Accession ID Position in sequence Description Type
PF03165 MH1 36 137 MH1 domain Domain
PF03166 MH2 321 530 MH2 domain Family
Sequence
MDNMSITNTPTSNDACLSIVHSLMCHRQGGESETFAKRAIESLVKKLKEKKDELDSLITA
ITTNGAHPSKCVTIQRTLDGRLQVAGRKGFPHVIYARLWRWPDLHKNELKHVKYCQYAFD
LKCDSVCVNPYHYERVV
SPGIDLSGLTLQSNAPSSMMVKDEYVHDFEGQPSLSTEGHSIQ
TIQHPPSNRASTETYSTPALLAPSESNATSTANFPNIPVASTSQPASILGGSHSEGLLQI
ASGPQPGQQQNGFTGQPATYHHNSTTTWTGSRTAPYTPNLPHHQNGHLQHHPPMPPHPGH
YWPVHNELAFQPPISNHPAPEYWCSIAYFEMDVQVGETFKVPSSCPIVTVDGYVDPSGGD
RFCLGQLSNVHRTEAIERARLHIGKGVQLECKGEGDVWVRCLSDHAVFVQSYYLDREAGR
APGDAVHKIYPSAYIKVFDLRQCHRQMQQQAATAQAAAAAQAAAVAGNIPGPGSVGGIAP
AISLSAAAGIGVDDLRRLCILRMSFVKGWGPDYPRQSIKETPCWIEIHLH
RALQLLDEVL
HTMPIADPQPLD
Sequence length 552
Interactions View interactions
Associated diseases Disease associations from ClinVar (causal & non-causal) and other databases (OMIM, Orphanet, GWAS, etc.).
73
Evidence Score: ★☆☆☆☆  Gene-disease association found in Text Mining only ★★☆☆☆  Found in Text Mining and Unknown/Other Associations ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants) ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)
Causal Diseases associated with Pathogenic or Likely Pathogenic variants in ClinVar
Phenotype Name Clinical Significance dbSNP ID RCV Accession Evidence Score
Abnormal bleeding Pathogenic rs771084683 RCV001270577
★★★★☆
ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Carcinoma of colon Pathogenic rs2144427253, rs80338965 RCV001358302
RCV001357425
★★★★☆
ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Carcinoma of pancreas Pathogenic; Likely pathogenic rs80338965, rs121912576, rs121912578, rs121912579, rs377767347, rs121912577, rs281875322, rs397518413 RCV000768095
RCV000009062
RCV000009064
RCV000009065
RCV000763030
View all (3 more)
★★★★★
ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Colorectal cancer Pathogenic; Likely pathogenic rs2144446385, rs80338964, rs377767347, rs1599195400, rs1910183166 RCV006250185
RCV006250161
RCV006253678
RCV006250180
RCV001293846
★★★★★
ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Unknown / Other Associations ClinVar entries with uncertain/conflicting evidence, and associations from other databases (OMIM, Orphanet, GWAS, etc.) where the gene is not established as causal.
Phenotype Name Clinical Significance Source Evidence Score
Acute myeloid leukemia Benign; Uncertain significance ClinVar
★★☆☆☆
Found in Text Mining + Unknown/Other Associations
AORTIC DISEASES Disgenet
★★☆☆☆
Found in Text Mining + Unknown/Other Associations
ASTHMA GWAS catalog
★★☆☆☆
Found in Text Mining + Unknown/Other Associations
ATRIAL FIBRILLATION GWAS catalog
★★☆☆☆
Found in Text Mining + Unknown/Other Associations
Associations from Text Mining Disease associations identified through text mining
Disease Name Disease (Merged) Source PMID Relationship Type Evidence Score
2-3 toe syndactyly Syndactyly Of The Toes HPO_DG
★☆☆☆☆
Found in Text Mining only
Actinic keratosis Actinic keratosis BEFREE 22301403, 23648546
★☆☆☆☆
Found in Text Mining only
Acute intermittent porphyria Intermittent Porphyria BEFREE 24457081
★☆☆☆☆
Found in Text Mining only
Acute monocytic leukemia Monocytic Leukemia BEFREE 12443883
★☆☆☆☆
Found in Text Mining only
Acute Promyelocytic Leukemia Promyelocytic Leukemia BEFREE 25161335
★☆☆☆☆
Found in Text Mining only
Adenocarcinoma Adenocarcinoma BEFREE 10408907, 10415848, 10623651, 10626800, 10980115, 11323508, 11751510, 12429655, 12640108, 12720172, 14647445, 14669329, 15157044, 15736060, 15855639
View all (21 more)
★☆☆☆☆
Found in Text Mining only
Adenocarcinoma Adenocarcinoma LHGDN 12720172, 14647445, 15157044, 15367885, 15736060, 17854080, 19064568
★☆☆☆☆
Found in Text Mining only
Adenocarcinoma of colon Adenocarcinoma Of Colon BEFREE 15063137, 25742737, 29673545
★☆☆☆☆
Found in Text Mining only
Adenocarcinoma Of Esophagus Esophageal Cancer BEFREE 16368780, 8813122
★☆☆☆☆
Found in Text Mining only
Adenocarcinoma Of Esophagus Esophageal Cancer CTD_human_DG 23525077, 24952744
★☆☆☆☆
Found in Text Mining only