Pathway candidateNCBI-verifiedprotein-coding

SMAD4

SMAD family member 4

NCBI Gene: 4089 Ensembl GeneCards UniProt: Q13485

Pathway candidate — not linked to PFS or PSSD by any record here

SMAD4 is in the library because it belongs to the signaling & transcription family. No study, report or commentary in the corpus names it, so a variant in SMAD4 is not, by itself, evidence of anything related to post-drug syndromes.

Gene summary

A protein-coding gene on chromosome 18 (cell signaling and transcription factors). 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.

Source: NCBI Gene, accessed 2026-10-07.

Protein reference (UniProt)

Protein: SMAD family member 4
Function (excerpt): 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 pathway to promote hypertrophy via phosphorylated SMAD1/5/8. Acts synergistically with SMAD1 and YY1 in bone morphogenetic protein (BMP)-mediated cardiac-specific gene expression. Binds to SMAD binding elements (SBEs) (5'-GTCT/AGAC-3') within BMP response element (BMPRE) of cardiac activating regions (By similarity). Common SMAD (co-SMAD) is the coactivator and mediator of signal transduction by TGF-beta (transforming growth factor). Component of the heterotrimeric SMAD2/SMAD3-SMAD4 complex that forms in the nucleus and is required for the TGF-mediated signaling. Promotes binding of the SMAD2/SMAD4/FAST-1 complex to DNA and provides an activation function required for SMAD1 or SMAD2 to stimulate transcription.
Subcellular location: Cytoplasm; Nucleus.
Associated conditions: Pancreatic cancer (PNCA); Juvenile polyposis syndrome (JPS); Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome (JP/HHT); Colorectal cancer (CRC); Myhre syndrome (MYHRS).

Source: UniProtKB/Swiss-Prot Q13485, release 2026_03, licensed CC BY 4.0. This is the protein’s normal biology, not evidence about post-drug syndromes; associated conditions are inherited disorders of the gene, not PFS, PSSD or PRSD.

Why its pathway is in the library

General signaling/transcription machinery; no direct post-drug-syndrome link established for most members — included for completeness of the panel.

Written for the whole signaling & transcription family, not for SMAD4 specifically.

Mentioned in 0 corpus records

No corpus record names SMAD4 directly yet. It is in the library because it sits in a pathway the corpus tracks (Signaling & transcription).

Also in cell signaling and transcription factors

All 52 genes

Browse by family on the gene families page.

Gene summary

Source: NCBI Gene, accessed 2026-10-07.

Protein reference (UniProt)

Protein: SMAD family member 4
Function (excerpt): 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 pathway to promote hypertrophy via phosphorylated SMAD1/5/8. Acts synergistically with SMAD1 and YY1 in bone morphogenetic protein (BMP)-mediated cardiac-specific gene expression. Binds to SMAD binding elements (SBEs) (5'-GTCT/AGAC-3') within BMP response element (BMPRE) of cardiac activating regions (By similarity). Common SMAD (co-SMAD) is the coactivator and mediator of signal transduction by TGF-beta (transforming growth factor). Component of the heterotrimeric SMAD2/SMAD3-SMAD4 complex that forms in the nucleus and is required for the TGF-mediated signaling. Promotes binding of the SMAD2/SMAD4/FAST-1 complex to DNA and provides an activation function required for SMAD1 or SMAD2 to stimulate transcription.
Subcellular location: Cytoplasm; Nucleus.
Associated conditions: Pancreatic cancer (PNCA); Juvenile polyposis syndrome (JPS); Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome (JP/HHT); Colorectal cancer (CRC); Myhre syndrome (MYHRS).