SMAD5

Chr 5q31.1

SMAD family member 5

Aliases:: Dwfc, JV5-1
MANE:: ENST00000545279.6

OMIM: 603110 ↗NCBI: 4090 ↗Ensembl ↗

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Predicted protein structure

AlphaFold predicted structure

SMAD5 · Q99717

v62025-08-01

Predicted Aligned Error matrix for SMAD5 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

80.9/ 100

Confident

465 residues

Confidence breakdown

Very high(≥ 90)64%
Confident(70–90)12%
Low(50–70)3%
Very low(< 50)21%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Moderate Evidence (Amber)

Fetal anomalies
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Disease associations (Open Targets)

neurodegenerative disease
0.23
congenital heart disease
0.23
benign prostatic hyperplasia
0.17
insomnia
0.15
gastric cancer
0.09
nasopharyngeal carcinoma
0.09
neoplasm
0.08
keloid
0.08
chronic myelogenous leukemia, BCR-ABL1 positive
0.08
pulmonary arterial hypertension
0.07

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

SMAD family member 5

Transcriptional regulator that plays a role in various cellular processes including embryonic development, cell differentiation, angiogenesis and tissue homeostasis (PubMed:12064918, PubMed:16516194). Upon BMP ligand binding to their receptors at the cell surface, is phosphorylated by activated type I BMP receptors (BMPRIs) and associates with SMAD4 to form a heteromeric complex which translocates into the nucleus acting as transcription factor (PubMed:9442019). In turn, the hetero-trimeric complex recognizes cis-regulatory elements containing Smad Binding Elements (SBEs) to modulate the outcome of the signaling network (PubMed:33510867). Non-phosphorylated SMAD5 has a cytoplasmic role in energy metabolism regulation by promoting mitochondrial respiration and glycolysis in response to cytoplasmic pH changes (PubMed:28675158). Mechanistically, interacts with hexokinase 1/HK1 and thereby accelerates glycolysis (PubMed:28675158)