IRS4

Chr Xq22.3

insulin receptor substrate 4

Aliases:: PY160, IRS-4
MANE:: ENST00000372129.4

OMIM: 300904 ↗NCBI: 8471 ↗Ensembl ↗

Annotations refreshed 9 hours ago.

Predicted protein structure

AlphaFold predicted structure

IRS4 · O14654

v62025-08-01

Predicted Aligned Error matrix for IRS4 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

48.2/ 100

Very low

1,257 residues

Confidence breakdown

Very high(≥ 90)10%
Confident(70–90)9%
Low(50–70)7%
Very low(< 50)73%

Open interactive 3D viewer

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

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Congenital hypothyroidism
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Disease associations (Open Targets)

neurodegenerative disease
0.54
hypothyroidism, congenital, nongoitrous, 9
0.48
melanoma
0.39
central congenital hypothyroidism
0.37
lung adenocarcinoma
0.37
skin basal cell carcinoma
0.37
brain glioblastoma
0.37
endometrial endometrioid adenocarcinoma
0.37
colon adenocarcinoma
0.37
colorectal adenocarcinoma
0.37

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

Protein function (UniProt)

Insulin receptor substrate 4

Acts as an interface between multiple growth factor receptors possessing tyrosine kinase activity, such as insulin receptor, IGF1R and FGFR1, and a complex network of intracellular signaling molecules containing SH2 domains. Involved in the IGF1R mitogenic signaling pathway. Promotes the AKT1 signaling pathway and BAD phosphorylation during insulin stimulation without activation of RPS6KB1 or the inhibition of apoptosis. Interaction with GRB2 enhances insulin-stimulated mitogen-activated protein kinase activity. May be involved in nonreceptor tyrosine kinase signaling in myoblasts. Plays a pivotal role in the proliferation/differentiation of hepatoblastoma cell through EPHB2 activation upon IGF1 stimulation. May play a role in the signal transduction in response to insulin and to a lesser extent in response to IL4 and GH on mitogenesis. Plays a role in growth, reproduction and glucose homeostasis. May act as negative regulators of the IGF1 signaling pathway by suppressing the function of IRS1 and IRS2