FEM1B

Chr 15q23

fem-1 homolog B

MANE:: ENST00000306917.5

OMIM: 613539 ↗NCBI: 10116 ↗Ensembl ↗

Annotations refreshed 9 hours ago.

Predicted protein structure

AlphaFold predicted structure

FEM1B · Q9UK73

v62025-08-01

Predicted Aligned Error matrix for FEM1B — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

94.4/ 100

Very high

627 residues

Confidence breakdown

Very high(≥ 90)84%
Confident(70–90)15%
Low(50–70)1%
Very low(< 50)0%

Open interactive 3D viewer

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

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

DDG2P
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Disease associations (Open Targets)

neurodevelopmental disorder with behavioral, ear, and skeletal abnormalities
0.59
neurodevelopmental disorder
0.37
Intellectual disability
0.37
malignant renal pelvis neoplasm
0.25
hypospadias
0.06
diabetes mellitus
0.05
diabetic ketoacidosis
0.05
acute lymphoblastic leukemia
0.05
hypospadias 2, X-linked
0.05
exercise-induced hyperinsulinism
0.04

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

Protein function (UniProt)

Protein fem-1 homolog B

Substrate-recognition component of a Cul2-RING (CRL2) E3 ubiquitin-protein ligase complex of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation (PubMed:29779948, PubMed:33398168, PubMed:33398170). The C-degron recognized by the DesCEND pathway is usually a motif of less than ten residues and can be present in full-length proteins, truncated proteins or proteolytically cleaved forms (PubMed:29779948, PubMed:33398168, PubMed:33398170). The CRL2(FEM1B) complex specifically recognizes proteins ending with -Gly-Leu-Asp-Arg, such as CDK5R1, leading to their ubiquitination and degradation (PubMed:33398168, PubMed:33398170). Also acts as a regulator of the reductive stress response by mediating ubiquitination of reduced FNIP1: in response to reductive stress, the CRL2(FEM1B) complex specifically recognizes a conserved Cys degron in FNIP1 when this degron is reduced, leading to FNIP1 degradation and subsequent activation of mitochondria to recalibrate reactive oxygen species (ROS) (By similarity). Mechanistically, recognizes and binds reduced FNIP1 through two interface zinc ions, which act as a molecular glue that recruit reduced FNIP1 to FEM1B (By similarity). Promotes ubiquitination of GLI1, suppressing GLI1 transcriptional activator activity (PubMed:24076122). Promotes ubiquitination and degradation of ANKRD37 (By similarity). Promotes ubiquitination and degradation of SLBP (PubMed:28118078). Involved in apoptosis by acting as a death receptor-associated protein that mediates apoptosis (PubMed:10542291). Also involved in glucose homeostasis in pancreatic islet (By similarity). May also act as an adapter/mediator in replication stress-induced signaling that leads to the activation of CHEK1 (PubMed:19330022)