MADD

Chr 11p11.2

MAP kinase activating death domain

Aliases:: DENN, KIAA0358, RAB3GEP, IG20
MANE:: ENST00000706887.1

OMIM: 603584 ↗NCBI: 8567 ↗Ensembl ↗

Annotations refreshed 10 hours ago.

Predicted protein structure

AlphaFold predicted structure

MADD · Q8WXG6

v62025-08-01

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

Mean pLDDT

63.4/ 100

Low

1,647 residues

Confidence breakdown

Very high(≥ 90)26%
Confident(70–90)25%
Low(50–70)8%
Very low(< 50)41%

Open interactive 3D viewer

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

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

DDG2P
BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy
BIALLELIC, autosomal or pseudoautosomal
Intellectual disability
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

neurodevelopmental disorder with dysmorphic facies, impaired speech, and hypotonia
0.79
deeah syndrome
0.78
hereditary disease
0.49
hypertensive disorder
0.44
complex neurodevelopmental disorder
0.37
glaucoma
0.35
multiple acyl-CoA dehydrogenase deficiency, severe neonatal type
0.34
neurodegenerative disease
0.34
venous thromboembolism
0.31
essential hypertension
0.28

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

Protein function (UniProt)

MAP kinase-activating death domain protein

Guanyl-nucleotide exchange factor that regulates small GTPases of the Rab family (PubMed:18559336, PubMed:20937701). Converts GDP-bound inactive form of RAB27A and RAB27B to the GTP-bound active forms (PubMed:18559336, PubMed:20937701). Converts GDP-bound inactive form of RAB3A, RAB3C and RAB3D to the GTP-bound active forms, GTPases involved in synaptic vesicle exocytosis and vesicle secretion (By similarity). Plays a role in synaptic vesicle formation and in vesicle trafficking at the neuromuscular junction (By similarity). Involved in up-regulating a post-docking step of synaptic exocytosis in central synapses (By similarity). Probably by binding to the motor proteins KIF1B and KIF1A, mediates motor-dependent transport of GTP-RAB3A-positive vesicles to the presynaptic nerve terminals (By similarity). Plays a role in TNFA-mediated activation of the MAPK pathway, including ERK1/2 (PubMed:32761064). May link TNFRSF1A with MAP kinase activation (PubMed:9115275). May be involved in the regulation of TNFA-induced apoptosis (PubMed:11577081, PubMed:32761064)