PLEKHM1

Chr 17q21.31

pleckstrin homology and RUN domain containing M1

Aliases:: KIAA0356
MANE:: ENST00000430334.8

OMIM: 611466 ↗NCBI: 9842 ↗Ensembl ↗

Annotations refreshed 9 hours ago.

Predicted protein structure

AlphaFold predicted structure

PLEKHM1 · Q9Y4G2

v62025-08-01

Predicted Aligned Error matrix for PLEKHM1 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

65.8/ 100

Low

1,056 residues

Confidence breakdown

Very high(≥ 90)31%
Confident(70–90)27%
Low(50–70)5%
Very low(< 50)37%

Open interactive 3D viewer

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

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

COVID-19 research
BIALLELIC, autosomal or pseudoautosomal
Osteopetrosis
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

osteopetrosis, autosomal dominant 3
0.52
autosomal recessive osteopetrosis 6
0.50
Intermediate osteopetrosis
0.50
autosomal dominant osteopetrosis
0.46
osteopetrosis
0.38
hypothyroidism
0.31
ovarian carcinoma
0.31
functional laterality
0.22
high grade ovarian serous adenocarcinoma
0.22
tinea unguium
0.21

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

Protein function (UniProt)

Pleckstrin homology domain-containing family M member 1

Acts as a multivalent adapter protein that regulates Rab7-dependent and HOPS complex-dependent fusion events in the endolysosomal system and couples autophagic and the endocytic trafficking pathways. Acts as a dual effector of RAB7A and ARL8B that simultaneously binds these GTPases, bringing about clustering and fusion of late endosomes and lysosomes (PubMed:25498145, PubMed:28325809). Required for late stages of endolysosomal maturation, facilitating both endocytosis-mediated degradation of growth factor receptors and autophagosome clearance. Interaction with Arl8b is a crucial factor in the terminal maturation of autophagosomes and to mediate autophagosome-lysosome fusion (PubMed:25498145). Positively regulates lysosome peripheral distribution and ruffled border formation in osteoclasts (By similarity). May be involved in negative regulation of endocytic transport from early endosome to late endosome/lysosome implicating its association with Rab7 (PubMed:20943950). May have a role in sialyl-lex-mediated transduction of apoptotic signals (PubMed:12820725). Involved in bone resorption (By similarity)