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FRMPD4
FERM and PDZ domain containing 4
FRMPD4 is located on the short (p) arm of chromosome X, at band Xp22.2. Arm ratio per GRCh38 - banding schematic.
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Overview
FRMPD4 (FERM and PDZ domain containing 4) is a gene situated on the X chromosome that encodes a protein carrying two conserved structural modules: a FERM domain and a PDZ domain. These domains are commonly found in scaffolding proteins that anchor signalling molecules to the cell membrane and cytoskeleton, facilitating organised cellular responses.
The gene's position on the X chromosome means that inheritance patterns may differ between males and females, with males possessing only one copy and females carrying two. Research into FRMPD4 is ongoing, and the full spectrum of its physiological roles and associated clinical phenotypes has not yet been comprehensively defined.
What the gene does
The FRMPD4 protein is predicted to function as a molecular scaffold, bringing together different signalling proteins within the cell. FERM domains typically mediate attachment to the plasma membrane by binding phospholipids and linking membrane proteins to the cytoskeleton. PDZ domains recognise short amino acid sequences at the ends of other proteins, enabling the assembly of multi-protein complexes at specific cellular locations.
By combining these two domain types, FRMPD4 may coordinate the spatial organisation of signalling pathways, particularly those involved in cell adhesion, polarity, or communication between cells. The protein's precise biochemical partners and the cellular processes it regulates remain areas of active investigation. Understanding these interactions will clarify how FRMPD4 contributes to normal cellular function and whether disruptions lead to specific disease states.
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Chromosome location
FRMPD4 is located on the short arm of the X chromosome at band Xp22.2. This region of the X chromosome contains numerous genes, and variants in this chromosomal segment have been associated with various developmental and neurological conditions.
The gene's X-chromosomal location influences how variants are inherited and expressed. Males inherit only one X chromosome, so a single variant in FRMPD4 will be expressed without a second copy to compensate. Females carry two X chromosomes and may show variable expression depending on random X-inactivation patterns in different tissues.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein. The gene name indicates the predicted presence of FERM and PDZ domains based on sequence analysis, but specific boundaries, functional validation, and structural studies have not been comprehensively reported in the scientific literature. Further research is needed to confirm the protein's domain organisation and how these regions contribute to its cellular roles.
Key variants
Genetic variants in FRMPD4 encompass single-nucleotide changes, small insertions or deletions, and potentially larger structural alterations. The clinical significance of most variants has not been established, reflecting the early stage of research into this gene's role in human health.
As with other X-linked genes, the impact of FRMPD4 variants may differ between males and females. Males carrying a pathogenic variant typically express the altered protein exclusively, whereas females may exhibit milder or variable features depending on which X chromosome is active in different cells.
Sample of pathogenic variants
8 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
g.(12157132_12516798)_(12704324_12708313)del | - | Pathogenic | ★☆☆☆ | Intellectual disability, X-linked 104 |
c.1411G>T | p.Glu471Ter | Pathogenic | ★☆☆☆ | Intellectual disability, X-linked 104 |
c.2776del | p.Gln926fs | Pathogenic | ★☆☆☆ | not provided |
c.3145C>T | p.Gln1049Ter | Pathogenic | ★☆☆☆ | not provided |
c.856C>T | p.Arg286Ter | Pathogenic | ★☆☆☆ | Intellectual disability, X-linked 104 |
c.933+1G>A | - | Pathogenic | ★☆☆☆ | not provided |
g.12515801_12581900del | - | Pathogenic | - | Intellectual disability, X-linked 104 |
c.1851del | p.Cys618fs | Pathogenic | - | Intellectual disability, X-linked 104 |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
No specific inherited conditions have been definitively linked to FRMPD4 variants in large-scale clinical studies to date. The gene is not currently included in diagnostic panels for well-characterised genetic syndromes.
Research publications have suggested potential associations with neurodevelopmental or behavioural phenotypes, but these findings require replication in independent cohorts. As our understanding of rare X-linked disorders expands, future studies may clarify whether FRMPD4 variants contribute to recognisable clinical presentations and what the penetrance and expressivity of such variants might be.
No disease links recorded for this gene in our reference set.
UK clinical status
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
Why is FRMPD4 located on the X chromosome significant?
X-chromosomal location means males have only one copy of FRMPD4, so variants are always expressed. Females carry two copies and may show variable effects due to random X-inactivation, where one X chromosome is silenced in each cell.
What do FERM and PDZ domains do in proteins?
FERM domains typically anchor proteins to cell membranes and link them to the cytoskeleton. PDZ domains bind specific sequences on other proteins, assembling multi-protein complexes that coordinate cellular signalling and structural organisation.
Are there established medical conditions linked to FRMPD4?
No specific inherited conditions have been definitively associated with FRMPD4 variants in large clinical studies. The gene's role in human health is still being investigated, and it is not currently part of routine diagnostic testing panels.