FRMPD4

Chr X

FERM and PDZ domain containing 4

Also known as: MRX104, PDZD10, PDZK10, XLID104

NCBI Gene: 9758ENSG00000169933UniProt: Q14CM0

FRMPD4 encodes a multi-domain protein that positively regulates dendritic spine morphogenesis and density and is required for maintaining excitatory synaptic transmission. Mutations cause X-linked intellectual developmental disorder 104. This gene is extremely intolerant to loss-of-function variants, indicating it is highly constrained and critical for normal neuronal function.

ResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismLOEUF 0.08
Clinical Summary— FRMPD4
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Gene-Disease Validity (ClinGen)
X-linked complex neurodevelopmental disorder · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
38 unique Pathogenic / Likely Pathogenic· 312 VUS of 500 total submissions
Explore recent and relevant literature in Research Assistant →
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.08LOEUF
pLI 1.000
Z-score 5.54
OE 0.00 (0.00–0.08)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
1.95Z-score
OE missense 0.76 (0.70–0.83)
414 obs / 541.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.00–0.08)
0≤0.351.4
Missense OE0.76 (0.70–0.83)
0≤0.61.4
Synonymous OE1.13
0≤1.21.6
LoF obs/exp: 0 / 35.7Missense obs/exp: 414 / 541.7Syn Z: -1.61
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongFRMPD4-related intellectual disabilityLOFXLR
DN
0.2898th %ile
GOF
0.4974th %ile
LOF
0.79top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 39% of P/LP variants are LoF · LOEUF 0.08

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

500 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic26
Likely Pathogenic12
VUS312
Likely Benign75
Benign1
Conflicting6
26
Pathogenic
12
Likely Pathogenic
312
VUS
75
Likely Benign
1
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
0
23
0
26
Likely Pathogenic
12
0
0
0
12
VUS
2
286
19
5
312
Likely Benign
0
36
3
36
75
Benign
0
0
0
1
1
Conflicting
—6
Total173224542432

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

FRMPD4 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients