FRMD3

Chr 9

FERM domain containing 3

The protein encoded by FRMD3 is a single-pass membrane protein with undetermined function, though it may act as a tumor suppressor. Based on current evidence, pathogenic variants have not been definitively associated with pediatric neurological disorders, despite some linkage to diabetic nephropathy susceptibility in type 1 diabetes.

OMIMResearchSummary from RefSeq, UniProt, Mechanism
MultiplemechanismLOEUF 0.44
Clinical SummaryFRMD3
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.44LOEUF
pLI 0.270
Z-score 3.87
OE 0.24 (0.130.44)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.88Z-score
OE missense 0.86 (0.780.95)
267 obs / 310.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.24 (0.130.44)
00.351.4
Missense OE0.86 (0.780.95)
00.61.4
Synonymous OE1.24
01.21.6
LoF obs/exp: 7 / 29.8Missense obs/exp: 267 / 310.6Syn Z: -2.01
DN
0.6746th %ile
GOF
0.6735th %ile
LOF
0.3452th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

FRMD3 · 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

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗