FRMPD2

Chr 10

FERM and PDZ domain containing 2

Also known as: PDZD5C, PDZK4, PDZK5C

The protein encoded by this gene functions as a scaffold protein involved in NMDA receptor-mediated synaptic transmission and regulation of tight junction formation, while also playing roles in synapse formation in cone photoreceptor cells. Mutations cause autosomal recessive intellectual disability with epilepsy and abnormal behavior, typically presenting in early childhood. This gene shows minimal constraint against loss-of-function variants based on population genetics data.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
1
Pubs (1 yr)
58
P/LP submissions
0%
P/LP missense
1.18
LOEUF
GOF
Mechanism· predicted
Clinical SummaryFRMPD2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
58 unique Pathogenic / Likely Pathogenic· 194 VUS of 293 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.18LOEUF
pLI 0.000
Z-score 0.47
OE 0.93 (0.741.18)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.75Z-score
OE missense 1.09 (1.021.16)
625 obs / 574.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.93 (0.741.18)
00.351.4
Missense OE1.09 (1.021.16)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 51 / 54.7Missense obs/exp: 625 / 574.4Syn Z: -1.26
DN
0.5575th %ile
GOF
0.6639th %ile
LOF
0.4825th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction 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

293 submitted variants in ClinVar

Classification Summary

Pathogenic37
Likely Pathogenic21
VUS194
Likely Benign27
Benign4
37
Pathogenic
21
Likely Pathogenic
194
VUS
27
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
37
0
37
Likely Pathogenic
0
0
21
0
21
VUS
0
165
29
0
194
Likely Benign
0
16
3
8
27
Benign
0
2
2
0
4
Total0183928283

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

View in ClinVar →

Protein Context — Lollipop Plot

FRMPD2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC