PDLIM7

Chr 5

PDZ and LIM domain 7

Also known as: LMP1, LMP3

The protein contains PDZ and LIM domains that function as a scaffold for protein assembly, with the PDZ domain binding actin filaments and LIM domains binding protein kinases to coordinate cytoskeletal interactions and signaling pathways including BMP6 signaling essential for bone formation. Mutations cause autosomal recessive peripheral neuropathy with or without impaired intellectual development, affecting both the nervous system and skeletal development. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.425), indicating evolutionary intolerance to complete protein loss.

Summary from RefSeq, UniProt
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3
Active trials
6
Pubs (1 yr)
58
P/LP submissions
0%
P/LP missense
0.42
LOEUF
GOF
Mechanism· predicted
Clinical SummaryPDLIM7
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.71) — some intolerance to loss-of-function variants.
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ClinVar Variants
56 unique Pathogenic / Likely Pathogenic· 80 VUS of 168 total submissions
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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.42LOEUF
pLI 0.708
Z-score 3.50
OE 0.19 (0.090.42)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.73Z-score
OE missense 0.88 (0.790.97)
247 obs / 281.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.19 (0.090.42)
00.351.4
Missense OE0.88 (0.790.97)
00.61.4
Synonymous OE1.15
01.21.6
LoF obs/exp: 4 / 21.6Missense obs/exp: 247 / 281.5Syn Z: -1.26
DN
0.5967th %ile
GOF
0.6737th %ile
LOF
0.56top 25%

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

168 submitted variants in ClinVar

Classification Summary

Pathogenic51
Likely Pathogenic5
VUS80
Likely Benign4
Benign6
51
Pathogenic
5
Likely Pathogenic
80
VUS
4
Likely Benign
6
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
51
0
51
Likely Pathogenic
0
0
5
0
5
VUS
0
69
11
0
80
Likely Benign
0
1
1
2
4
Benign
0
0
1
5
6
Total070697146

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

View in ClinVar →

Protein Context — Lollipop Plot

PDLIM7 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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