PDLIM7

Chr 5

PDZ and LIM domain 7

Also known as: LMP1, LMP3

NCBI Gene: 9260 ENSG00000196923 UniProt: Q9NR12 OMIM: 605903

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.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is representative of a family of proteins composed of conserved PDZ and LIM domains. LIM domains are proposed to function in protein-protein recognition in a variety of contexts including gene transcription and development and in cytoskeletal interaction. The LIM domains of this protein bind to protein kinases, whereas the PDZ domain binds to actin filaments. The gene product is involved in the assembly of an actin filament-associated complex essential for transmission of ret/ptc2 mitogenic signaling. The biological function is likely to be that of an adapter, with the PDZ domain localizing the LIM-binding proteins to actin filaments of both skeletal muscle and nonmuscle tissues. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

GOFmechanismLOEUF 0.42

Clinical Summary— PDLIM7

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.71) — some intolerance to loss-of-function variants.

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ClinVar Variants

69 VUS of 100 total submissions

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Clinical Trials

3 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.42LOEUF

pLI 0.708

Z-score 3.50

OE 0.19 (0.09–0.42)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.73Z-score

OE missense 0.88 (0.79–0.97)

247 obs / 281.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.19 (0.09–0.42)

0≤0.351.4

Missense OE?0.88 (0.79–0.97)

0≤0.61.4

Synonymous OE?1.15

0≤1.21.6

LoF obs/exp: 4 / 21.6Missense obs/exp: 247 / 281.5Syn Z: -1.26

This gene — mechanism propensity

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

100 submitted variants in ClinVar

ClinVar

Classification Summary

VUS69

Likely Benign3

Benign6

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	69	0	0	69
Likely Benign	1	0	2	3
Benign	0	1	5	6
Total	70	1	7	78

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

View in ClinVar →

58 pathogenic / likely-pathogenic (of 70) ClinVar copy-number / structural variants overlap PDLIM7 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →