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…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.42

LOEUF

GOF

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in PDLIM7?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 40

943 rare PASS variants

Rare truncating (LoF)

1 in 820

153 rare PASS variants

Rare synonymous (reference)

1 in 99

307 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PDLIM7. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 48	1 in 830
South Asian	~43k	1 in 57	1 in 630
Remaining (unassigned)	~30k	1 in 41	1 in 1,400
European (Finnish)	~27k	1 in 130	1 in 1,500
Admixed American	~22k	1 in 48	1 in 1,800
African / African American	~21k	1 in 48	1 in 410
East Asian	~20k	1 in 45	1 in 250
Ashkenazi Jewish	~13k	1 in 760	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 41	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 11 of 12 coding exons well covered in gnomAD exomes; exon 5 marginal. Genomes: all 12.? see exons ↓