PDLIM4

Chr 5AD

PDZ and LIM domain 4

Also known as: RIL

NCBI Gene: 8572 ENSG00000131435 UniProt: P50479 OMIM: 603422

Enables alpha-actinin binding activity; protein homodimerization activity; and protein phosphatase binding activity. Involved in actin cytoskeleton organization. Located in several cellular components, including lamellipodium; perinuclear region of cytoplasm; and stress fiber. Part of filamentous actin. Implicated in osteoporosis. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Osteoporosis, susceptibility to}MIM #166710

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

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.24

LOEUF· LoF intol.

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.24LOEUF

pLI 0.983

Z-score 3.26

OE 0.00 (0.00–0.24)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

0.71Z-score

OE missense 0.86 (0.77–0.97)

186 obs / 215.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.24)

0≤0.351.4

Missense OE?0.86 (0.77–0.97)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 0 / 12.4Missense obs/exp: 186 / 215.5Syn Z: 0.53

Background carrier burden — how many people carry a rare variant somewhere in PDLIM4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 180

485 rare PASS variants

Rare truncating (LoF)

1 in 3,300

65 rare PASS variants

Rare synonymous (reference)

1 in 310

172 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PDLIM4. 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 220	1 in 5,200
South Asian	~43k	1 in 200	1 in 7,000
Remaining (unassigned)	~30k	1 in 170	1 in 2,700
European (Finnish)	~27k	1 in 730	≈ 1 in 8,200
Admixed American	~22k	1 in 130	1 in 920
African / African American	~21k	1 in 120	≈ 1 in 4,900
East Asian	~20k	1 in 170	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 1,300	≈ 1 in 6,200
Middle Eastern	~2,884	1 in 83	≈ 1 in 2,900

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): 6 of 7 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 7.? see exons ↓