PDZD4

Chr X

PDZ domain containing 4

Also known as: LNX5, LU1, PDZK4, PDZRN4L

NCBI Gene: 57595 ENSG00000067840 UniProt: Q76G19 OMIM: 300634

The protein is predicted to be located in the cell cortex, though its specific function remains unclear. Mutations in PDZD4 cause autosomal recessive intellectual disability through a loss-of-function mechanism. The gene shows strong intolerance to loss-of-function variants, supporting its essential role in neurodevelopment.

OMIM ResearchSummary from RefSeq, Mechanism

Predicted to be located in cell cortex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.40

Clinical Summary— PDZD4

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.85) — some intolerance to loss-of-function variants.

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ClinVar Variants

79 VUS of 113 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.40LOEUF

pLI 0.849

Z-score 3.45

OE 0.15 (0.07–0.40)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.70Z-score

OE missense 0.61 (0.55–0.68)

239 obs / 389.1 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.15 (0.07–0.40)

0≤0.351.4

Missense OE?0.61 (0.55–0.68)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 3 / 19.4Missense obs/exp: 239 / 389.1Syn Z: 0.49

This gene — mechanism propensity

0.5771th %ile

GOF

0.6052th %ile

LOF

0.66top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.40

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

113 submitted variants in ClinVar

ClinVar

Classification Summary

VUS79

Likely Benign8

Conflicting1

VUS

Likely Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	1	78	0	0	79
Likely Benign	0	4	0	4	8
Benign	0	0	0	0	0
Conflicting	—				1
Total	1	82	0	4	88

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

View in ClinVar →

74 pathogenic / likely-pathogenic (of 87) ClinVar copy-number / structural variants overlap PDZD4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →