PDZD8

Chr 10AR

PDZ domain containing 8

Also known as: IDDADF, LYVAC, PDZK8

NCBI Gene: 118987 ENSG00000165650 UniProt: Q8NEN9 OMIM: 614235

Predicted to enable lipid binding activity and zinc ion binding activity. Involved in mitochondrial calcium ion homeostasis and mitochondrion-endoplasmic reticulum membrane tethering. Located in endoplasmic reticulum membrane and mitochondria-associated endoplasmic reticulum membrane contact site. [provided by Alliance of Genome Resources, Jun 2026]

OMIM Research

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Intellectual developmental disorder with autism and dysmorphic faciesMIM #620021

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Intellectual developmental disorder with autism and dysmorphic facies; no ClinGen or GenCC tier

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

0.20

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.20LOEUF

pLI 1.000

Z-score 5.27

OE 0.08 (0.04–0.20)

Highly constrained

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

Missense Constraint?

1.57Z-score

OE missense 0.82 (0.76–0.89)

512 obs / 622.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.08 (0.04–0.20)

0≤0.351.4

Missense OE?0.82 (0.76–0.89)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 3 / 38.2Missense obs/exp: 512 / 622.4Syn Z: -0.61

Background carrier burden — how many people carry a rare variant somewhere in PDZD8?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 64

1,273 rare PASS variants

Rare truncating (LoF)

1 in 4,700

58 rare PASS variants

Rare synonymous (reference)

1 in 120

632 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PDZD8. 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 87	1 in 4,200
South Asian	~43k	1 in 64	1 in 8,600
Remaining (unassigned)	~30k	1 in 69	none seen
European (Finnish)	~27k	1 in 150	≈ 1 in 8,900
Admixed American	~22k	1 in 41	≈ 1 in 4,500
African / African American	~21k	1 in 57	1 in 3,900
East Asian	~20k	1 in 55	none seen
Ashkenazi Jewish	~13k	1 in 270	none seen
Middle Eastern	~2,884	1 in 51	none seen

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): All 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓