PCDH20

Chr 13

protocadherin 20

Also known as: PCDH13

NCBI Gene: 64881 ENSG00000280165 UniProt: Q8N6Y1

The protein is a potential calcium-dependent cell-adhesion protein containing 6 extracellular cadherin domains that is thought to establish and maintain specific cell-cell connections in the brain. Mutations cause autosomal recessive developmental and epileptic encephalopathy with microcephaly, affecting neurological development. The gene is highly constrained against loss-of-function variants (pLI 0.86, LOEUF 0.38), indicating intolerance to protein-disrupting mutations.

ResearchSummary from RefSeq, UniProt

This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. This gene encodes a protein which contains 6 extracellular cadherin domains, a transmembrane domain and a cytoplasmic tail differing from those of the classical cadherins. Although its specific function is undetermined, the cadherin-related neuronal receptor is thought to play a role in the establishment and function of specific cell-cell connections in the brain. [provided by RefSeq, Jul 2008]

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

0.38

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.38LOEUF

pLI 0.862

Z-score 3.79

OE 0.17 (0.08–0.38)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.71Z-score

OE missense 0.91 (0.84–0.98)

456 obs / 500.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.17 (0.08–0.38)

0≤0.351.4

Missense OE?0.91 (0.84–0.98)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 4 / 24.1Missense obs/exp: 456 / 500.4Syn Z: -0.89

Background carrier burden — how many people carry a rare variant somewhere in PCDH20?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 58

1,245 rare PASS variants

Rare truncating (LoF)

1 in 2,200

96 rare PASS variants

Rare synonymous (reference)

1 in 130

538 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PCDH20. 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 89	1 in 2,000
South Asian	~43k	1 in 38	1 in 5,900
Remaining (unassigned)	~30k	1 in 50	1 in 2,100
European (Finnish)	~27k	1 in 130	1 in 840
Admixed American	~22k	1 in 56	1 in 1,900
African / African American	~21k	1 in 57	1 in 650
East Asian	~20k	1 in 61	1 in 450
Ashkenazi Jewish	~13k	1 in 140	1 in 630
Middle Eastern	~2,884	1 in 84	≈ 1 in 1,300

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): 1 of 2 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 2.? see exons ↓