PKP4

Chr 2

plakophilin 4

Also known as: p0071

NCBI Gene: 8502 ENSG00000144283 UniProt: Q99569 OMIM: 604276

Armadillo-like proteins are characterized by a series of armadillo repeats, first defined in the Drosophila 'armadillo' gene product, that are typically 42 to 45 amino acids in length. These proteins can be divided into subfamilies based on their number of repeats, their overall sequence similarity, and the dispersion of the repeats throughout their sequences. Members of the p120(ctn)/plakophilin subfamily of Armadillo-like proteins, including CTNND1, CTNND2, PKP1, PKP2, PKP4, and ARVCF. PKP4 may be a component of desmosomal plaque and other adhesion plaques and is thought to be involved in regulating junctional plaque organization and cadherin function. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2015]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.64

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.64LOEUF

pLI 0.000

Z-score 3.97

OE 0.48 (0.36–0.64)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.97Z-score

OE missense 0.90 (0.84–0.96)

613 obs / 684.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.48 (0.36–0.64)

0≤0.351.4

Missense OE?0.90 (0.84–0.96)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 32 / 67.1Missense obs/exp: 613 / 684.6Syn Z: 0.38

Background carrier burden — how many people carry a rare variant somewhere in PKP4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 41

1,441 rare PASS variants

Rare truncating (LoF)

1 in 930

207 rare PASS variants

Rare synonymous (reference)

1 in 71

616 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PKP4. 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 52	1 in 1,100
South Asian	~43k	1 in 37	1 in 410
Remaining (unassigned)	~30k	1 in 35	1 in 2,300
European (Finnish)	~27k	1 in 120	1 in 3,300
Admixed American	~22k	1 in 29	1 in 1,000
African / African American	~21k	1 in 40	1 in 300
East Asian	~20k	1 in 36	1 in 1,300
Ashkenazi Jewish	~13k	1 in 95	1 in 2,600
Middle Eastern	~2,884	1 in 48	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): 16 of 21 coding exons well covered in gnomAD exomes; exons 4, 12, 13, 19, 21 marginal. Genomes: all 21.? see exons ↓