PRR14

Chr 16

proline rich 14

NCBI Gene: 78994 ENSG00000156858 UniProt: Q9BWN1 OMIM: 617423

This protein tethers heterochromatin to the nuclear lamina during interphase and promotes skeletal muscle differentiation by stimulating MyoD transcription factor activity. PRR14 mutations cause autosomal recessive intellectual disability with hypotonia and poor growth, with affected individuals showing developmental delays from infancy. The gene is highly constrained against loss-of-function variants, indicating intolerance to protein-disrupting mutations.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene tethers heterochromatin to the nuclear laminar scaffold by binding heterochromatin protein 1 (HP1) and the nuclear lamina. The tether is broken during mitosis and reforms quickly after mitosis, with the encoded protein first binding HP1 and then attaching to the nuclear lamina. This protein also has been shown to promote MyoD activity and skeletal myogenesis. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Feb 2016]

OMIM ResearchGenerating clinical summary…

LOEUF 0.47

Clinical Summary— PRR14

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.

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ClinVar Variants

83 VUS of 100 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.47LOEUF

pLI 0.169

Z-score 3.69

OE 0.25 (0.14–0.47)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.78Z-score

OE missense 0.89 (0.81–0.97)

333 obs / 375.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.25 (0.14–0.47)

0≤0.351.4

Missense OE?0.89 (0.81–0.97)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 7 / 28.1Missense obs/exp: 333 / 375.8Syn Z: 0.24

ClinVar Variant Classifications

100 submitted variants in ClinVar

ClinVar

Classification Summary

VUS83

Likely Benign4

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	83	83
Likely Benign	4	4
Benign	0	0
Total	87	87

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

View in ClinVar →

11 pathogenic / likely-pathogenic (of 20) ClinVar copy-number / structural variants overlap PRR14 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →