PRR14L

Chr 22

proline rich 14 like

Also known as: C22orf30

NCBI Gene: 253143 ENSG00000183530 UniProt: Q5THK1 OMIM: 621035

The PRR14L protein functions in nuclear organization and heterochromatin formation. Mutations cause an autosomal recessive neurodevelopmental disorder characterized by intellectual disability, developmental delay, and seizures. This gene is highly constrained against loss-of-function variants, indicating that complete loss of PRR14L function is typically incompatible with normal development.

OMIM Research

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.28

Clinical Summary— PRR14L

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 271 VUS of 322 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.28LOEUF

pLI 0.997

Z-score 6.25

OE 0.17 (0.10–0.28)

Highly constrained

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

Missense Constraint?

2.47Z-score

OE missense 0.79 (0.75–0.84)

866 obs / 1095.9 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.17 (0.10–0.28)

0≤0.351.4

Missense OE?0.79 (0.75–0.84)

0≤0.61.4

Synonymous OE?0.80

0≤1.21.6

LoF obs/exp: 11 / 65.6Missense obs/exp: 866 / 1095.9Syn Z: 3.22

This gene — mechanism propensity

0.3793th %ile

GOF

0.4874th %ile

LOF

0.74top 10%

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

LOFprediction above median · LOEUF 0.28

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

322 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

VUS271

Likely Benign27

Benign5

Conflicting1

Pathogenic

271

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	2	0	2
Likely Pathogenic	0	0	0	0	0
VUS	0	271	0	0	271
Likely Benign	0	26	0	1	27
Benign	0	4	0	1	5
Conflicting	—				1
Total	0	301	2	2	306

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

View in ClinVar →

20 pathogenic / likely-pathogenic (of 24) ClinVar copy-number / structural variants overlap PRR14L — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →