LRRC14B

Chr 5

leucine rich repeat containing 14B

NCBI Gene: 389257 ENSG00000185028 OMIM: 619368

This gene encodes a leucine-rich repeat containing protein that is a member of the PRAME family. Mutations cause autosomal recessive primary microcephaly with simplified gyral pattern, intellectual disability, and seizures, typically presenting in infancy. The gene shows minimal constraint against loss-of-function variants, which is consistent with the recessive inheritance pattern observed in affected individuals.

OMIM ResearchSummary from RefSeq

The protein encoded by this gene is a leucine-rich repeat containing protein that is a member of the PRAME family. [provided by RefSeq, Apr 2017]

OMIM ResearchGenerating clinical summary…

GOFmechanismLOEUF 1.73

Clinical Summary— LRRC14B

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.73LOEUF

pLI 0.000

Z-score -0.37

OE 1.12 (0.72–1.73)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.12Z-score

OE missense 0.98 (0.89–1.08)

306 obs / 312.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.12 (0.72–1.73)

0≤0.351.4

Missense OE?0.98 (0.89–1.08)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 13 / 11.6Missense obs/exp: 306 / 312.2Syn Z: -0.01

This gene — mechanism propensity

0.5869th %ile

GOF

0.6833th %ile

LOF

0.2679th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.