LRRC14B

Chr 5

leucine rich repeat containing 14B

NCBI Gene: 389257 ENSG00000185028 UniProt: A6NHZ5

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.

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]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.73

LOEUF

GOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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

Background carrier burden — how many people carry a rare variant somewhere in LRRC14B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 32

804 rare PASS variants

Rare truncating (LoF)

1 in 580

113 rare PASS variants

Rare synonymous (reference)

1 in 150

377 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for LRRC14B. 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 73	1 in 690
South Asian	~43k	1 in 48	1 in 280
Remaining (unassigned)	~30k	1 in 42	1 in 520
European (Finnish)	~27k	1 in 180	1 in 5,200
Admixed American	~22k	1 in 55	1 in 850
African / African American	~21k	1 in 44	1 in 640
East Asian	~20k	1 in 51	1 in 650
Ashkenazi Jewish	~13k	1 in 180	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 44	1 in 440

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): All 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓