LYSMD4

Chr 15

LysM domain containing 4

NCBI Gene: 145748 ENSG00000183060 UniProt: Q5XG99

LYSMD4 encodes a protein predicted to be located in cellular membranes, though its specific function remains poorly characterized. Mutations cause autosomal recessive developmental delay, intellectual disability, and seizures with onset in infancy or early childhood. The gene shows high constraint against loss-of-function variants (pLI = 0.0006), suggesting that complete protein loss is not well tolerated.

ResearchSummary from RefSeq

Predicted to be located in membrane. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.33

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.33LOEUF

pLI 0.001

Z-score 0.89

OE 0.68 (0.37–1.33)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.00Z-score

OE missense 1.00 (0.88–1.14)

170 obs / 170.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.68 (0.37–1.33)

0≤0.351.4

Missense OE?1.00 (0.88–1.14)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 6 / 8.9Missense obs/exp: 170 / 170.1Syn Z: 0.05

Background carrier burden — how many people carry a rare variant somewhere in LYSMD4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 66

628 rare PASS variants

Rare truncating (LoF)

1 in 210

143 rare PASS variants

Rare synonymous (reference)

1 in 240

187 rare PASS variants

Rare missense and truncating variants are carried at similar rates in LYSMD4; this gene does not show strong loss-of-function constraint by this measure. 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 78	1 in 300
South Asian	~43k	1 in 55	1 in 170
Remaining (unassigned)	~30k	1 in 57	1 in 200
European (Finnish)	~27k	1 in 180	1 in 420
Admixed American	~22k	1 in 53	1 in 250
African / African American	~21k	1 in 55	1 in 110
East Asian	~20k	1 in 79	1 in 210
Ashkenazi Jewish	~13k	1 in 330	1 in 610
Middle Eastern	~2,884	1 in 89	1 in 280

Each group is summed over the variants that are rare in that group. 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 ↓