RSL1D1

Chr 16

ribosomal L1 domain containing 1

Also known as: CSIG, Cic1, L12, PBK1, UTP30

NCBI Gene: 26156 ENSG00000171490 UniProt: O76021 OMIM: 615874

RSL1D1 encodes a protein that binds mRNA and regulates cellular senescence by inhibiting PTEN translation, while also functioning as a pro-apoptotic regulator during DNA damage responses. Mutations cause autosomal recessive developmental delay, seizures, and brain malformations including microcephaly and cortical dysplasia. The gene shows no constraint against loss-of-function variants, consistent with recessive inheritance where heterozygous carriers are unaffected.

OMIM ResearchSummary from RefSeq, UniProt

Enables mRNA 3'-UTR binding activity and mRNA 5'-UTR binding activity. Involved in regulation of apoptotic process and regulation of cellular senescence. Acts upstream of or within regulation of protein localization. Located in several cellular components, including cilium; cytosol; and nucleolus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.00

Clinical Summary— RSL1D1

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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?

1.00LOEUF

pLI 0.000

Z-score 1.54

OE 0.63 (0.41–1.00)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.61Z-score

OE missense 1.29 (1.17–1.41)

325 obs / 252.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.63 (0.41–1.00)

0≤0.351.4

Missense OE?1.29 (1.17–1.41)

0≤0.61.4

Synonymous OE?1.41

0≤1.21.6

LoF obs/exp: 13 / 20.6Missense obs/exp: 325 / 252.9Syn Z: -3.16

This gene — mechanism propensity

0.6162th %ile

GOF

0.3689th %ile

LOF

0.4038th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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.