RCL1

Chr 9

RNA terminal phosphate cyclase like 1

Also known as: RNAC, RPCL1

NCBI Gene: 10171 ENSG00000120158 UniProt: Q9Y2P8 OMIM: 611405

The RCL1 protein functions as an RNA endonuclease that is essential for ribosomal small subunit biogenesis, specifically in the early pre-rRNA processing steps required for proper 18S RNA maturation. Mutations cause autosomal recessive developmental delay with variable intellectual disability and dysmorphic features. This gene shows moderate constraint against loss-of-function variants, suggesting that complete loss of function is not well-tolerated during development.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable RNA endonuclease activity. Involved in ribosomal small subunit biogenesis. Part of small-subunit processome. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 0.57

Clinical Summary— RCL1

⚡

Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.

📋

ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 62 VUS of 80 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.57LOEUF

pLI 0.059

Z-score 2.98

OE 0.29 (0.16–0.57)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

-1.05Z-score

OE missense 1.20 (1.08–1.33)

258 obs / 214.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.29 (0.16–0.57)

0≤0.351.4

Missense OE?1.20 (1.08–1.33)

0≤0.61.4

Synonymous OE?1.29

0≤1.21.6

LoF obs/exp: 6 / 20.6Missense obs/exp: 258 / 214.7Syn Z: -2.08

ClinVar Variant Classifications

80 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS62

Likely Benign2

Benign2

Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	1	0	0	1
Likely Pathogenic	0	0	0	0
VUS	0	62	0	62
Likely Benign	0	1	1	2
Benign	0	1	1	2
Total	1	64	2	67

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

View in ClinVar →

170 pathogenic / likely-pathogenic (of 185) ClinVar copy-number / structural variants overlap RCL1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →