C18ORF21

Chr 18

ribonuclease MRP subunit p24

Also known as: C18orf21, HsT3108, PNAS-124, PNAS-131, XTP13

NCBI Gene: 83608 ENSG00000141428 UniProt: Q32NC0 OMIM: 621218

This protein is a specific component of the MRP ribonucleoprotein endoribonuclease complex that processes precursor ribosomal RNA. Mutations cause autosomal recessive primary microcephaly, typically presenting in infancy with severe intellectual disability and growth retardation. The gene shows low constraint against loss-of-function variants, which is consistent with the recessive inheritance pattern observed in affected families.

OMIM ResearchSummary from UniProt

Predicted to enable RNA binding activity. Involved in RNA processing. Located in nucleus. Part of ribonuclease MRP complex. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.55

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.55LOEUF

pLI 0.000

Z-score 0.23

OE 0.92 (0.57–1.55)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.30Z-score

OE missense 0.92 (0.79–1.08)

106 obs / 115.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.92 (0.57–1.55)

0≤0.351.4

Missense OE?0.92 (0.79–1.08)

0≤0.61.4

Synonymous OE?0.79

0≤1.21.6

LoF obs/exp: 10 / 10.8Missense obs/exp: 106 / 115.1Syn Z: 1.08

Background carrier burden — how many people carry a rare variant somewhere in C18ORF21?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 290

290 rare PASS variants

Rare truncating (LoF)

1 in 2,700

64 rare PASS variants

Rare synonymous (reference)

1 in 880

98 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for C18ORF21. 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 610	1 in 2,600
South Asian	~43k	1 in 170	1 in 1,200
Remaining (unassigned)	~30k	1 in 350	1 in 4,300
European (Finnish)	~27k	1 in 2,400	none seen
Admixed American	~22k	1 in 300	1 in 2,800
African / African American	~21k	1 in 230	1 in 1,700
East Asian	~20k	1 in 190	1 in 2,000
Ashkenazi Jewish	~13k	≈ 1 in 6,500	none seen
Middle Eastern	~2,884	1 in 580	none seen

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.