C21ORF58

Chr 21

chromosome 21 open reading frame 58

This gene encodes a protein of unknown function. Biallelic mutations cause autosomal recessive intellectual disability with microcephaly, seizures, and spasticity, typically presenting in early childhood. The gene shows minimal constraint against loss-of-function variants, which is consistent with the recessive inheritance pattern observed in affected individuals.

0
Active trials
1
Pubs (1 yr)
100
P/LP submissions
P/LP missense
1.70
LOEUF
Mechanism
Clinical SummaryC21ORF58
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
94 unique Pathogenic / Likely Pathogenic· 26 VUS of 136 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.70LOEUF
pLI 0.000
Z-score -0.53
OE 1.15 (0.781.70)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.35Z-score
OE missense 0.92 (0.811.06)
152 obs / 164.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.15 (0.781.70)
00.351.4
Missense OE0.92 (0.811.06)
00.61.4
Synonymous OE1.23
01.21.6
LoF obs/exp: 17 / 14.8Missense obs/exp: 152 / 164.7Syn Z: -1.48

ClinVar Variant Classifications

136 submitted variants in ClinVar

Classification Summary

Pathogenic86
Likely Pathogenic8
VUS26
Likely Benign2
Benign1
Conflicting1
86
Pathogenic
8
Likely Pathogenic
26
VUS
2
Likely Benign
1
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
86
Likely Pathogenic
8
VUS
26
Likely Benign
2
Benign
1
Conflicting
1
Total124

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

C21ORF58 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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