ZC3H13

Chr 13

zinc finger CCCH-type containing 13

Also known as: KIAA0853, Xio

ZC3H13 encodes a protein that regulates RNA N6-methyladenosine (m6A) methylation by anchoring components of the methyltransferase complex and bridging WTAP to RNA-binding proteins, playing a critical role in mRNA processing and splicing. The gene is extremely constrained against loss-of-function variants (pLI 1.0, LOEUF 0.21), indicating that mutations are likely to cause severe developmental phenotypes. Clinical reports of pathogenic ZC3H13 variants are limited, but given its essential role in RNA metabolism and embryonic development, mutations would be expected to cause neurodevelopmental disorders with autosomal recessive inheritance.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.21
Clinical SummaryZC3H13
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
55 unique Pathogenic / Likely Pathogenic· 194 VUS of 276 total submissions
Some data sources returned errors (1)

epmc: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.21LOEUF
pLI 1.000
Z-score 8.16
OE 0.13 (0.090.21)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.73Z-score
OE missense 0.84 (0.790.89)
741 obs / 885.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.13 (0.090.21)
00.351.4
Missense OE0.84 (0.790.89)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 14 / 103.7Missense obs/exp: 741 / 885.8Syn Z: 0.38
DN
0.3196th %ile
GOF
0.1699th %ile
LOF
0.84top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.21

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

276 submitted variants in ClinVar

Classification Summary

Pathogenic54
Likely Pathogenic1
VUS194
Likely Benign10
54
Pathogenic
1
Likely Pathogenic
194
VUS
10
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
54
0
54
Likely Pathogenic
0
0
1
0
1
VUS
0
193
1
0
194
Likely Benign
0
6
0
4
10
Benign
0
0
0
0
0
Total0199564259

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

View in ClinVar →

Protein Context — Lollipop Plot

ZC3H13 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found