ZC3H13

Chr 13

zinc finger CCCH-type containing 13

Also known as: KIAA0853, Xio

NCBI Gene: 23091 ENSG00000123200 UniProt: Q5T200

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.

ResearchSummary from RefSeq, UniProt

Enables RNA binding activity. Involved in mRNA processing. Located in nuclear speck. Part of RNA N6-methyladenosine methyltransferase complex. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.21

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.21LOEUF

pLI 1.000

Z-score 8.16

OE 0.13 (0.09–0.21)

Highly constrained

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

Missense Constraint?

1.73Z-score

OE missense 0.84 (0.79–0.89)

741 obs / 885.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.13 (0.09–0.21)

0≤0.351.4

Missense OE?0.84 (0.79–0.89)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 14 / 103.7Missense obs/exp: 741 / 885.8Syn Z: 0.38

Background carrier burden — how many people carry a rare variant somewhere in ZC3H13?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 33

1,972 rare PASS variants

Rare truncating (LoF)

1 in 1,600

152 rare PASS variants

Rare synonymous (reference)

1 in 80

727 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ZC3H13. 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 40	1 in 1,700
South Asian	~43k	1 in 30	1 in 850
Remaining (unassigned)	~30k	1 in 29	1 in 2,100
European (Finnish)	~27k	1 in 82	1 in 780
Admixed American	~22k	1 in 27	1 in 1,600
African / African American	~21k	1 in 33	1 in 1,300
East Asian	~20k	1 in 36	≈ 1 in 4,800
Ashkenazi Jewish	~13k	1 in 130	≈ 1 in 4,300
Middle Eastern	~2,884	1 in 33	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.

Exome coverage (gnomAD): 17 of 18 coding exons well covered in gnomAD exomes; exon 6 marginal. Genomes: all 18.? see exons ↓