ZC3H15

Chr 2

zinc finger CCCH-type containing 15

Also known as: DFRP1, HT010, LEREPO4, MSTP012

NCBI Gene: 55854 ENSG00000065548 UniProt: Q8WU90 OMIM: 619704

The ZC3H15 protein binds RNA and protects DRG1 from degradation while stimulating its GTPase activity. Mutations cause intellectual disability with developmental delay, and the gene shows autosomal recessive inheritance. This gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely detrimental to normal development.

OMIM ResearchSummary from RefSeq, UniProt

Enables RNA binding activity and cadherin binding activity. Involved in positive regulation of GTPase activity. Located in cytosol. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 0.37

Clinical Summary— ZC3H15

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.90). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

31 VUS of 44 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.37LOEUF

pLI 0.903

Z-score 3.61

OE 0.14 (0.07–0.37)

Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.83Z-score

OE missense 0.65 (0.56–0.74)

136 obs / 210.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.14 (0.07–0.37)

0≤0.351.4

Missense OE?0.65 (0.56–0.74)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 3 / 20.7Missense obs/exp: 136 / 210.7Syn Z: 0.26

ClinVar Variant Classifications

44 submitted variants in ClinVar

ClinVar

Classification Summary

VUS31

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	31	31
Likely Benign	1	1
Benign	0	0
Total	32	32

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

View in ClinVar →

26 pathogenic / likely-pathogenic (of 30) ClinVar copy-number / structural variants overlap ZC3H15 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →