ZCCHC14

Chr 16

zinc finger CCHC-type containing 14

Also known as: BDG-29, BDG29

NCBI Gene: 23174 ENSG00000140948 UniProt: Q8WYQ9 OMIM: 620697

The ZCCHC14 protein binds nucleic acids, phosphatidylinositol, and zinc ions. Mutations cause autosomal recessive intellectual disability with seizures and brain malformations. This gene is highly constrained against loss-of-function variants (pLI 0.98, LOEUF 0.31), indicating that complete loss of function is likely incompatible with normal development.

OMIM ResearchSummary from RefSeq

Predicted to enable nucleic acid binding activity; phosphatidylinositol binding activity; and zinc ion binding activity. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.31

Clinical Summary— ZCCHC14

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

148 VUS of 186 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.31LOEUF

pLI 0.979

Z-score 4.59

OE 0.15 (0.08–0.31)

Highly constrained

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

Missense Constraint?

0.81Z-score

OE missense 0.91 (0.84–0.97)

531 obs / 586.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.15 (0.08–0.31)

0≤0.351.4

Missense OE?0.91 (0.84–0.97)

0≤0.61.4

Synonymous OE?1.33

0≤1.21.6

LoF obs/exp: 5 / 33.8Missense obs/exp: 531 / 586.4Syn Z: -4.17

This gene — mechanism propensity

0.2997th %ile

GOF

0.3293th %ile

LOF

0.77top 5%

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

LOFprediction above median · LOEUF 0.31

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

186 submitted variants in ClinVar

ClinVar

Classification Summary

VUS148

Likely Benign10

Benign4

148

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	148	0	148
Likely Benign	8	2	10
Benign	2	2	4
Total	158	4	162

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

View in ClinVar →

53 pathogenic / likely-pathogenic (of 74) ClinVar copy-number / structural variants overlap ZCCHC14 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →