ZNF124

Chr 1

zinc finger protein 124

Also known as: HZF-16, HZF16, ZK7

NCBI Gene: 7678 ENSG00000196418 UniProt: Q15973 OMIM: 194631

The protein is a transcription factor containing a KRAB-A domain and multiple C2H2 zinc finger motifs that regulates gene expression and has anti-apoptotic functions in response to cellular stress. Currently, no human diseases have been definitively associated with ZNF124 mutations. The gene shows low constraint to loss-of-function variation (pLI = 0.01, LOEUF = 1.73), suggesting it may be tolerant to inactivating mutations.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a protein with an amino-terminal KRAB-A box and multiple repeated Kruppel-type (C2H2) zinc finger motifs at its carboxy terminus. The encoded protein may function as a transcription factor. Expression of this gene is increased after vascular endothelial growth factor (VEGF) stimulation in human leukemia cell lines and results in inhibition of apoptotic cell death induced by irradiation or exposure to etoposide. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Jul 2014]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.73

Clinical Summary— ZNF124

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Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

48 VUS of 54 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.73LOEUF

pLI 0.011

Z-score 0.42

OE 0.77 (0.34–1.73)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.16Z-score

OE missense 1.04 (0.91–1.18)

163 obs / 157.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.77 (0.34–1.73)

0≤0.351.4

Missense OE?1.04 (0.91–1.18)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 3 / 3.9Missense obs/exp: 163 / 157.4Syn Z: 0.69

This gene — mechanism propensity

0.77top 25%

GOF

0.77top 25%

LOF

0.3065th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

54 submitted variants in ClinVar

ClinVar

Classification Summary

VUS48

Benign1

VUS

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	2	46	48
Likely Benign	0	0	0
Benign	1	0	1
Total	3	46	49

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

View in ClinVar →

72 pathogenic / likely-pathogenic (of 89) ClinVar copy-number / structural variants overlap ZNF124 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →