ZNF205

Chr 16

zinc finger protein 205

Also known as: RhitH, ZNF210, Zfp13

NCBI Gene: 7755 ENSG00000122386 UniProt: O95201 OMIM: 603436

ZNF205 encodes a transcriptional repressor that regulates MPV17L expression and contributes to hydrogen peroxide metabolism and mitochondrial apoptotic pathways. The gene shows low constraint to loss-of-function variation (pLI = 0.03, LOEUF = 0.56), but no established human disease associations have been reported to date. Clinical significance of ZNF205 variants in pediatric neurological disorders remains to be determined.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II; positive regulation of hydrogen peroxide biosynthetic process; and positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway. Predicted to be located in mitochondrion and nucleus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.56

Clinical Summary— ZNF205

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.

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ClinVar Variants

81 VUS of 97 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.56LOEUF

pLI 0.032

Z-score 3.13

OE 0.30 (0.17–0.56)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.49Z-score

OE missense 0.93 (0.85–1.01)

353 obs / 380.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.30 (0.17–0.56)

0≤0.351.4

Missense OE?0.93 (0.85–1.01)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 7 / 23.3Missense obs/exp: 353 / 380.1Syn Z: -0.94

This gene — mechanism propensity

0.7133th %ile

GOF

0.6932th %ile

LOF

0.4037th %ile

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

DNprediction above median

GOFprediction 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

97 submitted variants in ClinVar

ClinVar

Classification Summary

VUS81

Likely Benign6

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	81	81
Likely Benign	6	6
Benign	0	0
Total	87	87

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

View in ClinVar →

35 pathogenic / likely-pathogenic (of 50) ClinVar copy-number / structural variants overlap ZNF205 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →