ZNF35

Chr 3

zinc finger protein 35

Also known as: HF.10, HF10, Zfp105

The ZNF35 protein functions as a DNA-binding transcription factor that regulates gene expression and is involved in cell differentiation and proliferation. Mutations in this gene have been associated with neurodevelopmental disorders, though the specific phenotypic spectrum and inheritance pattern require further clinical characterization. The gene shows tolerance to loss-of-function variants (low constraint), suggesting that haploinsufficiency may not be the primary disease mechanism in associated disorders.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.60
Clinical SummaryZNF35
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.
📋
ClinVar Variants
6 unique Pathogenic / Likely Pathogenic· 67 VUS of 73 total submissions
Some data sources returned errors (1)

opentargets: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.60LOEUF
pLI 0.042
Z-score 2.85
OE 0.31 (0.170.60)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.36Z-score
OE missense 0.77 (0.690.86)
212 obs / 275.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.31 (0.170.60)
00.351.4
Missense OE0.77 (0.690.86)
00.61.4
Synonymous OE1.08
01.21.6
LoF obs/exp: 6 / 19.6Missense obs/exp: 212 / 275.5Syn Z: -0.61
DN
0.83top 10%
GOF
0.7028th %ile
LOF
0.3259th %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

73 submitted variants in ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic1
VUS67
5
Pathogenic
1
Likely Pathogenic
67
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
0
0
1
0
1
VUS
0
65
2
0
67
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total0658073

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

View in ClinVar →

Protein Context — Lollipop Plot

ZNF35 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC