ZNF148

Chr 3AD

zinc finger protein 148

Also known as: BERF-1, BFCOL1, GDACCF, HT-BETA, ZBP-89, ZFP148, pHZ-52

NCBI Gene: 7707ENSG00000163848UniProt: Q9UQR1OMIM: 601897

ZNF148 encodes a Kruppel family zinc finger transcription factor that activates transcription of T-cell receptor and intestinal alkaline phosphatase genes while repressing transcription of ornithine decarboxylase, vimentin, gastrin, stromelysin, and enolase genes. Mutations cause global developmental delay with hypoplastic corpus callosum and dysmorphic facies, following an autosomal dominant inheritance pattern. This gene is highly constrained against loss-of-function variants (pLI = 1.00, LOEUF = 0.10), indicating that haploinsufficiency is likely not tolerated in the general population.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismADLOEUF 0.101 OMIM phenotype
Clinical Summary— ZNF148
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
41 unique Pathogenic / Likely Pathogenic· 105 VUS of 191 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.10LOEUF
pLI 1.000
Z-score 4.99
OE 0.00 (0.00–0.10)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
3.52Z-score
OE missense 0.51 (0.46–0.58)
213 obs / 414.5 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.00 (0.00–0.10)
0≤0.351.4
Missense OE0.51 (0.46–0.58)
0≤0.61.4
Synonymous OE1.01
0≤1.21.6
LoF obs/exp: 0 / 29.0Missense obs/exp: 213 / 414.5Syn Z: -0.10
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongZNF148-related neurodevelopmental disorderLOFAD
DN
0.2399th %ile
GOF
0.2398th %ile
LOF
0.87top 5%

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

LOFprediction above median · 54% of P/LP variants are LoF · LOEUF 0.10

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

191 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic20
VUS105
Likely Benign19
Benign7
Conflicting2
21
Pathogenic
20
Likely Pathogenic
105
VUS
19
Likely Benign
7
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
1
14
0
21
Likely Pathogenic
16
3
1
0
20
VUS
10
80
15
0
105
Likely Benign
0
7
1
11
19
Benign
0
0
3
4
7
Conflicting
—2
Total32913415174

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

View in ClinVar →

Protein Context — Lollipop Plot

ZNF148 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients