ZNF148

Chr 3AD

zinc finger protein 148

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

NCBI Gene: 7707 ENSG00000163848 UniProt: Q9UQR1 OMIM: 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.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a member of the Kruppel family of zinc finger DNA binding proteins. The encoded protein activates transcription of the T-cell receptor and intestinal alkaline phosphatase genes but represses transcription of the ornithine decarboxylase, vimentin, gastrin, stomelysin, and enolase genes. Increased expression of this gene results in decreased patient survival rates from colorectal cancer, while mutations in this gene have been associated with global developmental delay, hypoplastic corpus callosum, and dysmorphic facies. [provided by RefSeq, Feb 2017]

OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.101 OMIM phenotype

Clinical Summary— ZNF148

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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.

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ClinVar Variants

27 unique Pathogenic / Likely Pathogenic· 94 VUS of 166 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 OE?0.00 (0.00–0.10)

0≤0.351.4

Missense OE?0.51 (0.46–0.58)

0≤0.61.4

Synonymous OE?1.01

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

This gene — mechanism propensity

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 · 85% 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

166 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7

Likely Pathogenic20

VUS94

Likely Benign19

Benign7

Conflicting2

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	6	1	0	0	7
Likely Pathogenic	17	3	0	0	20
VUS	10	80	4	0	94
Likely Benign	0	7	1	11	19
Benign	0	0	3	4	7
Conflicting	—				2
Total	33	91	8	15	149

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

View in ClinVar →

15 pathogenic / likely-pathogenic (of 26) ClinVar copy-number / structural variants overlap ZNF148 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →