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…

Primary Disease Associations & Inheritance

Global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic faciesMIM #617260

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies; no ClinGen or GenCC tier

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.10

LOEUF· LoF intol.

LOF

Mechanism· G2P

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

Background carrier burden — how many people carry a rare variant somewhere in ZNF148?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 100

638 rare PASS variants

Rare truncating (LoF)

1 in 3,700

23 rare PASS variants

Rare synonymous (reference)

1 in 120

361 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ZNF148. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 140	1 in 5,600
South Asian	~43k	1 in 140	1 in 5,800
Remaining (unassigned)	~30k	1 in 150	1 in 810
European (Finnish)	~27k	1 in 440	1 in 1,600
Admixed American	~22k	1 in 100	1 in 1,100
African / African American	~21k	1 in 180	1 in 1,100
East Asian	~20k	1 in 170	1 in 2,300
Ashkenazi Jewish	~13k	1 in 430	≈ 1 in 3,300
Middle Eastern	~2,884	1 in 280	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓