ZBTB48

Chr 1

zinc finger and BTB domain containing 48

Also known as: HKR3, TZAP, ZNF855, pp9964

NCBI Gene: 3104 ENSG00000204859 UniProt: P10074 OMIM: 165270

The protein directly binds telomeric DNA and regulates telomere length by initiating telomere trimming to prevent accumulation of aberrantly long telomeres, while also functioning as a transcription regulator for genes including the tumor suppressor ARF. Mutations cause autosomal dominant intellectual disability with short stature, behavioral problems, and distinctive facial features. This gene is highly intolerant to loss-of-function mutations, suggesting complete loss of protein function is likely incompatible with normal development.

OMIM ResearchSummary from RefSeq, UniProt

Enables several functions, including identical protein binding activity; sequence-specific DNA binding activity; and zinc ion binding activity. Involved in positive regulation of DNA-templated transcription and telomere maintenance via telomere lengthening. Located in chromosome, telomeric region and nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

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Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.64

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.64LOEUF

pLI 0.000

Z-score 3.07

OE 0.40 (0.25–0.64)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.21Z-score

OE missense 0.83 (0.76–0.91)

348 obs / 417.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.40 (0.25–0.64)

0≤0.351.4

Missense OE?0.83 (0.76–0.91)

0≤0.61.4

Synonymous OE?1.16

0≤1.21.6

LoF obs/exp: 12 / 30.2Missense obs/exp: 348 / 417.3Syn Z: -1.63

Background carrier burden — how many people carry a rare variant somewhere in ZBTB48?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 100

884 rare PASS variants

Rare truncating (LoF)

1 in 2,400

104 rare PASS variants

Rare synonymous (reference)

1 in 76

465 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ZBTB48. 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 150	1 in 2,600
South Asian	~43k	1 in 110	1 in 1,300
Remaining (unassigned)	~30k	1 in 82	1 in 2,900
European (Finnish)	~27k	1 in 550	1 in 1,300
Admixed American	~22k	1 in 120	≈ 1 in 7,000
African / African American	~21k	1 in 85	1 in 1,600
East Asian	~20k	1 in 62	1 in 1,800
Ashkenazi Jewish	~13k	1 in 140	none seen
Middle Eastern	~2,884	1 in 120	≈ 1 in 1,900

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 10 coding exons well covered in gnomAD exomes and genomes.? see exons ↓