ZBTB46

Chr 20

zinc finger and BTB domain containing 46

Also known as: BTBD4, BZEL, RINZF, ZNF340, dJ583P15.7, dJ583P15.8

NCBI Gene: 140685 ENSG00000130584 UniProt: Q86UZ6 OMIM: 614639

ZBTB46 encodes a transcription repressor that regulates dendritic cell differentiation and immune tolerance to gut microbiota. The gene is highly constrained against loss-of-function variants (pLI 0.81, LOEUF 0.40), but no definitive Mendelian disease associations have been established in humans to date.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific; RNA polymerase II transcription regulatory region sequence-specific DNA binding activity; and transcription coregulator activity. Involved in regulation of transcription by RNA polymerase II. Predicted to be located in chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.40

LOEUF

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.40LOEUF

pLI 0.809

Z-score 3.68

OE 0.17 (0.09–0.40)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.24Z-score

OE missense 0.69 (0.63–0.76)

287 obs / 415.2 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.17 (0.09–0.40)

0≤0.351.4

Missense OE?0.69 (0.63–0.76)

0≤0.61.4

Synonymous OE?1.12

0≤1.21.6

LoF obs/exp: 4 / 23.0Missense obs/exp: 287 / 415.2Syn Z: -1.35

Background carrier burden — how many people carry a rare variant somewhere in ZBTB46?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 98

704 rare PASS variants

Rare truncating (LoF)

1 in 7,300

30 rare PASS variants

Rare synonymous (reference)

1 in 120

437 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ZBTB46. 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 120	1 in 9,100
South Asian	~43k	1 in 81	≈ 1 in 21,000
Remaining (unassigned)	~30k	1 in 87	≈ 1 in 15,000
European (Finnish)	~27k	1 in 150	1 in 4,000
Admixed American	~22k	1 in 74	1 in 3,200
African / African American	~21k	1 in 100	1 in 2,200
East Asian	~20k	1 in 86	≈ 1 in 6,600
Ashkenazi Jewish	~13k	1 in 650	none seen
Middle Eastern	~2,884	1 in 67	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): 4 of 4 coding exons well covered in gnomAD exomes. Genomes: 3 of 4 (exon 5 below).? see exons ↓