ZBTB37

Chr 1

zinc finger and BTB domain containing 37

Also known as: D430004I08Rik, ZNF908

NCBI Gene: 84614 ENSG00000185278 UniProt: Q5TC79

The ZBTB37 protein is a transcriptional regulator that binds DNA and is predicted to negatively regulate RNA polymerase II transcription and immune system processes. This gene is highly constrained against loss-of-function variants (pLI 0.96, LOEUF 0.34), suggesting that mutations would likely cause severe developmental disorders, though specific associated diseases have not yet been established. The inheritance pattern for ZBTB37-related disorders has not been determined.

ResearchSummary from RefSeq, UniProt

Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II; regulation of cytokine production; and regulation of immune system process. Predicted to be located in chromatin. Predicted to be active in nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.34

Clinical Summary— ZBTB37

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.96). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

3 unique Pathogenic / Likely Pathogenic· 46 VUS of 52 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.34LOEUF

pLI 0.955

Z-score 3.56

OE 0.11 (0.04–0.34)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.36Z-score

OE missense 0.61 (0.54–0.69)

182 obs / 296.0 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.11 (0.04–0.34)

0≤0.351.4

Missense OE?0.61 (0.54–0.69)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 2 / 18.5Missense obs/exp: 182 / 296.0Syn Z: -0.33

This gene — mechanism propensity

0.4289th %ile

GOF

0.3391th %ile

LOF

0.69top 10%

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

LOFprediction above median · LOEUF 0.34

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

52 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

VUS46

Pathogenic

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	3	3
Likely Pathogenic	0	0	0
VUS	46	0	46
Likely Benign	0	0	0
Benign	0	0	0
Total	46	3	49

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

View in ClinVar →

44 pathogenic / likely-pathogenic (of 52) ClinVar copy-number / structural variants overlap ZBTB37 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →