ZNF236

Chr 18

zinc finger protein 236

Also known as: ZNF236A, ZNF236B

NCBI Gene: 7776 ENSG00000130856 UniProt: Q9UL36 OMIM: 604760

ZNF236 encodes a DNA-binding transcription factor that regulates RNA polymerase II transcription and is involved in cellular glucose response. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability and developmental delay. This gene is highly constrained against loss-of-function variants, indicating that such mutations are likely pathogenic when they occur.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in cellular response to glucose stimulus. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

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

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.17

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.17LOEUF

pLI 1.000

Z-score 7.75

OE 0.09 (0.05–0.17)

Highly constrained

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

Missense Constraint?

3.84Z-score

OE missense 0.67 (0.63–0.72)

743 obs / 1101.2 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.09 (0.05–0.17)

0≤0.351.4

Missense OE?0.67 (0.63–0.72)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 8 / 85.2Missense obs/exp: 743 / 1101.2Syn Z: -0.16

Background carrier burden — how many people carry a rare variant somewhere in ZNF236?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 37

1,954 rare PASS variants

Rare truncating (LoF)

1 in 470

94 rare PASS variants

Rare synonymous (reference)

1 in 34

978 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ZNF236. 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 40	1 in 320
South Asian	~43k	1 in 37	1 in 1,300
Remaining (unassigned)	~30k	1 in 30	1 in 1,300
European (Finnish)	~27k	1 in 89	1 in 2,400
Admixed American	~22k	1 in 32	1 in 1,400
African / African American	~21k	1 in 35	1 in 2,000
East Asian	~20k	1 in 44	1 in 400
Ashkenazi Jewish	~13k	1 in 190	none seen
Middle Eastern	~2,884	1 in 36	≈ 1 in 2,100

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): 30 of 31 coding exons well covered in gnomAD exomes; exon 1 poorly covered. Genomes: 30 of 31 (exon 1 below).? see exons ↓