GATA2

Chr 3ADSomatic

GATA binding protein 2

Also known as: DCML, IMD21, MONOMAC, NFE1B

NCBI Gene: 2624 ENSG00000179348 UniProt: P23769 OMIM: 137295

This gene encodes a member of the GATA family of zinc-finger transcription factors that are named for the consensus nucleotide sequence they bind in the promoter regions of target genes. The encoded protein plays an essential role in regulating transcription of genes involved in the development and proliferation of hematopoietic and endocrine cell lineages. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Mar 2009]

OMIM Research

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Leukemia, acute myeloid, susceptibility to}MIM #601626

ADSomatic

{Myelodysplastic syndrome, susceptibility to}MIM #614286

Emberger syndromeMIM #614038

Immunodeficiency 21MIM #614172

UniProtLymphedema, primary, with myelodysplasia

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · GATA2 deficiency with susceptibility to MDS/AML · AD · ClinGen 2022

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

280

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.29

LOEUF· LoF intol.

LOF

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.29LOEUF

pLI 0.979

Z-score 3.51

OE 0.06 (0.02–0.29)

Highly constrained

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

Missense Constraint?

2.04Z-score

OE missense 0.67 (0.59–0.75)

195 obs / 293.2 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.06 (0.02–0.29)

0≤0.351.4

Missense OE?0.67 (0.59–0.75)

0≤0.61.4

Synonymous OE?1.16

0≤1.21.6

LoF obs/exp: 1 / 16.3Missense obs/exp: 195 / 293.2Syn Z: -1.40

Background carrier burden — how many people carry a rare variant somewhere in GATA2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 160

598 rare PASS variants

Rare truncating (LoF)

1 in 23,000

13 rare PASS variants

Rare synonymous (reference)

1 in 170

328 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GATA2. 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 21,000
South Asian	~43k	1 in 130	≈ 1 in 21,000
Remaining (unassigned)	~30k	1 in 120	≈ 1 in 29,000
European (Finnish)	~27k	1 in 380	none seen
Admixed American	~22k	1 in 200	none seen
African / African American	~21k	1 in 190	none seen
East Asian	~20k	1 in 120	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 1,200	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 140	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 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓