ZFPM1

Chr 16

zinc finger protein, FOG family member 1

Also known as: FOG, FOG1, PRDM18, ZC2HC11A, ZNF89A

NCBI Gene: 161882 ENSG00000179588 UniProt: Q8IX07 OMIM: 601950

The protein functions as a transcription cofactor that forms heterodimers with GATA family transcription factors to regulate gene expression essential for erythroid and megakaryocytic cell differentiation. Mutations cause congenital anemia affecting red blood cell and platelet development, with autosomal recessive inheritance. The gene shows moderate constraint against loss-of-function variants, suggesting some tolerance to protein disruption.

OMIM ResearchSummary from RefSeq, UniProt

Enables RNA polymerase II-specific DNA-binding transcription factor binding activity and transcription corepressor activity. Involved in platelet formation; regulation of definitive erythrocyte differentiation; and regulation of gene expression. Part of transcription repressor complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.47

Clinical Summary— ZFPM1

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Gene-Disease Validity (ClinGen)

congenital heart disease · ADLimited

Limited evidence — not for standalone diagnostic reporting

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 284 VUS of 328 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.47LOEUF

pLI 0.243

Z-score 3.52

OE 0.24 (0.13–0.47)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

-0.05Z-score

OE missense 1.01 (0.93–1.09)

437 obs / 434.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.24 (0.13–0.47)

0≤0.351.4

Missense OE?1.01 (0.93–1.09)

0≤0.61.4

Synonymous OE?1.23

0≤1.21.6

LoF obs/exp: 6 / 25.0Missense obs/exp: 437 / 434.2Syn Z: -2.64

This gene — mechanism propensity

0.4090th %ile

GOF

0.4184th %ile

LOF

0.68top 10%

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

LOFprediction above median · LOEUF 0.47

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

328 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS284

Likely Benign21

Benign4

Pathogenic

284

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	1	0	1
Likely Pathogenic	0	0	0	0
VUS	284	0	0	284
Likely Benign	10	1	10	21
Benign	3	0	1	4
Total	297	2	11	310

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

View in ClinVar →

58 pathogenic / likely-pathogenic (of 81) ClinVar copy-number / structural variants overlap ZFPM1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →