ZNF407

Chr 18

zinc finger protein 407

Also known as: SIMHA

NCBI Gene: 55628 ENSG00000215421 UniProt: Q9C0G0

This gene encodes a zinc finger protein that may be involved in transcriptional regulation. Mutations cause SIMHA syndrome, which is inherited in an autosomal recessive pattern. The gene is highly constrained against loss-of-function variants (pLI >0.99, LOEUF 0.092), indicating it is critical for normal cellular function.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a zinc finger protein whose exact function is not known. It may be involved in transcriptional regulation. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.09

Clinical Summary— ZNF407

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 392 VUS of 555 total submissions

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.09LOEUF

pLI 1.000

Z-score 7.44

OE 0.03 (0.01–0.09)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

0.86Z-score

OE missense 0.93 (0.89–0.98)

1173 obs / 1258.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.03 (0.01–0.09)

0≤0.351.4

Missense OE?0.93 (0.89–0.98)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

LoF obs/exp: 2 / 68.4Missense obs/exp: 1173 / 1258.8Syn Z: -2.20

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

limitedZNF407-related neurodevelopmental disorderOTHERAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.3594th %ile

GOF

0.2696th %ile

LOF

0.74top 10%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

555 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

VUS392

Likely Benign110

Benign26

Conflicting16

Pathogenic

392

VUS

110

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	2	0	0	2
Likely Pathogenic	0	0	0	0	0
VUS	5	371	3	13	392
Likely Benign	0	37	4	69	110
Benign	0	9	0	17	26
Conflicting	—				16
Total	5	419	7	99	546

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

View in ClinVar →

155 pathogenic / likely-pathogenic (of 183) ClinVar copy-number / structural variants overlap ZNF407 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →