ZNF407

Chr 18AR

zinc finger protein 407

Also known as: SIMHA

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.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

SIMHA syndromeMIM #619557
AR
UniProtShort stature, impaired intellectual development, microcephaly, hypotonia, and ocular anomalies
0
Active trials
1
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.09
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryZNF407
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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.09LOEUF
pLI 1.000
Z-score 7.44
OE 0.03 (0.010.09)
Highly constrained

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

Missense Constraint
0.86Z-score
OE missense 0.93 (0.890.98)
1173 obs / 1258.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.03 (0.010.09)
00.351.4
Missense OE0.93 (0.890.98)
00.61.4
Synonymous OE1.13
01.21.6
LoF obs/exp: 2 / 68.4Missense obs/exp: 1173 / 1258.8Syn Z: -2.20
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedZNF407-related neurodevelopmental disorderOTHERAR

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

DN
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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ZNF407 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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