ARMH4

Chr 14

armadillo like helical domain containing 4

Also known as: C14orf37, UT2, c14_5376

The protein modulates immune responses by down-regulating STAT3 signaling through direct interaction with IL6ST and may negatively regulate AKT signaling by modulating mTORC2 complex activity. Mutations in this gene cause neurodevelopmental disorders with immune dysfunction, typically following an autosomal recessive inheritance pattern. The gene shows tolerance to loss-of-function variants, suggesting that complete protein loss may be required for disease manifestation.

ResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.88
Clinical SummaryARMH4
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.88LOEUF
pLI 0.000
Z-score 2.02
OE 0.57 (0.380.88)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.07Z-score
OE missense 1.01 (0.931.09)
409 obs / 405.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.57 (0.380.88)
00.351.4
Missense OE1.01 (0.931.09)
00.61.4
Synonymous OE1.12
01.21.6
LoF obs/exp: 15 / 26.2Missense obs/exp: 409 / 405.2Syn Z: -1.13
DN
0.6841th %ile
GOF
0.5072th %ile
LOF
0.3551th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ARMH4 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

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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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC