KIDINS220

Chr 2ADAR

kinase D interacting substrate 220

Also known as: ARMS, SINO, VENARG

This gene encodes a transmembrane scaffold protein that controls neuronal survival, differentiation, and synaptic plasticity by mediating crosstalk between neurotrophin signaling and other intracellular pathways, including sustained ERK activation through Rap1-dependent mechanisms. Mutations cause a neurodevelopmental syndrome characterized by spastic paraplegia, intellectual disability, nystagmus, and obesity, as well as ventriculomegaly and arthrogryposis, with both autosomal dominant and autosomal recessive inheritance patterns reported.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAD/ARLOEUF 0.352 OMIM phenotypes
Clinical SummaryKIDINS220
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Gene-Disease Validity (ClinGen)
spastic paraplegia, intellectual disability, nystagmus, and obesity · ADModerate

Moderate evidence — consider for supplementary testing

2 total gene-disease associations curated

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.35LOEUF
pLI 0.074
Z-score 6.41
OE 0.24 (0.170.35)
Highly constrained

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

Missense Constraint
2.26Z-score
OE missense 0.80 (0.750.84)
780 obs / 979.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.24 (0.170.35)
00.351.4
Missense OE0.80 (0.750.84)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 20 / 83.0Missense obs/exp: 780 / 979.1Syn Z: 0.22

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

KIDINS220 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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